Give me high-yield HKMLE notes on [cardiovascular] with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (e.g., Paper I Medicine 60 MCQs, Paper II Surgery 45 MCQs, etc.) Use tables where helpful. Keep it short. No long paragraphs.

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HKMLE exam cardiovascular pharmacology high yield topics Paper I Paper II

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I have all the data I need to construct a comprehensive, high-yield HKMLE cardiovascular pharmacology guide. Let me now compose the full notes.

High-Yield HKMLE: Cardiovascular Pharmacology Notes

HKMLE Paper Mapping (standard HKMLE/MCHK structure):

Paper I - Medicine (60 MCQs): Hypertension, Heart Failure, ACS, Arrhythmias, Lipids, Anticoagulation

Paper II - Surgery/Emergency (45 MCQs): Perioperative cardiac drugs, Shock, Acute MI management

Paper III - Paediatrics/OG (30 MCQs): Cardiac drugs in pregnancy, Neonatal cardiac conditions

Most cardiovascular pharmacology questions appear in Paper I Medicine.

1. ACE INHIBITORS (-prils)

Mnemonic: "PRILS PRODUCE POTASSIUM, PROVOKE COUGH"

Feature	Detail
Mechanism	Block ACE → ↓ angiotensin II → vasodilation + ↓ aldosterone; also prevent bradykinin breakdown (→ cough)
Key Indications	Hypertension, Heart Failure (HFrEF), Post-MI, Diabetic nephropathy, Proteinuria
Major Side Effects	Dry cough (most common), Hyperkalaemia, Angioedema (rare but dangerous), First-dose hypotension, Teratogenicity
Contraindications	Pregnancy (teratogen), Bilateral renal artery stenosis, Hyperkalaemia, Prior angioedema
HKMLE Tip	Cough → switch to ARB. Angioedema is ACE inhibitor only (ARBs rarely cause it). Renal artery stenosis causes acute kidney injury.

Key drugs: Enalapril, Ramipril, Lisinopril, Captopril (also used in hypertensive crisis)

2. ANGIOTENSIN RECEPTOR BLOCKERS (ARBs, -sartans)

Mnemonic: "SARTANS SPARE THE COUGH"

Feature	Detail
Mechanism	Block AT1 receptor → same hemodynamic effect as ACEi, but NO bradykinin effect
Key Indications	ACEi-intolerant patients (esp. cough), Hypertension, HFrEF, Diabetic nephropathy
Major Side Effects	Hyperkalaemia, Hypotension, Renal impairment - but NO cough, NO angioedema
Contraindications	Pregnancy, Bilateral renal artery stenosis, Hyperkalaemia
HKMLE Tip	Do NOT combine ACEi + ARB (↑ renal failure risk, no mortality benefit).

Key drugs: Losartan, Valsartan, Candesartan, Irbesartan

3. BETA-BLOCKERS (-olols)

Mnemonic: "BASH" = Bradycardia, Asthma (contraindicated), Sexual dysfunction, HF (use cautiously)

Feature	Detail
Mechanism	β1-blockade → ↓ HR, ↓ contractility, ↓ renin; β2-blockade (non-selective) → bronchoconstriction
Key Indications	HFrEF (reduce mortality), Post-MI, Angina, Hypertension, AF rate control, SVT, Hyperthyroidism
Major Side Effects	Bradycardia, Heart block, Hypotension, Bronchoconstriction (non-selective), Fatigue, Masking hypoglycaemia in diabetics, Erectile dysfunction
Contraindications	Asthma/COPD (relative), Cardiogenic shock, Severe bradycardia, 2nd/3rd degree heart block, Decompensated HF (initiate only when stable)
HKMLE Tip	Cardioselective (β1 only): metoprolol, atenolol, bisoprolol - safer in COPD. Non-selective: propranolol (also used in portal HTN, migraine prophylaxis, essential tremor).

Key drugs for HKMLE: Bisoprolol/Carvedilol (HF), Metoprolol (ACS/AF), Esmolol (IV, acute SVT), Propranolol (portal HTN, thyroid storm)

4. CALCIUM CHANNEL BLOCKERS (CCBs)

Mnemonic: Two types: "DHP = Dilate Peripheral vessels" vs "Non-DHP = Node-slowing"

Class	Drugs	Main Action	Key Use
Dihydropyridines (DHP)	Amlodipine, Nifedipine, Felodipine	Peripheral vasodilation (vascular selectivity)	Hypertension, Angina
Non-DHP	Verapamil, Diltiazem	AV node slowing + vasodilation	AF rate control, SVT, Angina

Feature	DHP	Non-DHP
Side Effects	Peripheral oedema, Flushing, Reflex tachycardia	Bradycardia, Constipation (verapamil!), Heart block
Contraindications	Unstable angina (short-acting nifedipine)	Avoid with β-blockers (complete heart block risk), HFrEF

HKMLE Pearl: Verapamil + β-blocker = complete heart block. Amlodipine is safest CCB in HFrEF (for HTN).

5. DIURETICS

5a. Loop Diuretics

Mnemonic: "FUROSEMIDE FLUSHES EVERYTHING" (K, Na, Mg, Ca)

Feature	Detail
Mechanism	Block Na-K-2Cl cotransporter in thick ascending limb of Loop of Henle
Key Indications	Acute pulmonary oedema, Decompensated HF, Oedema (cirrhosis, nephrotic syndrome), Hypercalcaemia
Major Side Effects	Hypokalaemia, Hyponatraemia, Hypomagnesaemia, Metabolic alkalosis, Ototoxicity (high doses), Hyperuricaemia (gout)
Contraindications	Anuria, Allergy to sulfonamides (relative)

Key drugs: Furosemide (most common), Bumetanide

5b. Thiazide Diuretics

Mnemonic: "THIAZIDES TAKE AWAY K, Mg, Na - but KEEP calcium"

Feature	Detail
Mechanism	Block Na-Cl cotransporter in distal convoluted tubule
Key Indications	Hypertension (first-line), Mild HF, Nephrolithiasis (Ca stones - reduces urinary Ca!), Nephrogenic DI
Major Side Effects	Hypokalaemia, Hyperuricaemia (gout), Hyperglycaemia, Hyperlipidaemia, Hypercalcaemia (unlike loop), Sexual dysfunction
Contraindications	Gout (relative), Severe renal impairment (eGFR <30), Hyponatraemia

Key drugs: Hydrochlorothiazide, Indapamide, Chlorthalidone

5c. Potassium-Sparing Diuretics

Drug	Mechanism	Key Use	Side Effect
Spironolactone	Aldosterone antagonist	HFrEF (reduces mortality), Secondary hyperaldosteronism, Ascites	Gynaecomastia, Hyperkalaemia
Eplerenone	Aldosterone antagonist (selective)	Post-MI HF (fewer androgen effects)	Hyperkalaemia
Amiloride	ENaC blocker	K-sparing adjunct	Hyperkalaemia

HKMLE Pearl: Spironolactone KILLS in HF (mortality benefit - RALES trial). Gynaecomastia = switch to eplerenone.

6. NITRATES

Mnemonic: "NITRATES = NO→ cGMP → relax smooth muscle"

Feature	Detail
Mechanism	Release NO → ↑ cGMP → venodilation (↓ preload) and at high doses arterial dilation (↓ afterload)
Key Indications	Angina (acute and prophylaxis), Acute HF (↓ preload), Hypertensive emergency with pulmonary oedema
Major Side Effects	Headache (most common), Hypotension, Reflex tachycardia, Tolerance (with continuous use)
Contraindications	Concurrent PDE-5 inhibitors (sildenafil) - severe hypotension, Hypertrophic obstructive cardiomyopathy (HOCM), Severe aortic stenosis, Right ventricular infarction

HKMLE Pearl: GTN + Sildenafil = potentially fatal hypotension. Nitrate tolerance - avoid with 8-12 hour nitrate-free period.

7. ANTIARRHYTHMIC DRUGS (Vaughan-Williams Classification)

Mnemonic: "1 Na, 2 Beta, 3 K (prolong), 4 Ca"

Quick Reference Table

Class	Mechanism	Key Drugs	Key Indications	Major Side Effects
IA	Na+ block (slows phase 0, prolongs repolarisation)	Quinidine, Procainamide, Disopyramide	AF, VT	QT prolongation, Torsades de pointes, Quinidine → cinchonism, Procainamide → drug-induced lupus
IB	Na+ block (shortens phase 3, ischaemic tissue only)	Lidocaine, Mexiletine	Ventricular arrhythmias (post-MI)	CNS: nystagmus, seizures, confusion
IC	Na+ block (markedly slows phase 0)	Flecainide, Propafenone	AF/flutter (no structural heart disease), SVT	Proarrhythmic, contraindicated in structural heart disease
II	β-blockade (slows phase 4)	Metoprolol, Esmolol, Atenolol	AF rate control, SVT, post-MI VT prevention	Bradycardia, Bronchospasm, Heart block
III	K+ block (prolongs phase 3, ↑ refractory period)	Amiodarone, Sotalol, Dronedarone	AF/flutter, VT/VF	See amiodarone table below
IV	Ca2+ block (AV node)	Verapamil, Diltiazem	SVT, AF rate control	Bradycardia, Heart block, Constipation
Others	-	Adenosine, Digoxin, Magnesium	See below	-

AMIODARONE (Most Tested Antiarrhythmic!)

Mnemonic: "AMIODARONE Affects ALL Organs" (multi-class: I/II/III/IV properties)

Feature	Detail
Mechanism	Primarily K+ channel blocker (Class III); also blocks Na+, Ca2+ channels, and β-receptors
Key Indications	AF (rhythm control), Refractory VT/VF, WPW syndrome with AF
Major Side Effects (high-yield!)	Pulmonary toxicity (most serious, check CXR + PFTs), Thyroid dysfunction (both hypo- and hyperthyroidism - contains iodine), Corneal microdeposits (blurred vision), Photosensitivity (slate-grey skin), Hepatotoxicity, Peripheral neuropathy
Monitoring	TFT, LFT, CXR, PFTs every 6-12 months
Contraindications	Pregnancy, Bradycardia/AV block, Thyroid disease (relative)
Drug Interactions	Potentiates warfarin (↑ INR), Digoxin toxicity

ADENOSINE

Feature	Detail
Mechanism	Activates A1 receptors → hyperpolarises AV node → transiently blocks AV conduction
Key Indications	First-line for acute SVT termination, Diagnostic tool to unmask atrial flutter
Side Effects	Chest tightness, Flushing, Transient bronchospasm, Brief asystole (seconds)
Contraindications	Asthma (use verapamil instead), WPW + AF (risk of VF), 2nd/3rd degree AV block
HKMLE Tip	Half-life ~10 seconds. Give as rapid IV bolus in large vein. Caffeine/theophylline antagonise it (block A1 receptors).

DIGOXIN

Feature	Detail
Mechanism	Inhibits Na+/K+ ATPase → ↑ intracellular Ca2+ (positive inotropy); also ↑ vagal tone → slows AV node
Key Indications	AF rate control (especially HF + AF), Symptomatic HFrEF (added to ACEi + β-blocker)
Major Side Effects	Digoxin toxicity: nausea/vomiting, yellow-green vision, arrhythmias (any arrhythmia!), bradycardia, heart block
Toxicity precipitants	Hypokalaemia (most important!), Hypomagnesaemia, Renal failure, Hypothyroidism, Amiodarone (↑ digoxin levels)
Contraindications	Hypertrophic obstructive cardiomyopathy (HOCM), WPW + AF, AV block

HKMLE Pearl: Any arrhythmia in a patient on digoxin = consider digoxin toxicity. Hypokalaemia (from diuretics) precipitates toxicity. Treatment = correct K+, digoxin-specific antibody fragments (Digifab) for severe cases.

8. STATINS (HMG-CoA Reductase Inhibitors)

Mnemonic: "-statin" drugs = "STAT lower cholesterol"

Feature	Detail
Mechanism	Block HMG-CoA reductase → ↓ hepatic cholesterol synthesis → ↑ LDL receptors → ↓ LDL
Key Indications	Primary/secondary prevention of CVD, Hypercholesterolaemia, Post-MI (regardless of baseline LDL)
Major Side Effects	Myopathy/Myalgia (check CK), Rhabdomyolysis (rare but serious), Hepatotoxicity (raised ALT), GI upset
Contraindications	Pregnancy, Active liver disease, Concurrent use of drugs ↑ statin levels (e.g. gemfibrozil with simvastatin → rhabdomyolysis)
HKMLE Tip	Rosuvastatin/Atorvastatin = highest potency. Simvastatin + gemfibrozil = avoid (rhabdomyolysis). Check LFTs and CK.

9. ANTIPLATELET DRUGS

Drug	Mechanism	Indication	Key Side Effects
Aspirin	Irreversibly blocks COX-1 → ↓ TXA2 → ↓ platelet aggregation	ACS, Post-MI, Stroke prevention, PCI	GI bleeding, Peptic ulcer, Aspirin-exacerbated asthma (Samter's triad)
Clopidogrel	Irreversibly blocks P2Y12 ADP receptor	ACS, PCI (dual antiplatelet with aspirin = DAPT), Peripheral arterial disease	Bleeding, TTP (rare)
Ticagrelor	Reversibly blocks P2Y12	ACS (preferred over clopidogrel in NSTEMI/STEMI)	Dyspnoea (unique!), Bleeding, Bradycardia
Prasugrel	Irreversibly blocks P2Y12	ACS undergoing PCI	Higher bleeding risk; avoid in stroke/TIA, age >75, weight <60 kg

HKMLE Pearl: Dual antiplatelet therapy (DAPT) = aspirin + P2Y12 inhibitor for 12 months post-ACS/PCI. Ticagrelor causes dyspnoea without bronchospasm (do not confuse with asthma).

10. ANTICOAGULANTS

Drug	Mechanism	Key Indication	Reversal Agent
Warfarin	Vitamin K antagonist (inhibits II, VII, IX, X, Protein C/S)	AF (stroke prevention), DVT/PE, Mechanical heart valves	Vitamin K (slow), FFP/PCC (urgent)
Heparin (UFH)	Activates antithrombin III → inactivates IIa (thrombin) + Xa	Acute DVT/PE, ACS bridging, Pregnancy (safe)	Protamine sulfate
LMWH (enoxaparin)	Activates antithrombin III → mainly anti-Xa	DVT prophylaxis/treatment, ACS, Pregnancy	Protamine (partial)
DOACs	Rivaroxaban/Apixaban = anti-Xa; Dabigatran = anti-IIa (thrombin)	AF (non-valvular), DVT/PE	Idarucizumab (dabigatran); Andexanet alfa (Xa inhibitors)

HKMLE Pearls:

Warfarin interactions: Warfarin potentiated by amiodarone, metronidazole, fluconazole. Reduced by rifampicin, carbamazepine.

Heparin-induced thrombocytopaenia (HIT): Stop heparin, switch to argatroban/lepirudin/fondaparinux. Never give platelets (paradoxically thrombogenic).

DOACs not used with mechanical heart valves (warfarin required).

11. ACUTE CORONARY SYNDROME (ACS) - Drug Management Summary

Mnemonic: "MONA BASH" (acute) + "ABCDE" (post-MI)

Acute management MONA:

M - Morphine (pain relief; note: may ↑ mortality in NSTEMI - use cautiously)
O - Oxygen (only if SpO2 <94%)
N - Nitrates (sublingual GTN - pain relief, preload reduction)
A - Aspirin 300mg loading dose

Post-MI secondary prevention ABCDE:

A - Aspirin + P2Y12 inhibitor (DAPT)
B - Beta-blocker
C - Cholesterol (statin)
D - DAPT continued + ACEI/ARB
E - Exercise/Eplerenone (if HF post-MI)

12. HEART FAILURE - Drug Summary Table

Drug Class	Mortality Benefit?	Key Indication
ACEi/ARB	YES (reduce mortality)	All HFrEF (EF <40%)
Beta-blocker (bisoprolol, carvedilol, metoprolol)	YES	HFrEF (start when stable)
Spironolactone/Eplerenone	YES	HFrEF + symptomatic despite ACEi + BB
Sacubitril/Valsartan (ARNI)	YES	Replace ACEi in HFrEF if still symptomatic
Furosemide	Symptom relief only	Fluid overload/decompensation
Digoxin	Symptom benefit only	AF + HF, refractory HFrEF
SGLT2 inhibitors (dapagliflozin)	YES (new evidence)	HFrEF and HFpEF
Ivabradine	Reduces hospitalisation	HFrEF + HR >70, sinus rhythm, on max BB dose

HKMLE Pearl: "Triple therapy" in HF = ACEi + BB + Aldosterone antagonist. Now SGLT2 inhibitors form "fantastic four." Furosemide controls symptoms but does NOT reduce mortality.

13. VASODILATORS / OTHERS

Drug	Mechanism	Key Use	Side Effect
Hydralazine	Direct arteriolar vasodilator	HF in pregnancy (safe), Hypertensive crisis in pregnancy (eclampsia)	Drug-induced lupus (like procainamide), Reflex tachycardia, Headache
Sodium nitroprusside	Releases NO → ↓ preload + afterload	Hypertensive emergency (IV only), Aortic dissection	Cyanide toxicity (thiocyanate) in prolonged use
Ivabradine	Blocks funny current (If) in SA node → ↓ HR only (no inotropy change)	HFrEF (HR >70 on max BB), Stable angina	Bradycardia, Phosphenes (visual flashes)

HKMLE Paper Distribution Summary

Topic	Most Likely Paper	MCQ Type
Antihypertensive drug selection	Paper I Medicine	Single best answer (patient scenario)
Antiarrhythmic drugs + Vaughan-Williams	Paper I Medicine	Drug identification by mechanism/side effect
Heart failure drug management	Paper I Medicine	Management sequence question
Digoxin toxicity	Paper I Medicine	Toxicity/ECG scenario
Anticoagulant reversal (HIT, warfarin overdose)	Paper I Medicine	Emergency management
Statins + rhabdomyolysis	Paper I Medicine	Drug interaction scenario
ACS management (STEMI/NSTEMI)	Paper I/Paper II	Protocol/drug sequence
Pregnancy - safe/unsafe cardiac drugs	Paper III OG	Contraindication scenario
Perioperative beta-blocker/anticoagulation	Paper II Surgery	Perioperative management

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
ACEi side effects	CAPTOPRIL = Cough, Angioedema, Potassium ↑, Teratogenic, low bP, Renal failure, Increased renin, Liver problems
Drugs causing drug-induced lupus	SHIPS = Sulfonamides, Hydralazine, Isoniazid, Procainamide, Statins (rare)
Amiodarone toxicities	THYROID LUNGS LIVER EYES SKIN (TFT, PFTs, LFTs, corneal deposits, photodermatitis)
Digoxin toxicity precipitants	DIAL = Diuretics (hypokalaemia), Impaired renal function, Amiodarone, Low Mg
Post-MI drugs	ABCDE as above
Contraindications to beta-blockers	ABCDE = Asthma, Bradycardia, Cardiogenic shock, Diabetes (relative), Elavated K (hyperK is the effect, not CI)

Sources: Lippincott Illustrated Reviews Pharmacology; Goodman & Gilman's Pharmacological Basis of Therapeutics; Braunwald's Heart Disease; Harrison's Principles of Internal Medicine 22E (2025).

Give me high-yield HKMLE notes on Respiratory Pharmacology with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - SABA/LABA - SAMA/LAMA (ipratropium, tiotropium) - Inhaled corticosteroids (ICS) - Theophylline - Montelukast (LTRA) - Mast cell stabilizers - Biologics (omalizumab, mepolizumab) - TB drugs (RIPE — Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) - Pneumonia antibiotics (CAP vs HAP) - Inhaler devices (MDI, DPI, spacer) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Cardio notes.

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All done. Here is a summary of what's covered and a few navigation tips:

What's covered:

Section	Key Exam Points
SABA/LABA	Salbutamol = reliever; LABA never alone in asthma
SAMA/LAMA	Ipratropium in acute asthma (ED adjunct); Tiotropium once-daily for COPD
ICS	Cornerstone of asthma; rinse mouth after use; budesonide safest in pregnancy
ICS + LABA combos	Symbicort MART (formoterol only) vs Seretide
Theophylline	Narrow TI; smoking lowers levels; erythromycin/ciprofloxacin raise them; seizures/arrhythmias at toxicity
Montelukast	Black box neuropsychiatric; AERD/aspirin-asthma; EGPA (rare)
Cromolyn	Prophylaxis only - no acute use
Omalizumab vs Mepolizumab	High IgE → omalizumab; high eosinophils → mepolizumab
TB RIPE	R=red urine; I=neuropathy+B6; P=gout; E=eye (optic neuritis)
CAP/HAP antibiotics	CURB-65 scoring; atypicals need macrolide/tetracycline
Inhaler devices	Child <8 → MDI+spacer; acute severe → nebuliser; DPI needs good flow

Common HKMLE traps to remember:

COPD oxygen target = 88-92% not 98%
LABA alone in asthma = wrong (black box)
Ethambutol = optic neuritis, check vision monthly
Isoniazid always needs pyridoxine (B6)
Rifampicin = major CYP inducer (OCP, warfarin, antiretrovirals all reduced)

Give me high-yield HKMLE notes on [ CNS] with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Cardio notes.

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I now have all the data I need. Let me compile the complete CNS pharmacology notes.

High-Yield HKMLE: CNS Pharmacology Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): Depression, anxiety, psychosis, epilepsy, Parkinson's, dementia, pain, substance misuse

Paper II Surgery/Emergency (45 MCQs): Acute seizures, opioid overdose, sedation

Paper III Paediatrics/OG (30 MCQs): Epilepsy in pregnancy, psychotropics in pregnancy, neonatal withdrawal

1. ANTIDEPRESSANTS

1a. SSRIs (Selective Serotonin Reuptake Inhibitors)

Mnemonic: "SSRIs = Safe, Sexual dysfunction, Serotonin syndrome risk"

Feature	Detail
Mechanism	Block serotonin (5-HT) reuptake transporter → ↑ synaptic serotonin
Key Indications	Depression (first-line), Anxiety disorders (GAD, panic, PTSD, OCD, social phobia), Bulimia (fluoxetine)
Major Side Effects	Sexual dysfunction (most common - ↓ libido, anorgasmia), Nausea/GI upset (early, resolves), Insomnia, Serotonin syndrome (if combined with MAOIs), Hyponatraemia (SIADH, especially elderly), Suicidal ideation (young adults, black box warning)
Contraindications	Concurrent MAOI use (washout 2 weeks), Bipolar depression (may trigger mania - use with mood stabiliser)
HKMLE Paper	Paper I Medicine

Key drugs: Fluoxetine (longest t½ - 1-4 days; safe in pregnancy), Sertraline, Escitalopram, Paroxetine (most sedating, most anticholinergic; avoid in pregnancy), Fluvoxamine (OCD)

HKMLE Pearls:

Fluoxetine has the longest half-life → fewest discontinuation symptoms; preferred in pregnancy

Paroxetine - most discontinuation symptoms on stopping (short t½)

All SSRIs equally effective - failure of one → try another

Takes 2-4 weeks for antidepressant effect (tell patients!)

SSRI + MAOI = serotonin syndrome (exam favourite): hyperthermia, clonus, agitation, diarrhoea, autonomic instability

1b. SNRIs (Serotonin-Noradrenaline Reuptake Inhibitors)

Feature	Detail
Mechanism	Block both 5-HT and noradrenaline reuptake
Key Indications	Depression, GAD, Neuropathic pain (duloxetine), Fibromyalgia (duloxetine), Stress urinary incontinence (duloxetine)
Major Side Effects	Similar to SSRIs + hypertension (noradrenaline effect), Sweating, Urinary hesitancy
HKMLE Paper	Paper I Medicine

Key drugs: Venlafaxine, Duloxetine

1c. TCAs (Tricyclic Antidepressants)

Mnemonic: "TCAs = Toxic in overdose, Cardiotoxic, Anticholinergic"

Feature	Detail
Mechanism	Block 5-HT + noradrenaline reuptake; also block muscarinic, histamine, α1 receptors
Key Indications	Depression (second-line), Neuropathic pain (amitriptyline), Migraine prophylaxis (amitriptyline), Enuresis in children (imipramine), Panic disorder
Major Side Effects	Anticholinergic (dry mouth, urinary retention, constipation, blurred vision), Sedation, Weight gain, QT prolongation + arrhythmias (dangerous in OD), Lethal in overdose (wide QRS, hypotension)
Contraindications	Recent MI, Arrhythmias, Narrow-angle glaucoma, Prostatic hypertrophy, Avoid after MAOI
HKMLE Paper	Paper I Medicine

Key drugs: Amitriptyline (most commonly tested), Imipramine, Clomipramine (OCD), Nortriptyline

HKMLE Pearls:

TCA overdose: wide QRS on ECG + hypotension + anticholinergic features → treatment = sodium bicarbonate IV (alkalinises, reduces Na channel block)

3 A's of TCA OD: Anticholinergic + Arrhythmia + Acidosis

1d. MAOIs (Monoamine Oxidase Inhibitors)

Mnemonic: "MAOIs = Must Avoid Old cheese (tyramine), Must Avoid Other serotonergics"

Feature	Detail
Mechanism	Inhibit MAO → ↑ serotonin, dopamine, noradrenaline in CNS
Key Indications	Refractory depression (third-line), Atypical depression (phenelzine), Social phobia
Major Side Effects	Hypertensive crisis with tyramine-rich foods (cheese, red wine, cured meats), Serotonin syndrome with SSRIs/TCAs, Postural hypotension, Weight gain
Contraindications	Concurrent SSRI/SNRI/TCA/pethidine (serotonin syndrome), Tyramine-rich diet
HKMLE Paper	Paper I Medicine

Key drugs: Phenelzine (irreversible), Tranylcypromine (irreversible), Moclobemide (reversible RIMA - safer, fewer dietary restrictions)

HKMLE Pearl: Washout period before switching: MAOI → SSRI = 2 weeks; Fluoxetine → MAOI = 5 weeks (long t½ of fluoxetine).

1e. Other Antidepressants

Drug	Mechanism	Key Feature / Side Effect
Mirtazapine	α2 antagonist + 5-HT2/5-HT3 antagonist	Weight gain + sedation (antihistaminic); NO sexual dysfunction; good for elderly/underweight depressives
Bupropion	Weak DA + NA reuptake inhibitor	Smoking cessation + depression; lowers seizure threshold (avoid in bulimia/anorexia, epilepsy); minimal sexual dysfunction
Trazodone	Weak 5-HT reuptake inhibitor + 5-HT2A antagonist	Sedating; used for insomnia; rare side effect = priapism
Vortioxetine	Multi-modal serotonergic	Fewer cognitive side effects; used in depression with cognitive symptoms

2. ANTIPSYCHOTICS

Mnemonic: "Typical = D2 block (motor side effects). Atypical = D2 + 5-HT2 block (less EPS, more metabolic)"

2a. Typical (First Generation) Antipsychotics

Feature	Detail
Mechanism	Block D2 dopamine receptors
Key Indications	Schizophrenia (acute), Mania (adjunct), Delirium, Tourette's (haloperidol)
Major Side Effects	Extrapyramidal Side Effects (EPS): Akathisia, Acute dystonia, Parkinsonism, Tardive dyskinesia (late, irreversible); Hyperprolactinaemia (galactorrhoea, amenorrhoea, sexual dysfunction); QT prolongation; Neuroleptic Malignant Syndrome (NMS)
Contraindications	Parkinson's disease (worsen motor symptoms), Prolonged QT
HKMLE Paper	Paper I Medicine, Paper II Emergency

Key drugs: Haloperidol (high potency, more EPS), Chlorpromazine (low potency, more sedation), Flupentixol (depot injection)

EPS Types and Treatment

EPS Type	Onset	Features	Treatment
Acute dystonia	Hours-days	Sudden muscle spasm (torticollis, oculogyric crisis)	IM procyclidine / benztropine
Akathisia	Days-weeks	Restlessness, inability to sit still (often mistaken for anxiety)	Reduce dose, propranolol, benzodiazepine
Parkinsonism	Weeks-months	Tremor, rigidity, bradykinesia	Anticholinergics (procyclidine)
Tardive dyskinesia	Months-years	Oro-facial movements (lip smacking, tongue protrusion)	Stop drug if possible; clonazepam; tetrabenazine

2b. Neuroleptic Malignant Syndrome (NMS) - High Yield!

Mnemonic: "FALTER" = Fever, Altered consciousness, Lead-pipe rigidity, Tachycardia/instability, Elevated CK, Rhabdomyolysis

Feature	Detail
Cause	Any antipsychotic (typical > atypical); also sudden withdrawal of dopaminergic drugs
Features	Hyperthermia, Severe rigidity (lead-pipe), Altered consciousness, Autonomic instability, ↑ CK (rhabdomyolysis), ↑ WBC
Treatment	Stop antipsychotic immediately; supportive (cooling, hydration); Dantrolene (muscle relaxant); Bromocriptine (dopamine agonist)
Distinguish from	Serotonin syndrome (clonus/hyperreflexia, not rigidity; diarrhoea)

2c. Atypical (Second Generation) Antipsychotics

Drug	Key Features	Unique Side Effects
Clozapine	Treatment-resistant schizophrenia only	Agranulocytosis (monitor FBC weekly x 18 weeks, then monthly); Seizures; Hypersalivation; Weight gain; Myocarditis; No EPS
Olanzapine	Schizophrenia, Bipolar mania, Acute agitation (IM)	Metabolic syndrome (weight gain, diabetes, dyslipidaemia); Sedation
Risperidone	Schizophrenia, Bipolar, Behaviour in autism	Hyperprolactinaemia (most of atypicals); EPS at high doses
Quetiapine	Schizophrenia, Bipolar depression, Augmentation in depression	Sedation; Postural hypotension; Metabolic effects; Least EPS
Aripiprazole	Schizophrenia, Bipolar, Augmentation	Partial D2 agonist (unique mechanism); Akathisia; Least metabolic effects
Amisulpride	Schizophrenia (especially negative symptoms)	Hyperprolactinaemia; QT prolongation

HKMLE Pearls:

Clozapine = only drug for treatment-resistant schizophrenia (failed 2 antipsychotics). Agranulocytosis = MUST monitor FBC.

Metabolic syndrome = atypical antipsychotics → monitor weight, glucose, lipids

Quetiapine = most used for bipolar depression among atypicals

Aripiprazole = partial D2 agonist (not a pure antagonist - exam trap)

3. ANXIOLYTICS / HYPNOTICS

3a. Benzodiazepines

Mnemonic: "BZDs = Bind GABA, Big sedation, Beware dependence"

Feature	Detail
Mechanism	Positive allosteric modulator at GABA-A receptor (Cl- channel) → ↑ frequency of Cl- channel opening → CNS depression
Key Indications	Acute anxiety/panic attacks, Alcohol withdrawal (first-line), Acute seizures (IV lorazepam/diazepam), Procedural sedation, Muscle spasm, Insomnia (short-term only)
Major Side Effects	Sedation, Cognitive impairment, Anterograde amnesia, Respiratory depression (overdose), Dependence and withdrawal (seizures, delirium on abrupt stop), Falls/hip fracture in elderly
Contraindications	Sleep apnoea, Severe respiratory depression, Pregnancy (cleft palate risk), Myasthenia gravis
Reversal agent	Flumazenil (competitive antagonist; short-acting - re-sedation can occur)
HKMLE Paper	Paper I Medicine, Paper II Emergency, Paper III

Drug	Duration	Key Use
Diazepam	Long (active metabolites days)	Alcohol withdrawal, Seizures, Anxiety, Muscle spasm
Lorazepam	Intermediate	Acute seizure (IV), Pre-op sedation, Status epilepticus
Midazolam	Short	Procedural sedation, ICU sedation
Clonazepam	Long	Epilepsy, Panic disorder
Temazepam	Short	Insomnia

HKMLE Pearls:

Status epilepticus first-line = IV/rectal/buccal lorazepam/diazepam

Alcohol withdrawal = diazepam (long-acting → prevents seizures/DTs)

Flumazenil reverses BZD sedation but NOT respiratory depression from other drugs; short-acting → re-sedation risk

BZD + opioid = ↑ respiratory depression risk (black box)

3b. Z-Drugs (Non-BZD Hypnotics)

Feature	Detail
Mechanism	Same GABA-A site as BZDs (benzodiazepine binding site) but more selective for α1 subunit → more hypnotic, less anxiolytic/anticonvulsant
Key Indications	Short-term insomnia only
Major Side Effects	Dependence (similar to BZDs), Rebound insomnia, Sleepwalking/complex sleep behaviours, Amnesia
HKMLE Paper	Paper I Medicine

Key drugs: Zolpidem, Zopiclone, Zaleplon

HKMLE Pearl: Z-drugs are NOT significantly safer than BZDs for dependence. NICE recommends short-term use only (2-4 weeks max).

3c. Buspirone

Feature	Detail
Mechanism	5-HT1A partial agonist; also weak D2 antagonist
Key Indications	Generalised Anxiety Disorder (GAD) - long-term (not acute anxiety)
Major Side Effects	Dizziness, Headache, Nausea - no dependence, no sedation, no cognitive impairment
HKMLE Tip	Delayed onset (2-4 weeks); no cross-tolerance with BZDs (cannot replace BZD acutely)

4. ANTIEPILEPTIC DRUGS (AEDs)

Mnemonic for mechanisms: "Sodium Blocks Fits, Calcium Crushes Absence, GABA Guards neurons"

Drug-by-Drug HKMLE Table

Drug	Mechanism	Seizure Type	Key Side Effects	HKMLE-Specific Points
Sodium Valproate	↑ GABA, ↓ Na+ channels, ↓ T-type Ca2+	Broad spectrum (all types) incl. absence	Hepatotoxicity, Pancreatitis, Weight gain, Tremor, Alopecia, Neural tube defects (teratogen!), Thrombocytopenia, PCOS	Avoid in women of childbearing age - highest teratogen risk of all AEDs
Carbamazepine	Blocks voltage-gated Na+ channels	Focal, Generalised tonic-clonic, Trigeminal neuralgia	Hyponatraemia (SIADH), Aplastic anaemia, Stevens-Johnson syndrome, Diplopia, Ataxia, Teratogen (neural tube defects), CYP inducer (↓ OCP, warfarin)	Associated with *HLA-B1502 (Asians) → SJS risk; check before prescribing; contraindicated in absence/myoclonic seizures**
Phenytoin	Blocks Na+ channels (phase 4)	Focal, Generalised tonic-clonic, Status epilepticus (IV)	Zero-order kinetics (small dose → large change in levels!), Gingival hyperplasia, Hirsutism, Coarse facies, Megaloblastic anaemia, Ataxia, Nystagmus (toxicity), Teratogen, CYP inducer	Zero-order (saturation) kinetics = most tested phenytoin fact; narrow therapeutic index (10-20 µg/mL)
Lamotrigine	Blocks Na+ channels	Focal, Generalised (incl. absence), Bipolar disorder	Stevens-Johnson syndrome (especially with rapid titration or with valproate), Rash, Headache, Diplopia	Safest AED in pregnancy (with folate); titrate slowly to avoid SJS
Levetiracetam	Binds SV2A synaptic vesicle protein	Broad spectrum (focal, generalised, myoclonic)	Irritability, Behavioural changes/depression (psychiatric side effects), Headache	Increasingly used as first-line; renally cleared; minimal drug interactions
Ethosuximide	Blocks T-type Ca2+ channels	Absence seizures ONLY	Nausea, Headache, Drowsiness	Drug of choice for pure absence (petit mal) - does NOT work for other seizure types
Phenobarbitone	↑ GABA-A Cl- channel duration of opening	Generalised tonic-clonic, Status epilepticus	Sedation, Dependence, Cognitive impairment, CYP inducer, Teratogen	Neonatal seizures (IV); sedating - not ideal long-term
Gabapentin / Pregabalin	Bind α2δ subunit of voltage-gated Ca2+ channels	Focal seizures (adjunct); Neuropathic pain, Fibromyalgia	Sedation, Dizziness, Weight gain, Peripheral oedema	Pregabalin also for GAD; abuse potential (schedule 3 in UK)
Topiramate	Na+ block + GABA ↑ + AMPA antagonism	Focal, Generalised, Migraine prophylaxis	Weight loss (useful side effect!), Cognitive dulling ("Dope-amax"), Kidney stones (carbonic anhydrase inhibition), Teratogen (cleft lip)	Unique: causes weight LOSS unlike most AEDs

Seizure Type → First-Line Drug

Seizure Type	First Choice	Avoid
Focal (partial)	Carbamazepine, Lamotrigine, Levetiracetam	Valproate in women
Generalised tonic-clonic	Valproate, Lamotrigine, Levetiracetam	Carbamazepine may worsen absence/myoclonic
Absence (petit mal)	Ethosuximide (pure absence), Valproate	Carbamazepine, Phenytoin (can worsen!)
Myoclonic	Valproate, Levetiracetam, Clonazepam	Carbamazepine, Phenytoin
Status epilepticus	Lorazepam IV → Phenytoin/Levetiracetam → Phenobarbitone	-

AEDs in Pregnancy - HKMLE Exam Trap

Drug	Risk	Action
Valproate	Highest risk (neural tube defects, spina bifida, neurodevelopmental delay)	AVOID in women of childbearing age unless no alternative
Carbamazepine	Neural tube defects	Prescribe with folic acid 5mg/day
Phenytoin	Fetal hydantoin syndrome (cleft palate, digit defects)	Avoid if possible
Lamotrigine	Lowest risk among older AEDs	Preferred; levels drop in pregnancy (dose increase needed)
Levetiracetam	Low risk (limited data)	Increasingly used

HKMLE Pearl: All women of childbearing age on AEDs → folic acid 5mg/day (not 400mcg - higher dose needed). Valproate → avoid or document risks + contraception.

5. PARKINSON'S DISEASE DRUGS

Mnemonic: "LMAD" = Levodopa, MAO-B inhibitors, Agonists (DA), DOPA decarboxylase inhibitor (carbidopa)"

Drug Summary Table

Drug	Mechanism	Key Use	Side Effects	HKMLE Tips
Levodopa + Carbidopa (Co-careldopa, Sinemet)	L-DOPA → dopamine in CNS; carbidopa blocks peripheral decarboxylase → ↓ peripheral SE	Most effective Parkinson drug (gold standard)	On-off fluctuations (wearing off), Dyskinesias (at high doses), Nausea, Psychosis/hallucinations, Postural hypotension	Carbidopa reduces nausea + allows lower levodopa dose; on-off = disease progression
Dopamine Agonists (Pramipexole, Ropinirole, Rotigotine)	Directly stimulate D2/D3 receptors	Early PD (younger patients, delay levodopa), Adjunct to levodopa, Restless Legs Syndrome	Nausea, Postural hypotension, Somnolence, Impulse control disorders (gambling, hypersexuality), Hallucinations	Impulse control disorders = exam favourite; Rotigotine = transdermal patch
MAO-B Inhibitors (Selegiline, Rasagiline)	Block MAO-B → ↓ dopamine breakdown in CNS	Early PD (monotherapy or adjunct)	Insomnia (selegiline → amphetamine metabolites), Drug interactions (serotonin syndrome with pethidine/SSRIs)	Avoid pethidine (meperidine) - serotonin syndrome
COMT Inhibitors (Entacapone, Tolcapone)	Block catechol-O-methyltransferase → ↓ peripheral levodopa breakdown → more L-DOPA enters brain	Adjunct for wearing-off with levodopa	Diarrhoea, Dyskinesias, Orange urine; Tolcapone: hepatotoxicity (monitor LFTs)	Given WITH every dose of levodopa
Anticholinergics (Procyclidine, Benztropine, Trihexyphenidyl)	Block muscarinic receptors → restore DA/ACh balance	Tremor-predominant PD (especially in younger patients), Drug-induced parkinsonism	Dry mouth, Urinary retention, Constipation, Confusion (avoid in elderly)	Avoid in elderly (confusion, falls); useful for drug-induced parkinsonism and acute dystonia
Amantadine	Releases DA, NMDA antagonist	Mild PD; reducing dyskinesias in late PD	Livedo reticularis, Ankle oedema, Confusion, Hallucinations	Useful for dyskinesias (unique indication)

HKMLE Pearls:

Never give antipsychotics (D2 blockers) to Parkinson's patients - worsens motor symptoms; exception = quetiapine or clozapine (least D2 block) if psychosis unavoidable

Pethidine (meperidine) + MAO-B inhibitors = serotonin syndrome (exam favourite)

Levodopa + carbidopa: carbidopa does NOT cross BBB → only reduces peripheral side effects

On-off phenomenon = motor fluctuations with levodopa in advanced PD

6. DEMENTIA DRUGS (Alzheimer's Disease)

Mnemonic: "4 drugs: 3 AChE inhibitors + 1 NMDA antagonist (Memantine)"

Drug	Mechanism	Indication	Side Effects	HKMLE Tips
Donepezil	Reversible AChE inhibitor	Mild-moderate-severe AD	GI (nausea, diarrhoea), Bradycardia, Nightmares	Once daily; only AChEI approved for severe AD
Rivastigmine	AChE + BuChE inhibitor	Mild-moderate AD; Parkinson's disease dementia	GI side effects; available as transdermal patch	Only drug approved for PD dementia
Galantamine	AChE inhibitor + nicotinic receptor modulator	Mild-moderate AD	GI side effects	Modest additional nicotinic effect
Memantine	NMDA receptor antagonist (non-competitive)	Moderate-severe AD	Dizziness, Headache, Constipation; well tolerated	Can be combined with AChEI in moderate-severe AD; addresses excitotoxicity

HKMLE Pearls:

None of these drugs cure or stop progression - symptomatic only

Bradycardia with donepezil - monitor if patient has SSS/heart block

Lewy body dementia: AChEIs useful; antipsychotics SEVERELY contraindicated (severe Parkinsonism/death)

Vascular dementia: manage risk factors (antihypertensives, statins, aspirin); AChEIs less evidence

7. OPIOID ANALGESICS

Mnemonic: "OPIOIDS = Oppressive Pupils, Itching, Overdose-respiratory depression, Ileus, Dependence, Sedation"

Feature	Detail
Mechanism	Agonists at μ (mu), κ (kappa), δ (delta) opioid receptors → ↓ pain transmission, ↓ cough reflex, ↓ GI motility
Key Indications	Moderate-severe acute pain, Cancer pain (WHO pain ladder), Palliative care, Cough suppression (codeine), Acute pulmonary oedema (morphine)
Major Side Effects	Respiratory depression (most dangerous), Constipation (never develops tolerance - always treat!), Nausea/vomiting, Sedation, Urinary retention, Miosis (pinpoint pupils), Pruritus, Dependence
Contraindications	Head injury with ↑ ICP (mask changes, CO2 retention worsens), Concurrent MAOI (pethidine specifically), Severe respiratory depression
HKMLE Paper	Paper I Medicine, Paper II Emergency

Opioid Drug Comparison

Drug	Notes
Morphine	Standard; active metabolite (morphine-6-glucuronide) accumulates in renal failure → toxicity; oral/IV/SC
Codeine	Prodrug → converted to morphine by CYP2D6 (poor metabolisers: no effect; ultra-rapid metabolisers: toxicity); avoid in children post-tonsillectomy
Tramadol	Weak μ agonist + SNRI (dual mechanism); lowers seizure threshold; serotonin syndrome risk with SSRIs; not a true opioid but treated as one
Fentanyl	High potency (100x morphine); transdermal patch for chronic pain; buccal for breakthrough pain
Pethidine (Meperidine)	Toxic metabolite (norpethidine) → seizures; avoid in renal failure; serotonin syndrome with MAOIs; avoid in Parkinson's patients on selegiline
Buprenorphine	Partial μ agonist; ceiling effect on respiratory depression; opioid dependence treatment (sublingual ± naloxone = Suboxone)
Methadone	Full μ agonist; long t½ (unpredictable); opioid substitution therapy; QT prolongation

Opioid Overdose

Feature	Detail
Triad	Coma + Respiratory depression + Miosis (pinpoint pupils)
Treatment	IV/IM/intranasal Naloxone (competitive μ antagonist)
Naloxone caution	Short-acting (t½ ~60-90 min) - repeat doses or infusion needed for long-acting opioids

8. MIGRAINE DRUGS

Drug	Mechanism	Use	Side Effects
Triptans (Sumatriptan)	5-HT1B/1D agonist → vasoconstriction of meningeal vessels, ↓ neuropeptide release	Acute migraine attack (first-line)	Chest tightness, Paresthesia, Flushing; Contraindicated in IHD, uncontrolled HTN, hemiplegic migraine
Aspirin/NSAIDs	Prostaglandin inhibition	Mild-moderate migraine (with/without antiemetic)	GI side effects
Ergotamine	5-HT1B/1D + α agonist (vasoconstriction)	Acute migraine (now less used)	Ergotism (peripheral vasospasm, gangrene), nausea; contraindicated in vascular disease
Propranolol	β-blocker	Migraine prophylaxis (first-line)	Bradycardia, bronchospasm; avoid in asthma
Amitriptyline	TCA	Migraine prophylaxis	Sedation, weight gain, anticholinergic
Topiramate	Multi-mechanism AED	Migraine prophylaxis	Cognitive dulling, weight loss, kidney stones
CGRP antagonists (Erenumab, Fremanezumab)	Monoclonal Ab vs CGRP/receptor	Refractory migraine prophylaxis	Injection site reactions, constipation

9. SUBSTANCE MISUSE / DEPENDENCE DRUGS

Drug	Use	Mechanism/Notes
Methadone	Opioid substitution therapy	Long t½ μ agonist; daily supervised dispensing; reduces illicit opioid use
Buprenorphine ± Naloxone (Suboxone)	Opioid substitution	Partial agonist + ceiling on respiratory depression; harder to misuse (naloxone deters IV injection)
Naltrexone	Alcohol dependence, Opioid relapse prevention	Opioid receptor antagonist; reduces craving for alcohol (mechanism unclear); oral or monthly injection
Acamprosate	Alcohol dependence (abstinence maintenance)	GABA agonist/NMDA antagonist → reduces craving; start after detox
Disulfiram	Alcohol deterrent	Blocks ALDH → acetaldehyde accumulates → flushing, nausea, headache, hypotension if alcohol consumed; requires motivated patient
Nicotine replacement	Smoking cessation	Reduces withdrawal symptoms; patch, gum, lozenge
Varenicline (Champix)	Smoking cessation	Partial α4β2 nicotinic ACh receptor agonist; most effective single agent; neuropsychiatric warning (depression, suicidal ideation)
Bupropion	Smoking cessation	DA/NA reuptake inhibitor; also used in depression

HKMLE Pearl: Disulfiram reaction = acetaldehyde syndrome. Metronidazole + alcohol causes the same reaction (also inhibits ALDH).

SEROTONIN SYNDROME vs NMS - Exam Comparison

Feature	Serotonin Syndrome	Neuroleptic Malignant Syndrome
Cause	Excess serotonin (SSRI + MAOI, SSRI + tramadol, SSRI + linezolid)	Dopamine blockade (antipsychotics) or DA drug withdrawal
Onset	Rapid (hours)	Slower (days)
Tone	Clonus, hyperreflexia, myoclonus	Lead-pipe rigidity
Pupils	Dilated (mydriasis)	Normal or small
Temp	Hyperthermia	High fever
GI	Diarrhoea	-
CK	Normal or mildly ↑	Markedly elevated
Treatment	Cyproheptadine (5-HT antagonist); supportive; BZDs	Stop antipsychotic; Dantrolene, Bromocriptine

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
SSRI side effects / serotonin syndrome	Paper I Medicine	Drug interaction / toxicity scenario
TCA overdose management (sodium bicarb)	Paper I / Paper II	Emergency management
Antipsychotic EPS types and treatment	Paper I Medicine	Side effect identification
Clozapine agranulocytosis monitoring	Paper I Medicine	Monitoring protocol
NMS vs Serotonin Syndrome	Paper I Medicine	Differentiating diagnosis
AED selection by seizure type	Paper I Medicine	Drug selection MCQ
AEDs in pregnancy (valproate teratogenicity)	Paper I / Paper III	Contraindication scenario
Phenytoin zero-order kinetics	Paper I Medicine	Pharmacokinetics
Levodopa on-off / dyskinesia	Paper I Medicine	Long-term complication
Opioid overdose (naloxone)	Paper II Emergency	Overdose management
Dementia drugs (AChEI in PD dementia)	Paper I Medicine	Drug selection
Migraine prophylaxis vs acute	Paper I Medicine	Drug choice scenario
Alcohol dependence drugs	Paper I Medicine	Drug mechanism/indication

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
SSRI side effects	SSRI = Sexual dysfunction, Serotonin syndrome risk, SIADH (Na↓), Initial anxiety/activation
TCA overdose	3 C's = Convulsions, Coma, Cardiac arrhythmia → treat with NaHCO3
Antipsychotic EPS timeline	"Acutely Agitated Patients Take Drugs" = Acute Dystonia → Akathisia → Parkinsonism → Tardive Dyskinesia
NMS features	FALTER = Fever, Altered consciousness, Lead-pipe rigidity, Tachycardia/autonomic instability, Elevated CK, Rhabdomyolysis
AED seizure matching	Absence = Ethosuximide, Myoclonic = Valproate, Focal = Carbamazepine
Valproate toxicity	HALT = Hepatotoxicity, Alopecia, Liver failure, Teratogen (neural tube)
Phenytoin side effects	GANG = Gingival hyperplasia, Ataxia/nystagmus, Nystagmus (toxicity), Gum problems (zero-order kinetics trap)
Opioid overdose triad	RMP = Respiratory depression, Miosis (pinpoint pupils), coma
Parkinson drugs	LMAD = Levodopa/carbidopa, MAO-B inhibitors, Agonists (DA), DOPA decarboxylase inhibitor

Sources: Lippincott Illustrated Reviews Pharmacology; Goodman & Gilman's Pharmacological Basis of Therapeutics; Kaplan & Sadock's Comprehensive Textbook of Psychiatry; The Maudsley Prescribing Guidelines in Psychiatry 15th Edition; Adams & Victor's Principles of Neurology 12th Edition; Harrison's Principles of Internal Medicine 22E (2025).

Give me high-yield HKMLE notes on Endocrine Pharmacology with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - Diabetes drugs (insulin types, metformin, sulfonylureas, SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, TZDs) - Thyroid drugs (methimazole, propylthiouracil, levothyroxine) - Corticosteroids (prednisolone, dexamethasone, hydrocortisone) - Bone/metabolism drugs (bisphosphonates, denosumab, PTH analogs, calcitonin) - Pituitary drugs (desmopressin, vasopressin, somatostatin analogs) - Adrenal insufficiency management Use tables where helpful. No long paragraphs. No fluff. Match the style of my Cardio notes.

Reading File

Finding Sources

Reading File

Finding Sources

I now have comprehensive data from Lippincott and other textbooks. Let me compile the full HKMLE endocrine pharmacology notes.

High-Yield HKMLE: Endocrine Pharmacology Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): Diabetes, thyroid, adrenal, osteoporosis, pituitary

Paper II Surgery/Emergency (45 MCQs): DKA management, thyroid storm, adrenal crisis, perioperative steroids

Paper III Paediatrics/OG (30 MCQs): Gestational diabetes, thyroid drugs in pregnancy, GDM insulin use

1. INSULIN

Mnemonic: "RAP = Rapid, Aspart/Lispro, Prandial" | "NGL = NPH Goes Long" | "Glargine = Gliding basal (no peak)"

Insulin Type Reference Table

Type	Onset	Peak	Duration	Key Use	Examples
Rapid-acting	15-30 min	30-90 min	3-5h	Mealtime (prandial) - give 15 min before meal	Lispro, Aspart, Glulisine
Short-acting	30 min	1-3h	6-8h	Mealtime; IV infusion (DKA); give 30 min before meal	Regular (Actrapid)
Intermediate-acting	1-2h	4-12h	12-18h	Basal (BD dosing); not IV	NPH (Insulatard)
Long-acting	1-2h	No peak	20-24h	Once-daily basal	Glargine (Lantus), Detemir, Degludec

HKMLE Pearls:

Only Regular (soluble) insulin and rapid-acting analogs can be given IV (e.g., DKA protocols)

NPH = NEVER give IV - always subcutaneous

Glargine has no peak → least hypoglycaemia risk at night

IV insulin infusion = short-acting (regular) only

Insulin Side Effects

Side Effect	Detail
Hypoglycaemia	Most common and dangerous; treat with 15-20g fast carbs orally or IV dextrose/IM glucagon
Lipodystrophy	Lipoatrophy or lipohypertrophy at injection sites (rotate sites!)
Weight gain	All insulins cause weight gain
Hypokalaemia	Insulin drives K+ into cells; critical in DKA management

2. METFORMIN (Biguanide)

Mnemonic: "Metformin = Must exclude renal failure, Metabo-protective, Minimal hypoglycaemia"

Feature	Detail
Mechanism	Activates AMPK → ↓ hepatic gluconeogenesis (primary), ↑ peripheral insulin sensitivity, ↓ GI glucose absorption
Key Indications	First-line for T2DM (all guidelines), Polycystic ovary syndrome (PCOS), Prediabetes prevention
Major Side Effects	GI (nausea, diarrhoea, metallic taste - most common; take with food), Lactic acidosis (rare but serious), Vitamin B12 deficiency (long-term)
Contraindications	eGFR <30 (lactic acidosis risk); Withold when IV contrast/surgery/severe illness/acute HF; Hepatic failure; Alcoholism
HKMLE Paper	Paper I Medicine, Paper III OG

HKMLE Pearls:

No hypoglycaemia as monotherapy (does not stimulate insulin release)

Hold metformin 48h before IV contrast (iodinated contrast → ↓ renal clearance → lactic acidosis)

Metformin is weight-neutral or causes slight weight loss - preferred in obese T2DM

Safe in mild CKD (eGFR 30-60 = caution/reduce dose; eGFR <30 = stop)

3. SULFONYLUREAS

Mnemonic: "SULFONYLureas = SULK if no glucose = Stimulate insulin regardless of sugar level"

Feature	Detail
Mechanism	Close ATP-sensitive K+ channels on pancreatic β-cells → depolarisation → Ca2+ influx → insulin secretion (glucose-independent)
Key Indications	T2DM (2nd line after metformin or add-on), Elderly patients with reasonable renal function
Major Side Effects	Hypoglycaemia (most significant - prolonged, especially glibenclamide), Weight gain, Hyponatraemia (SIADH - chlorpropamide), Disulfiram-like reaction with alcohol (chlorpropamide)
Contraindications	Severe renal impairment (hypoglycaemia risk; prefer gliclazide which is hepatically metabolised), Pregnancy, T1DM
HKMLE Paper	Paper I Medicine

Drug	Duration	Renal Safety	Notes
Glibenclamide (Glyburide)	Long	Avoid in renal impairment	Highest hypoglycaemia risk; active metabolites accumulate
Gliclazide	Moderate	Safer in CKD	Hepatically metabolised; preferred in renal impairment
Glipizide	Short	Moderate	Shorter-acting; less hypoglycaemia
Glimepiride	Once daily	Moderate

HKMLE Pearl: Elderly patient + sulfonylurea + prolonged hypoglycaemia = gliclazide or glipizide (shorter-acting safer). Glibenclamide is the most dangerous in the elderly.

4. SGLT2 INHIBITORS (Gliflozins)

Mnemonic: "SGLT2 = Sugar Goes via urine (Loss To peE) = UTI, DKA, HF benefit"

Feature	Detail
Mechanism	Inhibit SGLT2 cotransporter in proximal tubule → block renal glucose reabsorption → glycosuria → lower BGL; also causes natriuresis and osmotic diuresis
Key Indications	T2DM + established CVD (↓ CV mortality - EMPA-REG), T2DM + HFrEF (↓ hospitalisation), T2DM + CKD (↓ progression), HFrEF without diabetes (dapagliflozin, empagliflozin)
Major Side Effects	Genital mycotic infections (UTI, vulvovaginal candidiasis - most common), Euglycaemic DKA (BGL may be near-normal!), Fournier's gangrene (necrotising fasciitis of perineum), Polyuria, Dehydration/hypotension, Bone fractures (canagliflozin)
Contraindications	eGFR <30 (reduced efficacy + safety concern; dapagliflozin contraindicated <25), T1DM (euglycaemic DKA risk), Recurrent UTIs
HKMLE Paper	Paper I Medicine

Drug	Additional Indication
Empagliflozin	Reduces CV death (EMPA-REG OUTCOME); HFrEF
Dapagliflozin	HFrEF (with/without DM); CKD
Canagliflozin	CV + renal protection

HKMLE Pearls:

Euglycaemic DKA = ketosis + normal/near-normal glucose → easy to miss! Hold SGLT2i 3 days before surgery

Weight loss + BP reduction = bonus effects (not primary indication for HTN)

No hypoglycaemia as monotherapy

5. GLP-1 RECEPTOR AGONISTS

Mnemonic: "GLP-1 = Gut slows, Less appetite, Pumps insulin when glucose HIGH, 1 injection weekly/daily"

Feature	Detail
Mechanism	Mimic incretin hormone GLP-1 → glucose-dependent insulin secretion, ↓ glucagon, ↓ gastric emptying (→ satiety), acts on hypothalamus to ↓ appetite
Key Indications	T2DM (add-on, especially obese patients); Obesity (semaglutide 2.4mg/week = Wegovy); CV risk reduction (liraglutide, semaglutide in T2DM + CVD)
Major Side Effects	Nausea/vomiting (most common, dose-dependent, improves with time), Diarrhoea, Pancreatitis (rare but important), Injection site reactions
Contraindications	Medullary thyroid carcinoma (MTC) history or family history (black box warning - rodent studies showed C-cell tumours), MEN type 2, Pancreatitis history
HKMLE Paper	Paper I Medicine

Drug	Route	Frequency	Special Note
Liraglutide	SC	Once daily	CV benefit (LEADER trial); also approved for obesity (3mg)
Semaglutide	SC / Oral	Once weekly / once daily	Most potent weight loss; oral form available; also for obesity
Dulaglutide	SC	Once weekly	CV benefit (REWIND trial)
Exenatide	SC	BD or once weekly	First approved GLP-1 agonist

HKMLE Pearls:

No hypoglycaemia as monotherapy (glucose-dependent mechanism)

Weight loss = significant (5-15% body weight with semaglutide)

C-cell tumour warning = contraindicated in MEN2 and MTC

6. DPP-4 INHIBITORS (Gliptins)

Mnemonic: "Gliptins = Gentle, no hypo, no weight, nasty joints (arthralgia)"

Feature	Detail
Mechanism	Inhibit DPP-4 enzyme → prevent degradation of endogenous GLP-1 and GIP → ↑ glucose-dependent insulin secretion, ↓ glucagon
Key Indications	T2DM (add-on to metformin); well tolerated in elderly and renal impairment (dose-adjust)
Major Side Effects	Generally well tolerated; Nasopharyngitis/URTI (most common), Arthralgia (joint pain - black box warning), Rare: pancreatitis, Heart failure risk with saxagliptin
Contraindications	History of pancreatitis (relative), Heart failure (avoid saxagliptin specifically)
HKMLE Paper	Paper I Medicine

Key drugs: Sitagliptin, Vildagliptin, Saxagliptin, Alogliptin, Linagliptin (hepatically eliminated - safe in renal failure)

HKMLE Pearl: Weight neutral, no hypoglycaemia - preferred in elderly or when weight/hypoglycaemia are concerns. Linagliptin = only gliptin that does NOT need renal dose adjustment.

7. THIAZOLIDINEDIONES (TZDs / Glitazones)

Mnemonic: "TZDs = Thick fluid (oedema), Zero bone (fractures), Dangerous heart (HF)"

Feature	Detail
Mechanism	Activate PPAR-γ nuclear receptor → ↑ insulin sensitivity in muscle, liver, adipose tissue (insulin sensitiser)
Key Indications	T2DM (add-on); NAFLD/NASH (pioglitazone); T2DM with insulin resistance
Major Side Effects	Fluid retention/peripheral oedema, Heart failure exacerbation, Weight gain, Bone fractures (↑ in women), Bladder cancer risk (pioglitazone - long-term)
Contraindications	Heart failure (any class), Bladder cancer, Hepatic impairment, Osteoporosis
HKMLE Paper	Paper I Medicine

Key drugs: Pioglitazone (only one available after rosiglitazone withdrawn due to CV risk)

HKMLE Pearl: HF is a hard contraindication. Rosiglitazone was withdrawn due to ↑ MI risk. Pioglitazone may reduce CV events but causes bladder cancer risk with long-term use.

8. DIABETES DRUG QUICK-SELECT TABLE

Clinical Scenario	Preferred Drug(s)
T2DM first-line	Metformin
T2DM + HFrEF	SGLT2i (dapagliflozin, empagliflozin)
T2DM + established CVD	SGLT2i or GLP-1 agonist (empagliflozin, liraglutide, semaglutide)
T2DM + CKD	SGLT2i (dapagliflozin); avoid metformin if eGFR <30
T2DM + obesity	GLP-1 agonist (semaglutide, liraglutide)
T2DM + elderly	Gliptin or gliclazide (avoid hypoglycaemia)
T2DM + pregnancy (GDM)	Metformin (or insulin); sulfonylureas debated
T1DM	Insulin only

9. THYROID DRUGS

9a. Antithyroid Drugs

Mnemonic: "PTU = Preferred in Trimester 1 & crisis (Unblocks T4→T3 conversion); Carbimazole/Methimazole = use after 1st trimester"

Feature	Carbimazole / Methimazole	Propylthiouracil (PTU)
Mechanism	Block thyroid peroxidase → ↓ iodination of tyrosine residues → ↓ T3/T4 synthesis	Same PLUS blocks peripheral T4 → T3 conversion
Key Indications	Hyperthyroidism (Graves', toxic nodule)	Thyroid storm (preferred), 1st trimester pregnancy (carbimazole causes aplasia cutis)
Major Side Effects	Agranulocytosis (0.5%; both drugs - tell patient to report sore throat!), Rash, Liver toxicity (PTU > carbimazole)	Agranulocytosis, Hepatotoxicity (PTU has higher risk), Vasculitis
Onset of action	6-8 weeks for euthyroid state	Same
HKMLE Paper	Paper I Medicine, Paper III OG

HKMLE Pearls:

Agranulocytosis with antithyroids = sore throat/fever → stop drug, check FBC immediately

1st trimester: use PTU (carbimazole associated with aplasia cutis, choanal atresia)

2nd/3rd trimester + postpartum: switch to carbimazole/methimazole (PTU hepatotoxic)

Thyroid storm: PTU + propranolol + iodine (Lugol's) + hydrocortisone + cooling

Thyroid Storm Management (HKMLE Exam)

Mnemonic: "BIIP" = Block synthesis (PTU) + Iodine (Lugol's - given AFTER PTU) + Iodide uptake block (β-blocker) + Prednisolone

Drug	Role
PTU (high dose)	Block hormone synthesis + T4→T3 conversion
Lugol's iodine	Block hormone release (Wolff-Chaikoff; given AFTER PTU, NOT before)
Propranolol (IV)	Control tachycardia, block T4→T3 conversion (peripheral)
Hydrocortisone IV	↓ T4→T3 conversion; treats relative adrenal insufficiency
Cooling / Paracetamol	Treat hyperpyrexia (avoid aspirin - displaces T4 from binding)

9b. Levothyroxine (T4)

Mnemonic: "Levothyroxine = Long half-life (7 days), one morning dose (empty stomach), Less interaction with food"

Feature	Detail
Mechanism	Synthetic T4 → converted to active T3 in peripheral tissues
Key Indications	Hypothyroidism (primary, secondary), Post-thyroidectomy replacement, Myxoedema coma (IV T3 or T4)
Major Side Effects	Signs of hyperthyroidism if overdosed: Palpitations, tremor, weight loss, AF, osteoporosis (long-term), Angina worsening
Contraindications	Untreated adrenal insufficiency (precipitates adrenal crisis - must give steroids first!), Acute MI (relative)
HKMLE Paper	Paper I Medicine, Paper III OG

HKMLE Pearls:

Take on empty stomach 30-60 min before breakfast (food ↓ absorption)

Start LOW in elderly/IHD patients (↑ O2 demand can precipitate angina)

Myxoedema coma: IV T3 (liothyronine) or T4 + IV hydrocortisone + rewarming + ICU

TSH monitoring: takes 6 weeks after dose change (slow T4 t½)

Pregnancy: increase dose by ~25-50% in hypothyroid women (↑ TBG demand)

10. CORTICOSTEROIDS

Mnemonic: "STEROIDS = Sugar up (hyperglycaemia), Thin skin/bones, Edema, Raised BP, Obesity (cushingoid), Infections↑, Delayed wound healing, Suppression of HPA axis"

Steroid Comparison Table

Drug	Glucocorticoid Potency	Mineralocorticoid Potency	Duration	Key Use
Hydrocortisone	1 (reference)	1	Short (8-12h)	Acute adrenal crisis (IV), physiological replacement, anaphylaxis
Prednisolone	4	0.8	Intermediate (12-36h)	Most oral anti-inflammatory/immunosuppressive use
Methylprednisolone	5	0.5	Intermediate	IV pulse therapy (MS relapse, lupus nephritis, transplant rejection)
Dexamethasone	25-30	0 (no mineralocorticoid)	Long (36-54h)	Cerebral oedema, Croup, Fetal lung maturation (antenatal), Dexamethasone suppression test, Anti-emetic (chemotherapy), COVID-19 severe
Fludrocortisone	10	250 (high)	-	Adrenal insufficiency mineralocorticoid replacement, Conn syndrome management

Corticosteroid Side Effects (All Exam-Tested)

System	Side Effects
Metabolic	Hyperglycaemia, Dyslipidaemia, Weight gain, Cushingoid features (moon face, buffalo hump, striae)
Bone	Osteoporosis (↓ bone formation + ↑ resorption), Avascular necrosis (femoral head)
Adrenal	HPA axis suppression → cannot stop abruptly (risk of adrenal crisis)
Infection	↑ susceptibility (TB reactivation - screen with IGRA before starting), PCP pneumonia (at high doses)
GI	Peptic ulcer (especially with NSAIDs), GI bleed
Ocular	Posterior subcapsular cataracts, Glaucoma
Psychiatric	Psychosis, Depression, Euphoria, Insomnia
Skin	Thin/fragile skin, Easy bruising, Poor wound healing

Stopping Steroids - HKMLE Trap

If on steroids >3 weeks or >5mg prednisolone/day → taper gradually (do NOT stop abruptly → adrenal insufficiency/crisis).

11. ADRENAL INSUFFICIENCY MANAGEMENT

Mnemonic: "ACE crisis = Addison's Cortisol Emergency = Hydrocortisone IM/IV now"

Adrenal Crisis (Emergency)

Feature	Detail
Presentation	Hypotension, hypoglycaemia, hyponatraemia, hyperkalaemia, fever, vomiting, altered GCS
Immediate treatment	Hydrocortisone 100mg IV bolus → then 50-100mg Q6h (or 200mg/day infusion)
Also give	IV 0.9% saline (large volumes), IV dextrose if hypoglycaemic
Do NOT delay steroids	Give before confirmatory tests if strongly suspected

Chronic Adrenal Insufficiency Replacement

Drug	Role	Dose Adjustment
Hydrocortisone	Glucocorticoid replacement	Standard: 15-25mg/day in 2-3 doses; double/triple dose during illness ("sick day rules")
Fludrocortisone	Mineralocorticoid replacement (primary AI only)	0.05-0.2mg/day

HKMLE Pearls:

Sick day rules: double hydrocortisone dose during fever/infection; if vomiting → IM/IV hydrocortisone

Pre-operative cover: patients on long-term steroids need stress-dose steroids perioperatively

Levothyroxine before steroids in combined pituitary failure = triggers adrenal crisis

12. BONE/METABOLISM DRUGS

12a. Bisphosphonates

Mnemonic: "BONE SNAP" = Bisphosphonate ONJ, Esophagitis, Snap fractures (atypical femur), Nephrological (avoid CKD)"

Feature	Detail
Mechanism	Bind hydroxyapatite → inhibit osteoclast activity → ↓ bone resorption → ↑ bone mineral density
Key Indications	Postmenopausal osteoporosis, Glucocorticoid-induced osteoporosis, Paget's disease (zoledronic acid), Hypercalcaemia of malignancy, Bone metastases (pain/fracture prevention)
Major Side Effects	Oesophagitis/oesophageal ulcers (oral - must stay upright 30-60 min after), Osteonecrosis of the jaw (ONJ) - especially with IV bisphosphonates + dental procedures, Atypical subtrochanteric femur fractures (long-term use), Acute phase reaction (IV: fever, myalgia, flu-like after first dose), Hypocalcaemia (IV)
Contraindications	eGFR <30-35 (renal clearance); Hypocalcaemia (correct first); Oesophageal disorders (oral forms)
HKMLE Paper	Paper I Medicine

Administration Rules for Oral Bisphosphonates (Exam-Tested)

Take on empty stomach with full glass of water (250mL)
Remain upright (sit/stand) for 30 minutes after (alendronate) or 60 minutes (risedronate)
No food or other medications for 30 minutes

Drug	Route	Frequency	Notes
Alendronate	Oral	Once weekly	Most widely used; osteoporosis
Risedronate	Oral	Once weekly or monthly
Ibandronate	Oral / IV	Monthly oral or 3-monthly IV
Zoledronic acid	IV	Once yearly	Highest potency; Paget's disease first-line; acute phase reaction
Pamidronate	IV	Variable	Hypercalcaemia of malignancy

12b. Denosumab

Mnemonic: "Denosumab DENoyes osteoclasts (RANK-L)"

Feature	Detail
Mechanism	Monoclonal antibody against RANK-L → prevents osteoclast formation and activity → ↓ bone resorption
Key Indications	Postmenopausal osteoporosis (especially when bisphosphonates not tolerated/contraindicated), Men with osteoporosis, Bone metastases (Xgeva - higher dose)
Major Side Effects	Hypocalcaemia (supplement Ca2+ + Vit D), ONJ (similar to bisphosphonates), Atypical femur fractures, Rebound vertebral fractures if stopped abruptly (transition to bisphosphonate!)
Contraindications	Hypocalcaemia, Pregnancy
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Unlike bisphosphonates, denosumab can be used in CKD (not renally cleared). However, hypocalcaemia risk is higher in CKD - supplement calcium. Never stop denosumab abruptly - rebound fractures; must transition to bisphosphonate.

12c. Calcitonin

Feature	Detail
Mechanism	Inhibits osteoclast activity → ↓ bone resorption; also ↓ renal calcium reabsorption
Key Indications	Acute hypercalcaemia (rapid-acting, used short-term), Paget's disease, Osteoporosis (limited use now), Acute pain from vertebral osteoporotic fracture (intranasal)
Major Side Effects	Nausea, Flushing, Nasal irritation (intranasal), Tachyphylaxis (tolerance within days)
HKMLE Paper	Paper I Medicine

HKMLE Pearl: In hypercalcaemia of malignancy → IV bisphosphonate (zoledronic acid) is superior; calcitonin used for immediate/rapid effect while bisphosphonate takes 2-4 days to work.

12d. PTH Analogues (Anabolic Bone Agents)

Drug	Mechanism	Indication	Key Side Effect
Teriparatide (recombinant PTH 1-34)	Stimulates osteoblasts → bone formation (anabolic) when given intermittently (paradox: continuous PTH = resorption; pulsed = formation)	Severe osteoporosis with fractures; patients failing bisphosphonate	Nausea, Leg cramps, Hypercalcaemia; Contraindicated in Paget's, prior radiation, bone mets, hyperPTH
Abaloparatide	PTH-related protein analogue	Severe postmenopausal osteoporosis	Similar to teriparatide
Romosozumab	Anti-sclerostin antibody → ↑ bone formation + ↓ resorption	Severe osteoporosis at high fracture risk	CV risk (↑ MI/stroke) - avoid in prior CV events

HKMLE Pearl: Teriparatide is anabolic (forms bone) - unlike bisphosphonates/denosumab which are antiresorptive. Maximum use = 2 years (lifetime limit).

13. PITUITARY DRUGS

13a. Desmopressin (DDAVP)

Mnemonic: "DDAVP = Dry the tap (antidiuretic) without the pressure (no vasoconstriction)"

Feature	Detail
Mechanism	Synthetic V2-receptor agonist (vasopressin analogue) → ↑ water reabsorption in collecting duct (no V1 pressor effect)
Key Indications	Central diabetes insipidus (treatment of choice), Nocturnal enuresis (children), von Willebrand disease type 1 (↑ vWF release), Haemophilia A (↑ Factor VIII), Bedwetting
Major Side Effects	Hyponatraemia/water intoxication (most important - especially in children), Headache, Nausea; Flushing
Contraindications	Nephrogenic DI (kidneys don't respond to ADH), Psychogenic polydipsia, Severe hyponatraemia
HKMLE Paper	Paper I Medicine, Paper III Paediatrics

HKMLE Pearl: Central DI = low urine osmolality + high serum osmolality → responds to desmopressin (water deprivation test confirms). Nephrogenic DI = no response to desmopressin → treat with thiazide diuretics (paradoxical).

13b. Somatostatin Analogues

Mnemonic: "OctREOtide = Octopus grabs all the excess hormones"

Feature	Detail
Mechanism	Mimic somatostatin → inhibit GH, insulin, glucagon, TSH, and gut hormone secretion; reduce splanchnic blood flow
Key Indications	Acromegaly (post-surgical, when surgery fails), Carcinoid syndrome (symptom control), Variceal bleeding (↓ portal pressure), Glucagonoma/VIPoma/gastrinoma, TSH-secreting pituitary tumour
Major Side Effects	GI (nausea, diarrhoea, malabsorption), Gallstones (↓ gallbladder motility), Hyperglycaemia or hypoglycaemia, Bradycardia
HKMLE Paper	Paper I Medicine

Key drugs: Octreotide (short-acting SC/IV), Lanreotide, Pasireotide (depot monthly)

13c. Other Pituitary Drugs

Drug	Indication	Key Points
Cabergoline / Bromocriptine	Prolactinoma (first-line), Acromegaly (adjunct), Parkinson's (bromocriptine)	Dopamine D2 agonist → ↓ prolactin; Cabergoline preferred (once/twice weekly; better tolerated). SE: nausea, postural hypotension, cardiac valve fibrosis (high dose)
Pegvisomant	Acromegaly resistant to somatostatin analogues	GH receptor antagonist → ↓ IGF-1; monitor LFTs
Lanreotide / Octreotide	Acromegaly, Carcinoid	See somatostatin above
GnRH agonists (Leuprolide, Goserelin)	Prostate cancer, Endometriosis, Precocious puberty	Continuous use → paradoxically ↓ LH/FSH (downregulate receptors); SE: hot flushes, osteoporosis
Desmopressin	Central DI, vWD, Enuresis	See above
Growth hormone (Somatropin)	GH deficiency in children/adults, Turner syndrome, Prader-Willi	SE: Fluid retention, Insulin resistance, Intracranial hypertension (in children), Acromegaly features if overdosed

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
Metformin contraindications (eGFR, contrast)	Paper I Medicine	Contraindication scenario
SGLT2i in HF / CV benefit	Paper I Medicine	Indication selection
GLP-1 MTC contraindication	Paper I Medicine	Contraindication MCQ
Insulin types (IV capable, onset/peak)	Paper I Medicine / Paper III	Practical management
Sulfonylurea hypoglycaemia in elderly	Paper I Medicine	Drug choice / complication
Thyroid drugs in pregnancy (PTU vs carbimazole)	Paper I / Paper III OG	Safe prescribing in pregnancy
Antithyroid → agranulocytosis	Paper I Medicine	Monitoring / complication
Thyroid storm management	Paper II Emergency	Emergency management protocol
Adrenal crisis (hydrocortisone IV)	Paper II Emergency	Emergency treatment
Bisphosphonate administration rules / ONJ	Paper I Medicine	Side effect / counselling
Denosumab vs bisphosphonate (CKD)	Paper I Medicine	Drug choice in CKD
Desmopressin in central DI	Paper I Medicine	Mechanism/indication
Corticosteroid side effects	Paper I Medicine	Complication identification
Teriparatide (anabolic mechanism)	Paper I Medicine	Mechanism MCQ

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
Metformin contraindications	CRASH = CKD (eGFR <30), Radiological contrast (48h hold), Alcoholism, Serious illness/surgery, Hepatic failure
SGLT2i side effects	FUNGUS = Female genital mycosis, UTI, Nocturia/diuresis, Glycosuria, Urinary frequency, Skin (Fournier's)
GLP-1 contraindication	MEN = MTC history + Endocrine Neoplasia type 2
Corticosteroid side effects	STEROIDS = Sugar↑, Thin skin/bones, Edema, Raised BP, Obesity, Infections, Delayed healing, Suppression HPA
PTU vs Carbimazole in pregnancy	"PTU = 1st trimester, Carbimazole/Methimazole = after" (PTU safer in T1; switch at T2 - PTU hepatotoxic)
Bisphosphonate counselling	STOP EAT = Stay upright, Take on empty stomach, Only water with tablet, Pre-dental check (ONJ risk)
Adrenal crisis treatment	"HISS" = Hydrocortisone IV, IV saline, Sugar (dextrose), Support vitals
Insulin only IV	"Regular Goes IV" - only Regular (short-acting) and rapid analogs (not NPH, not glargine)

Sources: Lippincott Illustrated Reviews Pharmacology; Goodman & Gilman's Pharmacological Basis of Therapeutics; Harrison's Principles of Internal Medicine 22E (2025); Brenner & Rector's The Kidney; Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology 16th Edition.

Give me high-yield HKMLE notes on Antibiotics & Antifungals with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - Penicillins (natural, aminopenicillins, anti-staphylococcal, antipseudomonal) - Cephalosporins (generations 1-5 + key coverage differences) - Carbapenems and monobactams (aztreonam) - Macrolides - Quinolones (fluoroquinolones) - Aminoglycosides - Tetracyclines - Glycopeptides (vancomycin, teicoplanin) - Metronidazole - Oxazolidinones (linezolid) - Antifungals (azoles, echinocandins, amphotericin B, flucytosine) - Key drug interactions and toxicities (e.g., warfarin + antibiotics) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Cardio notes.

Reading File

Finding Sources

Reading File

I now have all the core data. I have enough from Lippincott, Harrison's, and Sherris microbiology to compile a complete, accurate set of notes. Let me write them out now.

High-Yield HKMLE: Antibiotics & Antifungals Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): Drug mechanisms, resistance patterns, toxicities, drug interactions, infection management

Paper II Surgery/Emergency (45 MCQs): Surgical prophylaxis, wound infections, sepsis antibiotic choices, C. difficile

Paper III Paediatrics/OG (30 MCQs): Antibiotics safe/unsafe in pregnancy, neonatal infections

MASTER MECHANISM TABLE

Mnemonic: "CATCH ME" = Cell wall, Aminoglycosides (protein 30S), Tetracyclines (30S), Cell membrane, macrolides/linezolid (50S), Metronidazole (DNA), quinolonEs (DNA gyrase)

Target	Drug Class
Cell wall synthesis	β-lactams (penicillins, cephalosporins, carbapenems, aztreonam), Glycopeptides (vancomycin)
30S ribosome	Aminoglycosides, Tetracyclines
50S ribosome	Macrolides, Clindamycin, Chloramphenicol, Linezolid
DNA gyrase / Topoisomerase IV	Fluoroquinolones
DNA damage	Metronidazole
Cell membrane	Polymyxins (colistin), Daptomycin
Folate synthesis	Sulfonamides
Folate reduction	Trimethoprim

1. PENICILLINS

Mnemonic: "Penicillins Prevent Peptidoglycan Production - Prone to Penicillinase"

Feature	Detail
Mechanism	Bind penicillin-binding proteins (PBPs) → inhibit transpeptidation → ↓ cell wall cross-linking → bactericidal (time-dependent killing)
Resistance	β-lactamase (penicillinase) production; altered PBPs (MRSA)
Class side effects (all)	Hypersensitivity/allergy (rash → anaphylaxis - most important), GI upset, C. difficile colitis
HKMLE Paper	Paper I, II, III

Penicillin Sub-classes

Sub-class	Drugs	Coverage	Key Use	Key Points
Natural	Benzylpenicillin (Pen G, IV), Phenoxymethylpenicillin (Pen V, oral)	Streptococci, Neisseria, Treponema, Clostridia	Strep throat, Syphilis, Bacterial endocarditis prophylaxis	Narrow spectrum; acid-labile (Pen G must be IV)
Aminopenicillins	Amoxicillin, Ampicillin	Broad gram+ and gram- (H. flu, E. coli, Listeria); NO Pseudomonas	CAP (amoxicillin), UTI, Otitis media, Listeria meningitis	Amoxicillin = most prescribed antibiotic globally
β-lactam/β-lactamase inhibitor combos	Co-amoxiclav (amoxicillin + clavulanate), Tazocin (piperacillin-tazobactam)	Broader: MSSA, anaerobes, some gram-negatives	CAP, HAP, Intra-abdominal, Surgical infections	Clavulanate = β-lactamase inhibitor; Tazocin = anti-pseudomonal
Anti-staphylococcal	Flucloxacillin, Methicillin (historical), Nafcillin	MSSA ONLY; NOT MRSA	Cellulitis, MSSA bacteraemia, Skin/soft tissue	Penicillinase-resistant; flucloxacillin = drug of choice for MSSA
Antipseudomonal	Piperacillin (+ tazobactam), Ticarcillin	Broad gram-negative incl. Pseudomonas	HAP, VAP, Febrile neutropenia, Severe sepsis	Must pair with β-lactamase inhibitor

HKMLE Pearls:

Penicillin allergy cross-reactivity with cephalosporins: ~1-2% (not 10% as historically cited) - major allergy (anaphylaxis) = avoid all β-lactams; minor rash = cephalosporins usually safe

Flucloxacillin = MSSA only (not MRSA); absorbed poorly with food (take 30 min before)

Ampicillin rash in EBV (mononucleosis) = non-allergic maculopapular rash (NOT true penicillin allergy!)

Co-amoxiclav hepatotoxicity - cholestatic jaundice (especially in elderly males, prolonged course)

2. CEPHALOSPORINS

Mnemonic: "GAPS get Bigger with generation - 1st = MSSA/Strep; 5th = MRSA"

Generation	Key Coverage	Key Drugs	Key Indications
1st	Gram+ (MSSA, Strep), some gram- (E. coli, Klebsiella)	Cefalexin (oral), Cefazolin (IV)	Surgical prophylaxis (gold standard), Skin/soft tissue, UTI
2nd	Gram+ + more gram- (H. influenzae); some anaerobes	Cefuroxime, Cefoxitin	RTI, Sinusitis, Surgical prophylaxis (colorectal = cefoxitin)
3rd	Predominantly gram-negative; CNS penetration; anti-pseudomonal: ceftazidime	Ceftriaxone, Cefotaxime, Ceftazidime	Meningitis (ceftriaxone), Sepsis, Gonorrhoea, Typhoid
4th	Broad gram+ and gram-; anti-pseudomonal	Cefepime	HAP, Febrile neutropenia, Pseudomonas infections
5th	MRSA coverage; broad gram+ and gram-	Ceftaroline	MRSA skin/soft tissue; CAP

HKMLE Pearls:

Ceftriaxone = 3rd gen; drug of choice for bacterial meningitis (empirical with ampicillin for Listeria cover), gonorrhoea (IM single dose), typhoid fever in severe cases

No cephalosporin covers MRSA except ceftaroline (5th gen)

No cephalosporin reliably covers Enterococcus (use penicillin/vancomycin)

Ceftazidime = only 3rd gen with anti-pseudomonal activity

Side effects: C. difficile colitis; cross-allergy with penicillin (small risk); ceftriaxone → biliary sludge/pseudolithiasis

3. CARBAPENEMS

Mnemonic: "Carbapenems = Carpet-bomb everything (widest β-lactam spectrum) - but NOT MRSA"

Feature	Detail
Mechanism	Same as penicillins (PBP binding → cell wall synthesis inhibition) but resistant to most β-lactamases
Coverage	Extremely broad: gram+, gram-, anaerobes, Pseudomonas (imipenem/meropenem); NOT MRSA, Stenotrophomonas
Key Indications	MDR gram-negative sepsis, HAP/VAP, Febrile neutropenia, Intra-abdominal sepsis, Meningitis (meropenem)
Major Side Effects	Imipenem → seizures (lowest threshold; avoid in CNS infection); Nausea/vomiting, Hypersensitivity, C. difficile
HKMLE Paper	Paper I Medicine, Paper II Surgery

Drug	Key Point
Imipenem-cilastatin	Cilastatin prevents renal metabolism of imipenem; causes seizures
Meropenem	Fewer seizures than imipenem; preferred for meningitis
Ertapenem	Once daily but NO Pseudomonas or Acinetobacter coverage
Doripenem	Broad, anti-pseudomonal

HKMLE Pearl: Carbapenem-resistant Enterobacteriaceae (CRE) = KPC-producing Klebsiella → treat with colistin/polymyxin B or newer agents (ceftazidime-avibactam). Classic exam scenario.

4. AZTREONAM (Monobactam)

Feature	Detail
Mechanism	β-lactam; binds PBP3 of gram-negative bacteria only
Coverage	Gram-negative only (aerobic, including Pseudomonas); NO gram+, NO anaerobes
Key Indications	Gram-negative infections in penicillin/cephalosporin-allergic patients; UTI, respiratory, septicaemia
Side Effects	Well tolerated; minimal cross-reactivity with other β-lactams
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Safe alternative to β-lactams in severe penicillin allergy for gram-negative infections. No activity against gram-positive organisms.

5. GLYCOPEPTIDES - Vancomycin & Teicoplanin

Mnemonic: "VanCOMycin = VAN for MRSA, COM-plications: Red man, neCROsis (nephro/oto)"

Feature	Vancomycin	Teicoplanin
Mechanism	Binds D-Ala-D-Ala terminus of peptidoglycan precursors → inhibits cell wall synthesis (different site from β-lactams)	Same mechanism
Coverage	Gram-positive only: MRSA, MSSA, Enterococcus, Streptococcus, C. difficile (oral only = non-systemic)	Same
Key Indications	MRSA bacteraemia/endocarditis/pneumonia; C. difficile (oral, not absorbed) when metronidazole fails; MRSA meningitis (intrathecal)	MRSA, Gram+ bone/joint infections
Major Side Effects	"Red man syndrome" (histamine release with rapid infusion → flushing, rash, hypotension - not true allergy, slow infusion prevents it), Nephrotoxicity (especially with aminoglycosides), Ototoxicity (tinnitus → hearing loss), Thrombophlebitis	Better tolerated than vancomycin; once daily dosing
Monitoring	Trough levels (target 10-15 µg/mL; 15-20 for MRSA bacteraemia/endocarditis); AUC/MIC preferred	Trough levels
Contraindications	Vancomycin-resistant Enterococcus (VRE) - use linezolid/daptomycin	-
HKMLE Paper	Paper I Medicine, Paper II Surgery

HKMLE Pearls:

Oral vancomycin = stays in gut → C. difficile treatment (NOT absorbed systemically)

IV vancomycin = systemic infections (MRSA)

Red man syndrome = slow the infusion rate + antihistamine before infusion

Vancomycin + aminoglycoside = synergistic nephrotoxicity (avoid combination)

6. AMINOGLYCOSIDES

Mnemonic: "AMINO = Always Monitor (nephro/oto toxic), Never Once without Oxygen (aerobes only), Inject IV"

Feature	Detail
Mechanism	Bind 30S ribosomal subunit → misreading of mRNA → abnormal protein synthesis → bactericidal; concentration-dependent killing
Coverage	Aerobic gram-negative bacilli (E. coli, Klebsiella, Pseudomonas); synergy with β-lactams/vancomycin for Enterococcus, Streptococcus endocarditis; NO anaerobes (require O2 for uptake)
Key Indications	Gram-negative sepsis (with β-lactam), Pseudomonas, Endocarditis (synergy), Plague (streptomycin), TB (streptomycin)
Major Side Effects	Nephrotoxicity (most common - monitor creatinine), Ototoxicity (vestibular and cochlear - irreversible!), Neuromuscular blockade (rare - caution in myasthenia gravis)
Contraindications	Myasthenia gravis, Pregnancy (streptomycin = ototoxic to fetus), Concurrent nephrotoxins
Monitoring	Peak + trough levels; once-daily dosing (extended interval) preferred to reduce toxicity
HKMLE Paper	Paper I Medicine, Paper II Surgery

Drug	Key Use
Gentamicin	Most common; broad gram-negative; endocarditis synergy
Amikacin	Reserved for gentamicin-resistant organisms
Tobramycin	Pseudomonas; inhaled for cystic fibrosis
Streptomycin	TB, Plague, Brucella
Neomycin	Topical only (otic/optic); bowel decontamination pre-surgery

HKMLE Pearls:

Ototoxicity = irreversible (both cochlear = hearing loss AND vestibular = balance problems)

Aminoglycosides + loop diuretics (furosemide) = ↑ ototoxicity risk

Aminoglycosides + vancomycin = ↑ nephrotoxicity

Do NOT use in anaerobic infections (no O2 → drug not taken up)

7. MACROLIDES

Mnemonic: "MAcrolides = Motility promoters, Atypical cover, CYP inhibitors"

Feature	Detail
Mechanism	Bind 50S ribosomal subunit (23S rRNA) → inhibit translocation → bacteriostatic (bactericidal at high doses)
Coverage	Gram+ (Strep, MSSA), Atypicals (Mycoplasma, Chlamydia, Legionella), H. pylori (clarithromycin), Mycobacteria, Bordetella pertussis
Key Indications	CAP (atypical cover), Atypical pneumonia (first-line), H. pylori (triple therapy - clarithromycin), Pertussis, STIs (chlamydia - azithromycin), MAC prophylaxis/treatment (HIV)
Major Side Effects	GI (nausea, diarrhoea, cramping; erythromycin most), QT prolongation (all macrolides), Cholestatic jaundice (erythromycin estolate), Ototoxicity (high-dose erythromycin), Drug interactions (CYP3A4 inhibitors - ↑ warfarin, statins, cyclosporin levels)
Contraindications	Prolonged QT, Concurrent QT-prolonging drugs, Hepatic failure
HKMLE Paper	Paper I Medicine, Paper III OG

Drug	Key Points
Erythromycin	Original; GI prokinetic effect (used for gastroparesis); most drug interactions; erythromycin estolate → cholestatic jaundice (avoid in pregnancy)
Clarithromycin	H. pylori triple therapy; CAP; MAC; twice daily; strongest CYP inhibitor of the class
Azithromycin	Once daily; long t½ (tissue accumulation); Chlamydia (single dose 1g); fewest drug interactions; Z-pack (5-day course)

HKMLE Pearls:

Clarithromycin + warfarin = ↑ INR (CYP3A4 inhibition) - classic exam interaction

Clarithromycin + statins (simvastatin) = rhabdomyolysis risk

Erythromycin safe in pregnancy; azithromycin also generally safe; clarithromycin avoid in pregnancy (teratogenic in animal studies)

QT prolongation: azithromycin > erythromycin > clarithromycin (all prolong)

8. FLUOROQUINOLONES

Mnemonic: "FLOX = Football (tendon), Liver (hepatotoxicity), QT prolongation, X-linked issues (avoid in children)"

Feature	Detail
Mechanism	Inhibit DNA gyrase (gram-negative) and Topoisomerase IV (gram-positive) → prevent DNA replication → bactericidal (concentration-dependent)
Coverage	Broad gram-negative (Pseudomonas - ciprofloxacin, levofloxacin), Atypicals, Gram+ (respiratory quinolones: levofloxacin, moxifloxacin), TB (second-line)
Key Indications	UTI/pyelonephritis (ciprofloxacin), Typhoid fever, Traveller's diarrhoea, Pseudomonas, CAP (levofloxacin, moxifloxacin), TB (second-line), Anthrax
Major Side Effects	Tendinopathy/tendon rupture (Achilles most common; risk ↑ with steroids, elderly, renal failure), QT prolongation, CNS effects (insomnia, seizures, dizziness), C. difficile colitis, Photosensitivity, GI upset
Contraindications	Children/growing cartilage (relative; risk of arthropathy), Pregnancy and lactation, Concurrent QT-prolonging drugs, Epilepsy (lower seizure threshold), History of tendinopathy
HKMLE Paper	Paper I Medicine, Paper II Surgery

Drug	Gram+	Gram- (Pseudo)	Atypical	Key Use
Ciprofloxacin	-	+++ (best anti-Pseudo)	+	UTI, Pseudomonas, Typhoid, Traveller's diarrhoea
Levofloxacin	++	++	+++	CAP (respiratory FQ), UTI, Pseudomonas
Moxifloxacin	+++	+ (NO Pseudomonas)	+++	CAP, Intra-abdominal; TB (second-line); not for UTI (low urinary excretion)

HKMLE Pearls:

Tendon rupture risk ↑ with concomitant steroids - classic exam combination

C. difficile risk is HIGH with fluoroquinolones (alongside cephalosporins and clindamycin)

Moxifloxacin has NO urinary activity → not for UTI (absorbed hepatically)

Ciprofloxacin inhibits CYP1A2 → ↑ theophylline levels (toxicity!) - key drug interaction

9. TETRACYCLINES

Mnemonic: "TETRACYCLE = Teeth stain, Embryo harm, Treats atypicals, Rickettsiae, Acne, C. pylori (triple therapy historically), Young children avoid, Cross BBB, Light sensitivity, Esophageal irritation"

Feature	Detail
Mechanism	Bind 30S ribosome → block aminoacyl-tRNA binding → inhibit protein synthesis → bacteriostatic
Coverage	Atypicals (Mycoplasma, Chlamydia, Rickettsia, Coxiella), Brucella, Spirochaetes (Borrelia/Lyme, Syphilis), Vibrio, H. pylori, MRSA (doxycycline), Malaria prophylaxis (doxycycline)
Key Indications	Atypical CAP, Chlamydia (2nd line after azithromycin), Lyme disease, Rickettsia (Rocky Mountain spotted fever - DOC!), Brucellosis, Acne, Malaria prophylaxis, MRSA skin infections (doxycycline)
Major Side Effects	Teeth discolouration and enamel hypoplasia (children <8 years), Teratogen (bone/teeth deformity), Photosensitivity, Oesophageal ulceration (take with full glass of water, remain upright), GI upset, Hepatotoxicity (IV high-dose), Pseudotumour cerebri (↑ ICP)
Contraindications	Children <8 years (dental/bone effects), Pregnancy (Category D), Breastfeeding, Renal failure (doxycycline = exception; hepatically eliminated, safe in CKD)
HKMLE Paper	Paper I Medicine, Paper III OG/Paediatrics

Drug	Notes
Doxycycline	Most used; once or twice daily; safe in renal failure (hepatic elimination); malaria prophylaxis
Tetracycline	4x daily; avoid in renal failure; food ↓ absorption (antacids, dairy)
Minocycline	CNS side effects (vertigo, dizziness); acne; MRSA
Tigecycline	IV only; broadest tetracycline coverage; MDR gram-negative + anaerobes; NOT Pseudomonas

HKMLE Pearl: Rickettsia (RMSF, typhus) = doxycycline is DOC even in children (risk of serious disease outweighs dental risk). The dental rule is relaxed for Rocky Mountain Spotted Fever.

10. METRONIDAZOLE

Mnemonic: "METRO = Must avoid alcohol, Then DNA damaged (anaerobes), Reduces warfarin levels up (inhibits CYP), Obese bugs and protozoa killed"

Feature	Detail
Mechanism	Prodrug activated by bacterial/protozoal nitroreductases → forms reactive intermediates → DNA strand breaks → bactericidal
Coverage	Obligate anaerobes (Bacteroides fragilis, Clostridium), Protozoa (Giardia, Entamoeba, Trichomonas)
Key Indications	C. difficile (oral; first/second-line), Intra-abdominal infections (anaerobic cover, with cephalosporin/fluoroquinolone), Bacterial vaginosis, Trichomonas, Giardia, Amoebiasis, H. pylori (triple therapy), Dental infections
Major Side Effects	Metallic taste (very common), Nausea, Peripheral neuropathy (prolonged use), CNS effects (seizures, encephalopathy at high doses), Disulfiram-like reaction with alcohol (acetaldehyde accumulation → flushing, vomiting)
Contraindications	First trimester pregnancy (potential teratogenicity), Alcohol consumption during treatment
HKMLE Paper	Paper I Medicine, Paper II Surgery

HKMLE Pearls:

Metronidazole + alcohol = disulfiram-like reaction (also triggered by mouthwashes with alcohol)

Metronidazole + warfarin = ↑ INR (inhibits CYP2C9 → ↑ warfarin effect) - classic exam interaction

Does NOT cover aerobic bacteria; always use with broad-spectrum antibiotic in mixed infections

C. difficile: mild/moderate = oral metronidazole; severe = oral vancomycin (fidaxomicin if available)

11. LINEZOLID (Oxazolidinone)

Mnemonic: "LINEZOLID = Last resort, Inhibits 50S, No MAO (MAOI activity), Expensive, Zaps MRSA/VRE, Orange-ish (serotonin), Lowers platelet count, Inhibits bone marrow"

Feature	Detail
Mechanism	Binds 50S ribosomal subunit (unique site: 23S rRNA-peptidyl transferase centre) → prevents formation of 70S initiation complex → bacteriostatic (bactericidal vs Streptococcus)
Coverage	Gram-positive only: MRSA, VRE (Vancomycin-Resistant Enterococcus), Drug-resistant Streptococcus, MSSA (backup)
Key Indications	MRSA pneumonia/skin infections (when vancomycin fails or poor lung penetration), VRE infections, MDR-TB (second-line)
Major Side Effects	Myelosuppression (thrombocytopaenia most common → monitor FBC weekly for courses >2 weeks), Serotonin syndrome (weak MAO inhibitor - do NOT combine with SSRIs/SNRIs/tramadol), Peripheral neuropathy (long-term), Optic neuritis
Contraindications	Concurrent serotonergic drugs (SSRIs, MAOIs, tramadol), Uncontrolled HTN (mild pressor effect)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Linezolid is a reversible MAO inhibitor → serotonin syndrome if combined with SSRIs

Oral bioavailability = 100% (oral = IV efficacy; allows step-down from IV)

Daptomycin is alternative for MRSA/VRE but inactivated by surfactant → NOT for pneumonia (use linezolid for MRSA lung infection)

12. CLINDAMYCIN

Feature	Detail
Mechanism	Binds 50S ribosome → blocks translocation → bacteriostatic
Coverage	Gram+ (Strep, MSSA, some MRSA), Anaerobes (above diaphragm - Bacteroides), Toxoplasma (with pyrimethamine)
Key Indications	Aspiration pneumonia (anaerobic cover), Dental infections, MSSA skin/soft tissue, Toxoplasmosis, Malaria (adjunct), Osteomyelitis
Major Side Effects	C. difficile colitis (highest risk of all antibiotics), Diarrhoea, GI upset, Antibiotic-associated colitis
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Clindamycin + C. difficile = highest-risk combination (classic exam association). Always warn patients to report diarrhoea immediately.

13. CO-TRIMOXAZOLE (Trimethoprim + Sulfamethoxazole)

Feature	Detail
Mechanism	Sequential block of folate synthesis: sulfamethoxazole inhibits dihydropteroate synthase; trimethoprim inhibits dihydrofolate reductase → synergistic bactericidal effect
Coverage	Gram+ and gram-, PCP (Pneumocystis jirovecii), Toxoplasma, Nocardia, MRSA (community-acquired)
Key Indications	PCP prophylaxis and treatment (HIV/immunocompromised - first-line), UTI, MRSA skin infections (community), Nocardia, Toxoplasma (with pyrimethamine), Traveller's diarrhoea
Major Side Effects	Stevens-Johnson syndrome (SJS/TEN - sulfa component), Myelosuppression (folate antagonism → megaloblastic anaemia), Hyperkalaemia (trimethoprim blocks ENaC = like amiloride), Nausea, Photosensitivity, Crystalluria
Contraindications	Severe renal impairment, Pregnancy (folate antagonism → neural tube defects; give folic acid), G6PD deficiency (haemolysis)
HKMLE Paper	Paper I Medicine, Paper III

HKMLE Pearl: Hyperkalaemia with TMP-SMX = trimethoprim blocks potassium excretion in collecting duct (amiloride-like effect). Classic trap in patients on ACEi/ARBs.

14. ANTIFUNGALS

14a. Amphotericin B (Polyene)

Mnemonic: "Ampho-TERRIBLE = Terrible side effects but Terrific spectrum"

Feature	Detail
Mechanism	Binds ergosterol in fungal cell membrane → forms pores → K+ leakage → cell death (fungicidal)
Coverage	Broadest antifungal: Candida, Aspergillus, Cryptococcus, Mucor, Histoplasma, Coccidioides, Blastomyces; also Leishmaniasis
Key Indications	Severe/life-threatening systemic fungal infections (Cryptococcal meningitis, Invasive aspergillosis, Mucormycosis, Systemic candidiasis when azoles fail)
Major Side Effects	"Shake and bake" (rigors + fever during infusion), Nephrotoxicity (hypokalaemia, hypomagnesaemia, renal tubular acidosis - most dose-limiting), Anaemia (↓ EPO), Thrombophlebitis
Reduce toxicity	Lipid formulations (liposomal amphotericin B = AmBisome) - same efficacy, much less nephrotoxicity; premedicate with paracetamol + antihistamine + hydrocortisone for infusion reactions
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Always correct hypokalaemia and hypomagnesaemia during treatment (wasting nephropathy)

Liposomal preparation = reduces nephrotoxicity, preferred in renal impairment

Fungal resistance = ↓ ergosterol content in cell membrane

14b. Azole Antifungals

Mnemonic: "AZOLES = All inhibit CYP (P450), Zero gram+/gram- activity, Only fungi, Liver monitoring, Ergosterol synthesis blocked"

Feature	Detail
Mechanism	Inhibit fungal CYP51 (lanosterol 14α-demethylase) → ↓ ergosterol synthesis → ↑ methylated sterols → altered membrane function → fungistatic
Side effects (class)	Hepatotoxicity (monitor LFTs), Drug interactions (all inhibit CYP3A4 → ↑ warfarin, statins, tacrolimus, cyclosporin, benzodiazepines)

Azole Comparison Table

Drug	Spectrum	Route	Key Indication	Unique Points
Fluconazole	Narrow (Candida, Cryptococcus)	Oral/IV	Oropharyngeal candidiasis, Vulvovaginal candidiasis, Cryptococcal meningitis (maintenance), Prophylaxis in neutropenia	CSF penetration (good); safe in pregnancy for single-dose vaginal candidiasis; renal elimination; NOT Aspergillus
Itraconazole	Broad (+ Aspergillus, Histoplasma)	Oral	Histoplasmosis, Sporotrichosis, Onychomycosis, Dermatophytes	Negative inotrope (↓ cardiac contractility) - AVOID in HF
Voriconazole	Very broad (+ Aspergillus, Fusarium)	Oral/IV	Invasive aspergillosis (first-line), Fusariosis, Serious Candida infections	Visual disturbances (hallucinations, photopsia) - unique; hepatotoxicity; monitor TDM
Posaconazole	Broadest (+ Mucor/Rhizopus)	Oral/IV	Mucormycosis, Prophylaxis in AML/HSCT, Refractory aspergillosis	Broadest oral azole; TDM required; take with food
Isavuconazole	Very broad (+ Mucor)	Oral/IV	Invasive aspergillosis and mucormycosis	Better GI tolerability than posaconazole; long t½

HKMLE Pearls:

Fluconazole does NOT cover Aspergillus (classic exam trap)

Voriconazole = first-line for invasive aspergillosis

Posaconazole/isavuconazole = mucormycosis (Mucor/Rhizopus - Zygomycetes) - fluconazole/voriconazole NOT effective against Mucor

All azoles ↑ warfarin → check INR; ↑ statin levels → rhabdomyolysis risk; ↑ tacrolimus/cyclosporin → toxicity

Itraconazole negative inotrope → contraindicated in heart failure

14c. Echinocandins

Mnemonic: "Echinocandins = Echo = They WALL off fungi (cell wall)"

Feature	Detail
Mechanism	Inhibit β-1,3-glucan synthase → ↓ fungal cell wall synthesis (unique target → broad safety profile)
Coverage	Candida (including azole-resistant, including C. glabrata and C. krusei), Aspergillus (not first-line); NOT Cryptococcus, NOT Mucor
Key Indications	Invasive candidiasis (first-line in ICU/neutropenia), Candidaemia, Oesophageal candidiasis, Salvage for Aspergillus
Major Side Effects	Generally very well tolerated; Infusion reactions (rare), Elevated liver enzymes, Histamine release
Contraindications	Not for Cryptococcus or Mucormycosis (no activity)
HKMLE Paper	Paper I Medicine

Drug	Notes
Caspofungin	First approved; most studied
Micafungin	Once daily; few drug interactions
Anidulafungin	Hepatically degraded (not metabolised by CYP); safe in liver disease

HKMLE Pearl: Echinocandins are IV only (no oral formulation available). First-line for invasive candidiasis in haemodynamically unstable or azole-exposed patients.

14d. Flucytosine (5-Fluorocytosine)

Feature	Detail
Mechanism	Converted to 5-fluorouracil (5-FU) inside fungal cells → inhibits DNA/RNA synthesis
Coverage	Candida, Cryptococcus; used in combination (resistance rapidly develops with monotherapy)
Key Indications	Cryptococcal meningitis (with amphotericin B - synergistic combination), Candida endocarditis/meningitis
Side Effects	Myelosuppression (leucopenia, thrombocytopaenia), GI upset, Hepatotoxicity - monitor FBC and LFTs
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Flucytosine is never used alone (rapid resistance). Classic combination = amphotericin B + flucytosine for Cryptococcal meningitis (2-week induction phase).

KEY DRUG INTERACTIONS - HIGH YIELD TABLE

Antibiotic	Interacting Drug	Effect	Mechanism
Metronidazole	Warfarin	↑ INR (bleeding risk)	Inhibits CYP2C9
Metronidazole	Alcohol	Disulfiram reaction (flushing, vomit, hypotension)	Blocks ALDH
Clarithromycin/Erythromycin	Warfarin	↑ INR	CYP3A4 inhibition
Clarithromycin	Simvastatin	Rhabdomyolysis	CYP3A4 inhibition → ↑ statin
Ciprofloxacin	Theophylline	↑ Theophylline toxicity (arrhythmia, seizures)	CYP1A2 inhibition
Ciprofloxacin	Warfarin	↑ INR	CYP1A2 inhibition
Fluconazole	Warfarin	↑ INR (significantly)	CYP2C9 inhibition
Fluconazole	Tacrolimus/Cyclosporin	Toxicity (nephrotoxicity)	CYP3A4 inhibition
Rifampicin	Warfarin, OCP, ART, Tacrolimus	↓ Efficacy (treatment failure)	CYP450 induction
Tetracyclines	Antacids/Milk/Iron	↓ Absorption of tetracycline (chelation)	Divalent cation chelation
Aminoglycosides	Furosemide (loop diuretics)	↑ Ototoxicity	Additive toxicity
Aminoglycosides	Vancomycin	↑ Nephrotoxicity	Additive
Linezolid	SSRIs/Tramadol	Serotonin syndrome	MAO inhibition

ANTIBIOTICS IN PREGNANCY

Mnemonic: "SAFE MOM = Safest: Penicillins, Azithromycin, FEw cephalosporins, Erythromycin base, Metronidazole (avoid T1)"

Safe in Pregnancy	Avoid in Pregnancy	Reason to Avoid
Penicillins (all)	Tetracyclines	Teeth/bone - maternal hepatotoxicity
Cephalosporins	Fluoroquinolones	Cartilage/tendon effects
Azithromycin	Aminoglycosides (streptomycin)	Fetal ototoxicity
Erythromycin base	Chloramphenicol	Grey baby syndrome (near term)
Metronidazole (avoid T1)	Trimethoprim (T1)	Folate antagonism - neural tube defects
Nitrofurantoin (avoid near term)	Co-trimoxazole (T1, near term)	G6PD haemolysis at term
Clindamycin	Erythromycin estolate	Cholestatic hepatitis

ANTIBIOTIC COVERAGE CHEAT SHEET

Organism	First-Line Drug
MRSA	Vancomycin IV (bacteraemia/serious); Doxycycline/TMP-SMX (skin/community)
VRE	Linezolid or Daptomycin
Pseudomonas aeruginosa	Pip-tazo, Ceftazidime, Cefepime, Meropenem, Ciprofloxacin
C. difficile (mild)	Oral metronidazole or Oral vancomycin
C. difficile (severe)	Oral vancomycin or Fidaxomicin
ESBL gram-negative	Meropenem (or ertapenem if non-Pseudomonas)
Cryptococcal meningitis	Amphotericin B + Flucytosine (induction 2w) → Fluconazole (consolidation)
Invasive Aspergillosis	Voriconazole (first-line)
Mucormycosis	Liposomal Amphotericin B → Posaconazole/Isavuconazole (step-down)
Candida (ICU/invasive)	Echinocandin (caspofungin, micafungin)
Atypical pneumonia	Macrolide (azithromycin) or Doxycycline or Levofloxacin
Legionella	Levofloxacin or Azithromycin

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
Penicillin allergy and cross-reactivity	Paper I / Paper III	Safety/allergy scenario
Ampicillin rash in EBV	Paper I Medicine	Drug-disease interaction
Flucloxacillin = MSSA only (not MRSA)	Paper I Medicine	Drug selection
Ceftriaxone meningitis/gonorrhoea	Paper I / Paper II	Drug choice scenario
Vancomycin red man syndrome	Paper I / Paper II	Side effect identification
Aminoglycoside ototoxicity (irreversible)	Paper I Medicine	Toxicity/monitoring
Clindamycin → C. difficile (highest risk)	Paper I / Paper II	Drug-complication association
Ciprofloxacin → ↑ theophylline	Paper I Medicine	Drug interaction
Metronidazole + alcohol (disulfiram)	Paper I / Paper II	Drug interaction scenario
Linezolid + SSRIs → serotonin syndrome	Paper I Medicine	Drug interaction
Tetracyclines contraindicated <8 yrs/pregnancy	Paper I / Paper III	Contraindication
Fluconazole does not cover Aspergillus	Paper I Medicine	Coverage trap
Voriconazole = invasive aspergillosis first-line	Paper I Medicine	Drug selection
Amphotericin B nephrotoxicity + infusion reactions	Paper I Medicine	Toxicity management
Echinocandins = IV only, Candida first-line in ICU	Paper I / Paper II	Drug selection

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
Cell wall drugs	PGC = Penicillins, cephalosporins, Glycopeptides, Carbapenems
30S inhibitors	"30 AT" = Aminoglycosides, Tetracyclines
50S inhibitors	"50 MCCL" = Macrolides, Clindamycin, Chloramphenicol, Linezolid
DNA mechanism drugs	"FluoroMet" = Fluoroquinolones (gyrase), Metronidazole (DNA damage)
Vancomycin toxicities	"RED MAN" = Renal (nephro), Ear (oto), Drip-rate reaction (red man)
Aminoglycoside memory	"GET SMART" = Gentamicin, tobramycin - Synergy, Monitoring, Aerobic only, Renal/ear Toxicity
C. difficile culprits	"C's and A's" = Cephalosporins, Clindamycin, Co-amoxiclav, Aminopenicillins, And fluoroquinolones
Antifungal targets	"EEE" = Ergosterol (polyenes), Ergosterol synthesis (azoles), Exoskeleton/cell wall (echinocandins)
Avoid in pregnancy	"FCAT" = Fluoroquinolones, Cotrimoxazole (T1), Aminoglycosides (streptomycin), Tetracyclines

Sources: Lippincott Illustrated Reviews Pharmacology; Sherris & Ryan's Medical Microbiology 8th Edition; Harrison's Principles of Internal Medicine 22E (2025); Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology 16th Edition; Tintinalli's Emergency Medicine.

Give me high-yield HKMLE notes on GI Pharmacology with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - Peptic ulcer drugs (PPIs, H2 blockers, antacids, misoprostol, sucralfate) - Antiemetics (ondansetron, metoclopramide, domperidone, cyclizine, aprepitant) - Antidiarrheals (loperamide, diphenoxylate, bismuth subsalicylate) - Laxatives (bulk-forming, osmotic, stimulant, emollient) - IBD drugs (5-aminosalicylates, steroids, azathioprine, methotrexate, anti-TNF biologics) - Antispasmodics (hyoscine butylbromide, dicyclomine, mebeverine) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Cardio notes.

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

Excellent - I have the IBD safety profiles table from Sleisenger & Fordtran directly. I now have comprehensive data to compile the full GI pharmacology notes.

High-Yield HKMLE: GI Pharmacology Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): PUD management, H. pylori eradication, IBD drug selection, antiemetics, laxatives

Paper II Surgery/Emergency (45 MCQs): Upper GI bleed (PPI use), post-op nausea, bowel prep, C. difficile

Paper III Paediatrics/OG (30 MCQs): Safe antiemetics in pregnancy, IBD drugs in pregnancy, neonatal GI

1. PROTON PUMP INHIBITORS (PPIs)

Mnemonic: "PPIs = Proton Pump Inhibitors → Permanently block acid pumps (irreversible) = Long lasting"

Feature	Detail
Mechanism	Prodrug → activated in acidic environment → irreversibly binds H+/K+-ATPase (proton pump) on gastric parietal cells → ↓ acid secretion (most potent acid suppressant)
Key Indications	Peptic ulcer disease (gastric + duodenal), H. pylori eradication (triple/quadruple therapy), GORD/GERD, Erosive oesophagitis, Stress ulcer prophylaxis (ICU), NSAID-induced ulcer prevention, Zollinger-Ellison syndrome (high-dose), Barrett's oesophagus
Major Side Effects	Generally well tolerated short-term; Long-term: Hypomagnesaemia (most important - monitor with prolonged use), Hyponatraemia, C. difficile infection (↑ risk), Osteoporosis/fractures (↑ with long-term use), Community-acquired pneumonia (↑ risk), Vitamin B12 deficiency, Iron malabsorption, Rebound acid hypersecretion on stopping
Drug Interactions	Omeprazole/esomeprazole inhibit CYP2C19 → ↑ clopidogrel levels reduced (↓ antiplatelet effect - use pantoprazole instead with clopidogrel)
Contraindications	None absolute; avoid unnecessary long-term use
HKMLE Paper	Paper I Medicine, Paper II Surgery

Drug	Notes
Omeprazole	Most widely used; CYP2C19 inhibitor - interacts with clopidogrel
Lansoprazole	Similar to omeprazole
Pantoprazole	Fewest drug interactions → preferred with clopidogrel
Esomeprazole	S-enantiomer of omeprazole; slightly longer action
Rabeprazole	Faster onset; least CYP2C19 interaction

HKMLE Pearls:

PPIs must be taken 30-60 min before meal (proton pumps activated by food → drug works best when pumps active)

PPI + clopidogrel = use pantoprazole (least CYP2C19 inhibition = least reduction of clopidogrel activation)

Long-term PPI → hypomagnesaemia → can cause hypocalcaemia + hypokalaemia (cascading electrolyte effect)

Rebound acid hypersecretion on abrupt PPI discontinuation → taper if long-term use

2. H2 RECEPTOR ANTAGONISTS (H2 Blockers)

Mnemonic: "H2 = Half as good as PPIs but fewer long-term risks"

Feature	Detail
Mechanism	Competitively block histamine H2 receptors on gastric parietal cells → ↓ acid secretion (less potent than PPIs, do not completely suppress acid)
Key Indications	Mild GORD, Peptic ulcer (where PPI not tolerated), Stress ulcer prophylaxis (ranitidine - now less used; famotidine still used), Heartburn, Urticaria (H2 role in skin)
Major Side Effects	Generally well tolerated; Cimetidine = multiple CYP inhibitor + anti-androgenic effects (gynaecomastia, impotence); Headache; Rarely: confusion in elderly/renal failure
HKMLE Paper	Paper I Medicine

Drug	Key Points
Cimetidine	Inhibits CYP1A2, CYP2C9, CYP2D6, CYP3A4 - multiple drug interactions; gynaecomastia (anti-androgenic); first H2 blocker
Ranitidine	Withdrawn in many countries (NDMA contamination); still examined
Famotidine	Safest H2 blocker; fewest drug interactions; used in pregnancy
Nizatidine	Similar to ranitidine

HKMLE Pearl: Cimetidine is the classic exam drug for CYP inhibitor interactions - ↑ warfarin, theophylline, phenytoin, metoprolol. Also causes gynaecomastia (blocks androgen receptors).

3. ANTACIDS

Mnemonic: "ANTACID = Aluminium NeuTrAlises Constipation; mAgnesium = Diarrhoea"

Drug	Type	Side Effects	Key Use
Aluminium hydroxide	Weak base → neutralises HCl	Constipation, Phosphate binding (useful in CKD - binds dietary phosphate), Hypophosphataemia (long-term)	Symptomatic relief; phosphate binder in CKD
Magnesium hydroxide (milk of magnesia)	Weak base	Diarrhoea/laxative effect, Hypermagnesaemia (avoid in renal failure)	Symptomatic relief + mild laxative
Magnesium + Aluminium combo (e.g. Maalox, Gaviscon)	Balanced	Minimal diarrhoea/constipation	Heartburn relief
Sodium bicarbonate	Rapidly neutralises acid	Belching (CO2), Metabolic alkalosis (long-term), Sodium load (avoid in HTN/HF)	Short-term symptomatic; avoid long-term
Calcium carbonate	Neutralises acid	Constipation, Milk-alkali syndrome (hypercalcaemia + alkalosis with excessive use), Rebound acid ↑	Antacid + calcium supplement

HKMLE Pearl: Antacids chelate tetracyclines, quinolones, and iron - do not take within 2 hours of these drugs (↓ absorption).

4. SUCRALFATE

Feature	Detail
Mechanism	Aluminium salt of sucrose octasulfate → polymerises in acidic pH → forms viscous gel → coats ulcer base → physical barrier against acid + pepsin + bile; also ↑ local prostaglandin synthesis
Key Indications	Peptic ulcer (especially duodenal), Stress ulcer prophylaxis (ICU - preferred over PPI in some protocols as less C. difficile risk), NSAID-induced gastropathy
Major Side Effects	Constipation (most common), Aluminium toxicity (accumulation in renal failure)
Interactions	Must be taken on empty stomach; reduces absorption of quinolones, tetracyclines, phenytoin, digoxin (give 2h apart)
Contraindications	Renal failure (aluminium accumulation), Dysphagia
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Sucralfate works only in acidic pH - do NOT co-administer with antacids or PPIs (raises pH, reduces efficacy). Give 1 hour before meals and at bedtime.

5. MISOPROSTOL

Mnemonic: "MISOPROStol = MISery Prevention (NSAID ulcers) + MISCARRIAGE (uterine contractions = contraindicated in pregnancy unless inducing)"

Feature	Detail
Mechanism	Synthetic PGE1 prostaglandin analogue → ↑ mucus + bicarbonate secretion (cytoprotection), ↓ acid secretion (inhibits parietal cell cAMP), ↑ mucosal blood flow
Key Indications	Prevention of NSAID-induced gastric ulcers (patients at high risk who cannot stop NSAIDs), Medical termination of pregnancy (with mifepristone), Cervical ripening, Postpartum haemorrhage
Major Side Effects	Diarrhoea (most common, dose-dependent), Abdominal cramping, Uterine contractions (→ avoid in pregnancy unless intended)
Contraindications	Pregnancy (causes uterine contractions/abortion) - unless being used for termination; breastfeeding
HKMLE Paper	Paper I Medicine, Paper II Surgery, Paper III OG

HKMLE Pearl: PPIs are now preferred over misoprostol for NSAID ulcer prevention (better tolerated). Misoprostol = cytoprotective BUT causes diarrhoea + uterine contractions.

6. H. PYLORI ERADICATION REGIMENS

Mnemonic: "PAC = PPI + Amoxicillin + Clarithromycin (Triple therapy)" or "PCAM = Quadruple"

Standard Regimens

Regimen	Drugs	Duration	Use
Standard Triple Therapy	PPI + Amoxicillin + Clarithromycin	7-14 days	First-line (if clarithromycin resistance <15%)
Bismuth Quadruple	PPI + Bismuth + Metronidazole + Tetracycline	10-14 days	First-line in high clarithromycin resistance areas; second-line after triple failure
Levofloxacin Triple	PPI + Amoxicillin + Levofloxacin	10-14 days	Third-line/salvage
Penicillin allergy	PPI + Clarithromycin + Metronidazole	7-14 days	Alternative if amoxicillin allergy

HKMLE Pearls:

Test for eradication: urea breath test or stool antigen test at least 4 weeks after completing therapy (not serology - antibodies persist)

Serology (H. pylori IgG) cannot confirm eradication (remains positive years after)

PPIs are part of ALL regimens (acid suppression improves antibiotic efficacy)

Bismuth has direct antimicrobial + cytoprotective effect; turns stools black (warn patient)

7. ANTIEMETICS

7a. 5-HT3 Antagonists

Mnemonic: "Setrons = Stop vomiting (chemo/surgery), QT prolongation (5HTs are 3 serotonin setrons)"

Feature	Detail
Mechanism	Block 5-HT3 (serotonin) receptors in GI tract and CNS (chemo-trigger zone + vagal afferents) → ↓ nausea and vomiting
Key Indications	Chemotherapy-induced nausea/vomiting (CINV - first-line), Post-operative nausea/vomiting (PONV), Radiotherapy-induced nausea
Major Side Effects	QT prolongation (especially ondansetron IV - dose limit 32mg IV), Headache, Constipation, Transient ↑ LFTs
Contraindications	Congenital long QT, Concurrent QT-prolonging drugs; ondansetron IV max 16mg single dose (UK guideline change after cardiac risk found)
HKMLE Paper	Paper I Medicine, Paper II Surgery

Key drugs: Ondansetron (most common), Granisetron, Palonosetron (longest t½ - best for delayed CINV)

HKMLE Pearls:

Ondansetron 4mg IV = standard for PONV

Do NOT give IV ondansetron as rapid bolus (arrhythmia risk) - give over 15-30 min or diluted

Serotonin syndrome risk if combined with other serotonergic drugs

7b. Dopamine Antagonists (Prokinetics)

Mnemonic: "MET + DOM block Dopamine → Move gut forward + stop vomit - but MET causes EPS"

Feature	Metoclopramide	Domperidone
Mechanism	D2 antagonist + 5-HT3 antagonist + 5-HT4 agonist → prokinetic + antiemetic	D2 antagonist (peripheral > central, does not cross BBB well) → antiemetic + prokinetic
Key Indications	PONV, Chemotherapy nausea, Gastroparesis (diabetic), GORD, Hiccups	Nausea/vomiting, Gastroparesis, Prokinetic for nausea
Major Side Effects	Extrapyramidal effects (acute dystonia, tardive dyskinesia with long-term use), Drowsiness, Hyperprolactinaemia (galactorrhoea), Tardive dyskinesia (irreversible with prolonged use)	QT prolongation (cardiac risk - restricted use), Hyperprolactinaemia; Less EPS (does not cross BBB well)
Contraindications	GI obstruction, Phaeochromocytoma (↑ catecholamine release), Parkinson's disease, History of tardive dyskinesia	QT prolongation, Severe hepatic impairment, Concurrent QT drugs; restricted in many countries
HKMLE Paper	Paper I Medicine, Paper III OG

HKMLE Pearls:

Metoclopramide EPS → treat acute dystonia with IM procyclidine or benztropine (anticholinergic)

Domperidone safe in pregnancy (limited data but more used); metoclopramide also used

Long-term metoclopramide → tardive dyskinesia (irreversible) - limit use to <3 months

Erythromycin (macrolide) is also a prokinetic via motilin receptor agonism (used in gastroparesis/ICU gastric emptying)

7c. Antihistamine Antiemetics

Mnemonic: "CYCLIZINE = Cycle sickness, children, sedating"

Drug	Mechanism	Key Use	Side Effects
Cyclizine	H1 + muscarinic antagonist	Motion sickness, PONV, Vestibular causes of nausea, Pregnancy nausea (1st trimester)	Sedation, Dry mouth, Urinary retention
Promethazine	H1 + D2 + muscarinic antagonist	Motion sickness, Pregnancy nausea	Sedation, EPS (rare), Extrapyramidal in children
Cinnarizine	H1 + Ca2+ channel blocker	Motion sickness, Vestibular disorders	Sedation, Extrapyramidal effects

HKMLE Pearl: Cyclizine = safe in pregnancy (1st trimester), preferred over metoclopramide for early pregnancy nausea.

7d. NK1 Receptor Antagonists

Feature	Detail
Drug	Aprepitant (oral), Fosaprepitant (IV prodrug)
Mechanism	Block substance P at NK1 receptors in CNS → prevents delayed CINV
Key Indications	Prevention of delayed CINV (given with 5-HT3 antagonist + dexamethasone = "triple therapy" for highly emetogenic chemotherapy)
Side Effects	Hiccups, Fatigue, Constipation; CYP3A4 inhibitor → ↑ dexamethasone levels (reduce dex dose)
HKMLE Paper	Paper I Medicine

7e. Others

Drug	Mechanism	Use	Note
Dexamethasone	Unknown antiemetic mechanism	PONV prophylaxis, CINV (part of triple therapy)	Potentiates 5-HT3 antagonists
Hyoscine (Scopolamine)	Anticholinergic	Motion sickness (transdermal patch behind ear)	Dry mouth, blurred vision, sedation
Nabilone/Dronabinol	CB1 cannabinoid agonist	Refractory CINV	Euphoria, dizziness; controlled substance

8. ANTIDIARRHOEALS

8a. Opioid-Based

Mnemonic: "LOPE = LOng Poo Eliminator → but don't use in infection (prolongs it)"

Drug	Mechanism	Key Use	Side Effects	Contraindications
Loperamide	μ-opioid receptor agonist in gut wall → ↓ peristalsis, ↑ anal tone, ↓ secretion; does NOT cross BBB (no CNS effects)	Acute non-infective diarrhoea, IBS-D, Ileostomy output control	Constipation, Abdominal cramping, Toxic megacolon (if used in infective diarrhoea)	Infective diarrhoea (invasive bacteria - C. difficile, Salmonella, E. coli O157 - can worsen/prolong infection/cause toxic megacolon), Bloody diarrhoea, Children <2 yrs
Codeine phosphate	μ-opioid receptor agonist (systemic)	Severe diarrhoea (short-term)	Constipation, CNS effects, Dependence	Same as above; avoid in infective diarrhoea

HKMLE Pearls:

Loperamide = safe in traveller's diarrhoea (mild/watery, no blood/fever)

NEVER use loperamide in bloody diarrhoea or suspected C. difficile

Loperamide overdose (high doses) → cardiac arrhythmia + QT prolongation (black box warning in US)

8b. Bismuth Subsalicylate (Pepto-Bismol)

Feature	Detail
Mechanism	Antimicrobial (bismuth toxicity to bacteria), antacid, anti-inflammatory (salicylate component)
Key Indications	Traveller's diarrhoea (prevention + treatment), H. pylori (quadruple therapy), Nausea
Major Side Effects	Black stools (bismuth sulfide - warn patient, not GI bleed!), Black tongue, Tinnitus (salicylate - at high doses), Constipation
Contraindications	Aspirin allergy (salicylate content), Children with viral illness (Reye's syndrome risk), Pregnancy
HKMLE Paper	Paper I Medicine

9. LAXATIVES

Mnemonic: "BOSS" = Bulk, Osmotic, Stimulant, Stool Softeners

Laxative Classification Table

Class	Drugs	Mechanism	Side Effects	Key Use
Bulk-forming	Ispaghula husk (psyllium), Methylcellulose	Absorb water → ↑ stool bulk + soften → stimulates peristalsis	Flatulence, Bloating; must take with plenty of water (intestinal obstruction if inadequate fluid!)	IBS-C, Mild constipation, Diverticular disease
Osmotic	Lactulose, Macrogol (PEG), Magnesium hydroxide (milk of magnesia), Sodium phosphate	Draw water into bowel lumen by osmosis	Bloating, flatulence (lactulose); Electrolyte disturbance (sodium/magnesium overload in renal failure); Taste issues	Constipation, Lactulose → hepatic encephalopathy (↓ NH3), Bowel prep (PEG + electrolytes)
Stimulant	Senna, Bisacodyl, Sodium picosulfate, Castor oil	Stimulate enteric nerve plexus → ↑ colonic motility; also ↓ water/electrolyte absorption	Abdominal cramping, Hypokalaemia (with chronic use), Melanosis coli (anthraquinones/senna = brown pigmentation, benign), Abdominal pain	Opioid-induced constipation (first choice!), Hospital constipation, Before procedures
Stool softeners (Emollient)	Docusate sodium, Arachis oil enema	Surfactant → ↓ surface tension → soften and lubricate stool	Minimal; GI irritation	Mild constipation, Elderly, Post-operative
Rectal	Glycerol suppository, Phosphate enema	Local rectal stimulation / osmotic flush	Local irritation	Quick relief, Faecal impaction
Secretagogues	Linaclotide, Lubiprostone	↑ intestinal Cl- secretion → ↑ fluid in gut lumen	Diarrhoea	IBS-C, Chronic idiopathic constipation

HKMLE Pearls:

Lactulose = osmotic laxative; also used in hepatic encephalopathy (↓ ammonia production by gut bacteria by ↓ pH + trap NH4+)

Senna/bisacodyl = first choice for opioid-induced constipation (stimulant laxative, not bulking)

PEG (macrogol) = bowel prep for colonoscopy, safe in renal failure (balanced electrolytes)

Bulk-forming agents need adequate fluid intake (risk of oesophageal/intestinal obstruction without sufficient water)

Chronic stimulant laxative use → melanosis coli (harmless pigmentation, exam question)

10. IBD DRUGS

Step-Up Approach

Disease	Mild	Moderate	Severe	Maintenance
UC	5-ASA (oral + rectal)	Oral steroids	IV steroids ± Ciclosporin/Infliximab (rescue)	5-ASA ± Azathioprine
Crohn's	5-ASA (less effective), Budesonide	Oral prednisolone	IV steroids ± Anti-TNF (infliximab)	Azathioprine/6-MP ± Anti-TNF

10a. 5-Aminosalicylates (5-ASA)

Mnemonic: "5-ASA = 5 letters = Affects mucosal inflammation locally"

Feature	Detail
Mechanism	Anti-inflammatory at colonic mucosa: inhibit NF-κB + arachidonic acid pathways → ↓ prostaglandins, ↓ leukotriene B4, ↓ cytokines; unclear if purely local or systemic
Key Indications	Ulcerative colitis (induction + maintenance; cornerstone of UC treatment), Mild-moderate Crohn's (limited evidence; mainly colonic)
Major Side Effects	GI (nausea, diarrhoea, cramping), Headache, Rash; Sulfasalazine-specific: Folate deficiency (supplement folic acid), Reversible male infertility (oligospermia), Haemolysis (G6PD deficiency), Agranulocytosis (rare); Rare class effects: Pancreatitis, Interstitial nephritis (monitor renal function!), Paradoxical disease flare
Contraindications	Aspirin/salicylate allergy (mesalazine); G6PD deficiency (sulfasalazine - haemolysis)
HKMLE Paper	Paper I Medicine

Drug	Notes
Mesalazine (5-ASA)	Available as oral tablets (coated for colonic release), enemas, suppositories
Sulfasalazine	5-ASA linked to sulfapyridine; male infertility (oligospermia) - switched to mesalazine if planning paternity; must supplement folic acid
Balsalazide, Olsalazine	Prodrugs of 5-ASA; colonic release; olsalazine → secretory diarrhoea

HKMLE Pearl: Sulfasalazine = male infertility (reversible) + folic acid needed. Switch to sulfa-free mesalazine if planning fatherhood. 5-ASA reduces colorectal cancer risk in UC (long-term benefit).

10b. Corticosteroids in IBD

Drug	Use	Advantage	Key SE
Prednisolone (oral)	Induction of remission (moderate flare)	Effective; well known	Full systemic steroid SEs (see Endocrine notes)
Hydrocortisone (IV)	Severe UC/Crohn flare	Fast-acting	Full systemic SEs
Budesonide (oral)	Mild-moderate Crohn's (especially ileocaecal), Microscopic colitis	First-pass hepatic metabolism → ↓ systemic SEs; fewer side effects than prednisolone	Less systemic absorption; still some adrenal suppression at 9mg/day

HKMLE Pearl: Budesonide = local action steroid for ileocaecal Crohn's; preferred when wanting fewer systemic steroid side effects. Does NOT work as well for extensive colitis.

10c. Immunomodulators

Mnemonic: "AZA = AZA waits 3 months before working = TPMT test first"

Drug	Mechanism	Use	Key Side Effects	Key Points
Azathioprine (AZA)	Prodrug → 6-mercaptopurine (6-MP) → inhibit purine synthesis → ↓ lymphocyte proliferation	Maintenance of remission (UC + Crohn's), Steroid-sparing	Myelosuppression (↑ infection risk), Pancreatitis (up to 5%, early - any dose), Hepatotoxicity, Nausea, Lymphoma risk (long-term), Opportunistic infections	Check TPMT enzyme activity before starting (low TPMT = ↑ toxicity); monitor FBC monthly; takes 3 months for full effect; avoid live vaccines
6-Mercaptopurine (6-MP)	Active metabolite of azathioprine	Similar to AZA	Similar	Same monitoring as AZA
Methotrexate (MTX)	Inhibit dihydrofolate reductase → ↓ purine/pyrimidine synthesis → anti-inflammatory	Crohn's maintenance (especially after steroid dependence); second-line UC	Hepatotoxicity (avoid alcohol, monitor LFTs), Teratogen (Category X - MUST use contraception), Myelosuppression, Pulmonary toxicity	Give folic acid 5mg once weekly (different day to MTX) to reduce toxicity; MUST stop 3 months before conception
Ciclosporin (Cyclosporine)	Calcineurin inhibitor → ↓ IL-2 → ↓ T-cell activation	Severe acute UC (IV rescue therapy before colectomy)	Nephrotoxicity, Hypertension, Neurotoxicity, Hirsutism, Gingival hyperplasia	Bridge to azathioprine; not for long-term UC maintenance
Tacrolimus	Calcineurin inhibitor (more potent than ciclosporin)	Refractory UC (off-label)	Similar to ciclosporin but more nephrotoxic; diabetogenic	Not standard first-line

HKMLE Pearls:

TPMT test = thiopurine methyltransferase activity before azathioprine/6-MP; low activity → ↑ toxic metabolites → severe myelosuppression → start lower dose

Pancreatitis with AZA = dose-independent, occurs early → stop drug permanently (re-challenge risky)

Methotrexate = teratogen → never give to pregnant women without counselling + contraception

10d. Biological Therapies

Mnemonic: "FIAT = Full range: anti-TNF (Infliximab, Adalimumab), anti-Integrin (vedolizumab), anti-IL (ustekinumab)"

Drug	Class	Mechanism	Indication	Key Side Effects
Infliximab	Anti-TNFα (chimeric monoclonal Ab)	Binds TNFα → prevents binding to TNF receptors → ↓ inflammation	Moderate-severe UC and Crohn's (induction + maintenance); Fistulising Crohn's	TB reactivation (screen with IGRA/CXR before!), Opportunistic infections, Infusion reactions, Drug-induced lupus, Demyelination, Worsening heart failure, Lymphoma
Adalimumab	Anti-TNFα (fully human Ab)	Same as infliximab	Moderate-severe UC and Crohn's; SC injection (patient self-administered)	Similar to infliximab; injection site reactions; fewer infusion reactions
Golimumab	Anti-TNFα	Similar	Moderate-severe UC	Similar to above
Certolizumab	Anti-TNFα (PEGylated Fab fragment)	Does NOT cross placenta fully	Crohn's; safest anti-TNF in pregnancy	Similar class effects
Vedolizumab	Anti-integrin (anti-α4β7)	Blocks α4β7 integrin → prevents lymphocyte migration into gut mucosa → gut-selective	Moderate-severe UC and Crohn's (especially after anti-TNF failure)	Gut-selective → fewer systemic infections; nasopharyngitis; headache; less TB risk than anti-TNF
Ustekinumab	Anti-IL-12/23 (anti-p40 subunit)	Block Th1/Th17 pathways	Moderate-severe Crohn's (and UC)	Injection site reactions, Nasopharyngitis; less infection risk than anti-TNF

HKMLE Pearls:

Screen for TB (IGRA or Mantoux + CXR) before ALL anti-TNF biologics - highest priority screening

Heart failure is a contraindication for anti-TNF (infliximab/adalimumab worsen HF)

Vedolizumab = gut-selective → preferred if systemic infection concern or prior TB

Infliximab = IV infusion (3 doses induction: 0, 2, 6 weeks); adalimumab = SC fortnightly

All biologics = avoid live vaccines (yellow fever, BCG, MMR, varicella)

11. ANTISPASMODICS

Mnemonic: "ANTISPASM = Anticholinergics = Atropine-like symptoms"

Drug	Mechanism	Key Use	Side Effects	Key Points
Hyoscine butylbromide (Buscopan)	Antimuscarinic → ↓ GI smooth muscle spasm; quaternary ammonium - does NOT cross BBB	Abdominal/colicky pain (IBS, renal colic, biliary colic, bowel spasm), Irritable bowel syndrome	Dry mouth, Urinary retention, Constipation, Tachycardia; No CNS side effects (quaternary compound = doesn't cross BBB)	Widely used, safe, quick IV/IM action; IV for acute spasm (e.g. endoscopy, renal colic)
Dicyclomine	Antimuscarinic + direct smooth muscle relaxant	IBS	Dry mouth, Urinary retention, Drowsiness, Tachycardia	Crosses BBB somewhat; avoid in infants (<6 months, apnea reported)
Mebeverine	Direct smooth muscle relaxant (Ca2+ channel effect) - not anticholinergic	IBS (preferred if anticholinergic SEs problematic)	GI upset; No anticholinergic side effects (unlike hyoscine/dicyclomine)	Preferred in elderly/glaucoma/BPH where anticholinergics contraindicated
Peppermint oil	Direct smooth muscle relaxation (blocks Ca2+ channels)	IBS (mild)	Heartburn, Perianal burning; enteric-coated to prevent GORD	OTC; safe; limited evidence
Alverine citrate	Direct smooth muscle relaxant	IBS	GI side effects	Similar to mebeverine

HKMLE Pearls:

Hyoscine butylbromide (Buscopan) = most commonly tested; quaternary ammonium → no CNS effects

Contraindications for anticholinergics: narrow-angle glaucoma, BPH, myasthenia gravis, paralytic ileus

Mebeverine = no anticholinergic SEs → safe alternative in elderly with glaucoma or prostate issues

12. H. PYLORI - EXAM SUMMARY

Test	Accuracy	Notes
Urea breath test (UBT)	High (95%+)	Best non-invasive test; confirm eradication (4 weeks post-treatment, off PPI for 2 weeks)
Stool antigen test	High	Alternative to UBT for eradication check
Serology (IgG)	Moderate	Cannot confirm eradication (antibodies persist); use for initial diagnosis only
Rapid urease test (CLO test)	High (invasive)	On endoscopic biopsy; rapid bedside result
Histology	Gold standard (invasive)	Endoscopic biopsy

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
PPI mechanism + long-term SEs (hypoMg, C. diff)	Paper I Medicine	Side effect identification
PPI + clopidogrel interaction (use pantoprazole)	Paper I Medicine	Drug interaction
Cimetidine = CYP inhibitor + gynaecomastia	Paper I Medicine	Drug interaction / side effect
H. pylori eradication regimen (PAC)	Paper I Medicine	Management protocol
H. pylori eradication testing (UBT not serology)	Paper I Medicine	Monitoring/testing
Misoprostol = contraindicated in pregnancy	Paper I / Paper III OG	Contraindication scenario
Sucralfate administration (empty stomach, not with PPI)	Paper I Medicine	Administration rule
Ondansetron QT prolongation	Paper I / Paper II	Side effect / monitoring
Metoclopramide EPS → procyclidine treatment	Paper I / Paper II	Complication management
Loperamide contraindicated in infective/bloody diarrhoea	Paper I / Paper II	Contraindication MCQ
Lactulose in hepatic encephalopathy	Paper I Medicine	Mechanism/indication
Senna = opioid-induced constipation first choice	Paper I Medicine	Drug selection
TPMT test before azathioprine (IBD)	Paper I Medicine	Monitoring protocol
TB screening before anti-TNF	Paper I Medicine	Pre-treatment screening
Methotrexate = teratogen + folic acid supplementation	Paper I / Paper III	Contraindication/monitoring
Sulfasalazine = male infertility + folic acid	Paper I Medicine	Side effect identification
Vedolizumab = gut-selective (less TB risk)	Paper I Medicine	Drug selection/mechanism

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
PPI long-term SEs	"PPI CHOB" = C. difficile, Hypomagnesaemia, Osteoporosis, B12 deficiency
H. pylori triple therapy	PAC = PPI + Amoxicillin + Clarithromycin
H. pylori quadruple therapy	PBMT = PPI + Bismuth + Metronidazole + Tetracycline
Antiemetics by receptor	"5-HT3 Setrons, D2 MET/DOM, H1 Cyclizine, NK1 Aprepitant"
Laxative types	BOSS = Bulk, Osmotic, Stimulant, Softeners
Opioid constipation laxative	Senna first (stimulant) not bulk-forming
AZA before starting	TPMT test → 3 months to work → monitor FBC monthly
Anti-TNF screening	TITS = Tuberculosis (IGRA), Infections screen, Trophoblastic (pregnancy test), Stress test heart (no HF)
Mebeverine vs hyoscine	Mebeverine = No Muscarinic side effects

Sources: Sleisenger and Fordtran's Gastrointestinal and Liver Disease; Yamada's Textbook of Gastroenterology 7th Edition; Lippincott Illustrated Reviews Pharmacology; Harrison's Principles of Internal Medicine 22E (2025); Katzung's Basic and Clinical Pharmacology 16th Edition; Swanson's Family Medicine Review.

Give me high-yield HKMLE notes on Rheumatology Pharmacology with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - NSAIDs (non-selective: ibuprofen, diclofenac, naproxen, indomethacin; COX-2 selective: celecoxib, etoricoxib) - Simple analgesics (paracetamol/acetaminophen) - Corticosteroids in rheumatology (intra-articular, oral, IV pulse) - Conventional DMARDs (methotrexate, sulfasalazine, hydroxychloroquine, leflunomide) - Biologic DMARDs (TNF inhibitors: infliximab, adalimumab, etanercept; IL-6 inhibitor: tocilizumab; IL-1 inhibitor: anakinra; rituximab anti-CD20; abatacept) - Gout drugs (colchicine, allopurinol, febuxostat, probenecid, pegloticase) - Osteoarthritis drugs (topical NSAIDs, oral NSAIDs, duloxetine, intra-articular hyaluronic acid) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Antibiotics notes.

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

I now have comprehensive data from Lippincott and Katzung's across all rheumatology pharmacology topics. Let me compile the complete notes.

High-Yield HKMLE: Rheumatology Pharmacology Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): RA/SLE/gout/OA drugs, DMARD monitoring, drug interactions, gout management

Paper II Surgery/Emergency (45 MCQs): Perioperative NSAID/DMARD management, acute gout, septic arthritis

Paper III Paediatrics/OG (30 MCQs): DMARDs in pregnancy (MTX contraindication), JIA drugs, NSAIDs in pregnancy

MASTER OVERVIEW: Drug Categories in Rheumatology

Mnemonic: "PAIN STOPS BETTER with BDAM"

Analgesics: Paracetamol, Opioids
Anti-inflammatories: NSAIDs (non-selective + COX-2 selective)
Steroids (corticosteroids: local/systemic)
DMARDs (conventional: MTX, SSZ, HCQ, LEF)
Biologics (anti-TNF, anti-IL-6, anti-CD20, anti-CTLA4)
Anti-gout (colchicine, allopurinol, febuxostat, probenecid)
Miscellaneous (JAK inhibitors)

1. PARACETAMOL (Acetaminophen)

Mnemonic: "PARA = Pain + Afebrile = no Antiplatelet effect = safe in stomach + pregnancy"

Feature	Detail
Mechanism	Inhibits prostaglandin synthesis in CNS only (not peripheral tissues → weak anti-inflammatory); exact mechanism unclear (possible COX-3 inhibition); does NOT affect platelets
Key Indications	Mild-moderate pain (first-line analgesic for OA, musculoskeletal pain), Fever, Safe alternative to NSAIDs in GI/renal/CV risk patients
Major Side Effects	Generally very safe at therapeutic doses; HEPATOTOXICITY in overdose (via toxic metabolite NAPQI - depletes hepatic glutathione)
Contraindications	Severe hepatic impairment, Chronic heavy alcohol use (depletes glutathione → ↑ NAPQI toxicity), G6PD deficiency
HKMLE Paper	Paper I Medicine, Paper II, Paper III

Paracetamol Overdose - HIGH YIELD

Feature	Detail
Toxic metabolite	NAPQI (N-acetyl-p-benzoquinoneimine) accumulates when glutathione depleted
Clinical phases	Phase 1 (0-24h): N/V, malaise; Phase 2 (24-72h): RUQ pain, ↑ LFTs; Phase 3 (72-96h): Hepatic failure, jaundice, coagulopathy, renal failure
Treatment	N-acetylcysteine (NAC) IV - replenishes glutathione; start immediately (most effective <8-10h, still give even late); treat to Rumack-Matthew nomogram
Other	Activated charcoal if <1h post-ingestion; liver transplant assessment if massive ingestion

HKMLE Pearls:

Paracetamol does NOT inhibit platelets - safe pre/post-surgery

Safe in all trimesters of pregnancy (unlike NSAIDs)

Staggered overdose (multiple smaller doses over time) is more dangerous than single OD

Risk factors for NAPQI toxicity: alcoholism, malnutrition, enzyme inducers (rifampicin, phenytoin, carbamazepine)

2. NSAIDs (Non-Selective COX Inhibitors)

Mnemonic: "NSAIDs = No Safe choice for: Stomach (GI bleed), Salt (renal/HTN), Second trimester/baby (closes PDA), Surgeries (bleeding), Sulfonamide allergy (celecoxib)"

Feature	Detail
Mechanism	Non-selectively inhibit COX-1 and COX-2 → ↓ prostaglandin and thromboxane synthesis → analgesic, anti-inflammatory, antipyretic, antiplatelet effects
COX-1 effects	Constitutive enzyme: gastric cytoprotection (PGE2/PGI2 → mucus + bicarb), platelet aggregation (TXA2), renal perfusion
COX-2 effects	Inducible (inflammatory): fever, pain, inflammation; also some renal and vascular function

NSAID Class Side Effects (Apply to ALL Non-Selective NSAIDs)

System	Side Effects
GI	Peptic ulcer, GI bleed, perforation (↓ mucosal protection via ↓ PGE2); worst with indomethacin and piroxicam
Renal	Acute renal failure (↓ renal prostaglandins → ↓ GFR), Fluid retention, Hyperkalaemia, Hypertension, Papillary necrosis (chronic)
Cardiovascular	↑ risk of MI, stroke, HF (even short-term) - class effect; worst with COX-2 inhibitors and diclofenac
Haematological	Inhibit platelet aggregation (reversible, except aspirin = irreversible) → ↑ bleeding time
Pulmonary	Aspirin-exacerbated respiratory disease (AERD/Samter's triad): asthma + nasal polyps + aspirin sensitivity → bronchoconstriction
Pregnancy	Premature closure of ductus arteriosus (T3) → avoid in T3; oligohydramnios; T1 use linked to miscarriage
CNS	Indomethacin: severe headache, dizziness (most CNS-toxic NSAID)
Skin	Photosensitivity (naproxen, piroxicam); Stevens-Johnson syndrome (rare)

Individual NSAID Comparison

Drug	Key Features	HKMLE-Specific Use
Ibuprofen	Lowest CV risk of non-selective NSAIDs; lowest GI risk; OTC; short t½	OA, RA, Dysmenorrhoea, Mild pain
Naproxen	Lowest CV risk (best cardiovascular safety profile in class); twice daily	OA, RA, Acute gout, Migraine
Diclofenac	Higher CV risk (similar to COX-2); moderate GI risk; topical = less systemic	OA (topical first-line in elderly), RA, Dental pain
Indomethacin	Most potent NSAID; classic for acute gout; closes PDA (used medically to close patent ductus arteriosus in neonates)	Acute gout, Ankylosing spondylitis, PDA closure
Aspirin (high dose)	Anti-inflammatory at >2g/day; antiplatelet at 75-150mg/day; NEVER in children <12 (Reye's syndrome)	Anti-inflammatory (historically), Kawasaki disease (+ IVIG)
Ketorolac	Potent; only NSAID available IV/IM (used for post-op pain)	Short-term post-op analgesia
Piroxicam	Long t½ (once daily); high GI bleeding risk	Limited use; avoided in elderly

Contraindications (All NSAIDs)

Contraindication	Reason
Active PUD / GI bleed	↓ mucosal protection
Severe renal impairment (eGFR <30)	Acute kidney injury risk
Severe HF / decompensated liver disease	Fluid retention, renal failure
3rd trimester pregnancy	Premature closure of PDA, oligohydramnios
Aspirin-exacerbated asthma (AERD)	Bronchoconstriction (all NSAIDs cross-react)
Concurrent anticoagulation (relative)	↑ bleeding risk

HKMLE Pearl: Indomethacin = NSAID used to close patent ductus arteriosus in premature neonates (inhibits prostaglandin E2 that keeps PDA open). The same mechanism causes PDA closure as a side effect in 3rd trimester - thus contraindicated in late pregnancy.

3. COX-2 SELECTIVE INHIBITORS (Coxibs)

Mnemonic: "COX-2 = protects GI but COX-2 blocks PGI2 (prostacyclin) → Cardiovascular clot risk"

Feature	Detail
Mechanism	Selectively inhibit COX-2 only → ↓ inflammation without inhibiting COX-1 → preserves gastric mucosa and platelet function; but ↓ PGI2 (vasodilatory/antiplatelet prostacyclin) → ↑ CV thrombotic risk
Key Indications	OA, RA in patients at high GI risk (elderly, prior ulcer, on anticoagulants); dysmenorrhoea; acute pain
Major Side Effects	↑ Cardiovascular risk (MI, stroke - class effect; highest with rofecoxib = withdrawn); Renal side effects = same as non-selective NSAIDs; Sulfonamide allergy = celecoxib contraindicated (contains sulfonamide moiety)
Advantage over NSAIDs	↓ GI ulcers/bleeding (but benefit lost if concurrent low-dose aspirin given)
Contraindications	Established cardiovascular disease (use with caution), Sulfonamide allergy (celecoxib), Severe renal/hepatic impairment, Pregnancy (same as NSAIDs)
HKMLE Paper	Paper I Medicine

Key drugs: Celecoxib (most common in practice), Etoricoxib

HKMLE Pearls:

Rofecoxib (Vioxx) was withdrawn in 2004 due to ↑ MI risk (seminal pharmacovigilance example)

COX-2 inhibitors do NOT inhibit platelet aggregation → do NOT replace antiplatelet therapy

Celecoxib + aspirin = GI benefit disappears (aspirin itself causes GI irritation via COX-1)

Celecoxib contains a sulfonamide group → avoid in sulfa allergy

4. CONVENTIONAL DMARDs

4a. Methotrexate (MTX)

Mnemonic: "MTX = Must Take X-amount (folic acid), Must Test Xrays + LFTs monthly, Must eXclude pregnancy"

Feature	Detail
Mechanism	Inhibits dihydrofolate reductase (DHFR) → ↓ tetrahydrofolate → ↓ purine/pyrimidine synthesis → ↓ rapidly dividing cells (lymphocytes) → anti-inflammatory; also ↑ adenosine release → anti-inflammatory
Key Indications	First-line conventional DMARD for RA (anchor drug), Psoriatic arthritis, Psoriasis, Juvenile idiopathic arthritis (JIA), SLE (refractory skin/joint), IBD (Crohn's), Ectopic pregnancy (high dose), Choriocarcinoma
Major Side Effects	Hepatotoxicity (↑ ALT; fibrosis with long-term use; avoid alcohol), Pulmonary toxicity (MTX pneumonitis - acute/subacute dyspnoea, fever, hypoxia; can be fatal), Myelosuppression (leucopenia, thrombocytopaenia), Mouth ulcers/mucositis, Nausea/GI upset, Teratogen (Category X), Renal impairment → drug accumulation → toxicity
Monitoring	FBC + LFTs at baseline, then monthly (first 3-6 months), then 3-monthly; CXR at baseline; Renal function
Prevention of toxicity	Folic acid 5mg once weekly (different day to MTX) - reduces GI side effects and mucositis without reducing efficacy
Contraindications	Pregnancy (must use contraception; stop 3 months before conception - men AND women), Breastfeeding, Significant hepatic disease, Significant renal impairment (eGFR <30), Active serious infection, Immunodeficiency, Alcoholism
Drug interactions	NSAIDs ↑ MTX toxicity (↓ renal clearance - avoid NSAIDs in patients on high-dose MTX); Trimethoprim/co-trimoxazole (folate antagonism → severe toxicity); Probenecid ↑ MTX levels
HKMLE Paper	Paper I Medicine, Paper III OG

HKMLE Pearls:

MTX pneumonitis = new dry cough + dyspnoea + fever in patient on MTX → stop MTX immediately; can occur at any time; chest CT shows interstitial infiltrates

Folic acid 5mg once weekly = must always be co-prescribed (exam: if patient on MTX gets mucositis/nausea = ↑ folic acid dose)

MTX once weekly in RA (NOT daily - much higher toxicity daily)

Leucovorin (folinic acid) = rescue for MTX toxicity/overdose

4b. Sulfasalazine (SSZ)

Mnemonic: "SSZ = Sperm Stops (male infertility), Skin rash (sulfa), Slow onset (3 months)"

Feature	Detail
Mechanism	Cleaved in colon to sulfapyridine (antibacterial) + 5-aminosalicylate (anti-inflammatory); inhibits prostaglandins and cytokines
Key Indications	RA (first-line DMARD), Psoriatic arthritis, Ankylosing spondylitis (peripheral joints), Ulcerative colitis, Crohn's colitis
Major Side Effects	GI (nausea, vomiting, diarrhoea), Reversible male infertility (oligospermia - switch to mesalazine), Folate deficiency (supplement folic acid), Rash, Haemolysis (G6PD deficiency), Agranulocytosis (rare), Orange-yellow discolouration of urine/skin/lenses
Contraindications	Sulfonamide allergy, G6PD deficiency, Severe renal/hepatic impairment, Porphyria
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Generally safe in pregnancy (preferred over MTX/LEF). Male infertility = reversible - switch to mesalazine if planning fatherhood. Orange urine = harmless (warn patient).

4c. Hydroxychloroquine (HCQ)

Mnemonic: "HCQ = Happy drug (safe), Hydroxychloroquine CHecks Q = (retina must be checked Quinquennially = 5-yearly)"

Feature	Detail
Mechanism	Accumulates in lysosomes → ↑ pH → inhibits antigen processing/presentation + TLR7/9 signalling → ↓ autoimmune inflammation
Key Indications	SLE (reduces flares, prevents organ damage, safe in lupus pregnancy), Discoid lupus, RA (mild disease; steroid-sparing), Sjögren's syndrome, Anti-phospholipid antibody syndrome (adjunct), Malaria prophylaxis/treatment
Major Side Effects	Generally very safe; Retinopathy/maculopathy (cumulative dose-dependent; "bull's-eye maculopathy" → irreversible vision loss), GI upset, Skin hyperpigmentation, Cardiomyopathy (rare)
Monitoring	Annual ophthalmology review after 5 years of use (or sooner if risk factors: renal impairment, high dose, baseline retinal disease)
Contraindications	Pre-existing maculopathy/retinopathy, G6PD deficiency
HKMLE Paper	Paper I Medicine, Paper III OG

HKMLE Pearls:

Safest DMARD in pregnancy → continue throughout pregnancy in SLE (reduces neonatal lupus and flares)

Retinopathy is irreversible → monitor with annual ophthalmic screening including visual field testing + OCT

HCQ may prolong QT interval → caution with other QT-prolonging drugs

4d. Leflunomide (LEF)

Mnemonic: "LEFlunomide = LEFt the pregnancy behind (teratogen), LiFts up blood pressure, LiFts LFTs"

Feature	Detail
Mechanism	Inhibits dihydroorotate dehydrogenase (DHODH) → ↓ pyrimidine synthesis → ↓ T and B lymphocyte proliferation
Key Indications	RA (first-line DMARD, used when MTX not tolerated), Psoriatic arthritis
Major Side Effects	Hepatotoxicity (monitor LFTs monthly for first 6 months), Teratogen (Category X - longer washout needed than MTX), Diarrhoea, Hypertension, Peripheral neuropathy, Alopecia, Rash
Contraindications	Pregnancy (extremely long half-life of active metabolite - requires cholestyramine washout to eliminate; must confirm undetectable levels before conception), Significant hepatic disease, Severe immunodeficiency
Washout	Cholestyramine 8g TDS x 11 days to eliminate drug before pregnancy
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Leflunomide's active metabolite (A77 1726/teriflunomide) has a t½ of 2 years without washout. Must use cholestyramine to eliminate quickly before pregnancy.

5. CONVENTIONAL DMARD QUICK COMPARISON TABLE

DMARD	Main Use	Key Monitoring	Avoid in Pregnancy	Unique Side Effect
Methotrexate	RA anchor drug	FBC, LFTs, Renal, CXR	Yes (stop 3 months before)	MTX pneumonitis; teratogen
Sulfasalazine	RA, IBD, SpA	FBC, LFTs	Relatively safe	Male infertility; orange urine
Hydroxychloroquine	SLE, mild RA	Annual ophthalmology	Safe (continue in pregnancy)	Retinopathy (bull's-eye)
Leflunomide	RA (when MTX fails)	FBC, LFTs, BP	Yes (cholestyramine washout)	Long active metabolite; teratogen

6. BIOLOGIC DMARDs

6a. Anti-TNFα Agents

Mnemonic: "FAINT = Five anti-TNFs: infliximab, Adalimumab, etaNercept, golimumaB, cerTolizumab"

Drug	Class	Route	Key Notes
Infliximab	Chimeric IgG1 mAb (murine + human)	IV infusion	Binds soluble + membrane-bound TNFα; loading doses (0, 2, 6 weeks)
Adalimumab	Fully human IgG1 mAb	SC fortnightly	Most prescribed biologic worldwide; self-injection
Etanercept	TNF receptor fusion protein (IgG1 Fc + 2x TNFR2)	SC weekly	Binds TNFα and TNFβ (lymphotoxin); cannot be used for IBD (unlike infliximab/adalimumab)
Golimumab	Fully human IgG1 mAb	SC monthly or IV	UC specific (IV form), RA, PsA, AS
Certolizumab	PEGylated Fab' fragment	SC	Does not fully cross placenta → relatively safer in late pregnancy; no Fc region → no complement fixation

Feature	Detail
Mechanism	Bind and neutralise TNFα → ↓ downstream inflammatory cascade (NF-κB, cytokines, synovitis)
Key Indications	Moderate-severe RA (after failure of ≥1 conventional DMARD incl. MTX), Psoriatic arthritis, Ankylosing spondylitis, IBD (infliximab/adalimumab), Plaque psoriasis
Major Side Effects	Infection (↑ bacterial, fungal, viral infections - especially TB!), TB reactivation (critical screening required), Injection/infusion site reactions, Drug-induced lupus (anti-dsDNA, ANA; usually mild and reversible), Demyelination (avoid in MS), Worsening HF (avoid in NYHA III-IV), Lymphoma risk (↑ HSTCL with thiopurines + anti-TNF), Skin cancers
Pre-treatment screening	IGRA (TB) + CXR, Hepatitis B serology (reactivation risk), Varicella status, Live vaccines (must complete vaccination schedule before starting)
Contraindications	Active infection (including active TB), NYHA III-IV heart failure, Active demyelinating disease (MS), Active malignancy (within 5 years)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

TB reactivation = #1 concern with anti-TNF; must do IGRA/Mantoux + CXR first; treat LTBI before starting

No live vaccines once on biologics (MMR, varicella, yellow fever, BCG)

Etanercept does NOT work for IBD (different mechanism of TNF binding - only relevant difference from other anti-TNFs clinically)

Drug-induced lupus → check ANA, anti-histone antibodies; resolves on stopping drug

6b. IL-6 Inhibitor: Tocilizumab

Mnemonic: "TOCI = TOCh-screen IL-6 (blocks IL-6 receptor)"

Feature	Detail
Mechanism	Monoclonal antibody against IL-6 receptor (IL-6R) → blocks IL-6 signalling → ↓ inflammation, ↓ acute phase proteins (CRP, ESR, fibrinogen)
Key Indications	Moderate-severe RA (anti-TNF failure or first-line biologic), Giant cell arteritis (IV pulse), Cytokine release syndrome (COVID-19, CAR-T therapy), Systemic JIA
Major Side Effects	Infections (↑ risk), ↑ LFTs (monitor), Hyperlipidaemia (monitor), Neutropaenia, Thrombocytopaenia, Bowel perforation (rare, especially with diverticulitis history), Masks fever (suppresses acute phase response - CRP may be normal even with sepsis)
Contraindications	Active serious infection, Diverticular disease (bowel perforation risk), Hepatic impairment
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Tocilizumab masks CRP and fever → difficult to diagnose infections in patients on this drug. Always consider infection even if CRP normal.

6c. IL-1 Inhibitor: Anakinra

Feature	Detail
Mechanism	Recombinant IL-1 receptor antagonist → blocks IL-1α and IL-1β
Key Indications	RA (third-line; less used now), Adult-onset Still's disease (AOSD - first-line biologic), Cryopyrin-associated periodic syndromes (CAPS), Gout flare (refractory)
Major Side Effects	Injection site reactions (most common - erythema, swelling), Infections, Neutropaenia
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Anakinra = short t½ (daily SC injection); less efficacious in RA than anti-TNF. Mainly tested for use in Adult-onset Still's disease and autoinflammatory conditions.

6d. Anti-CD20: Rituximab

Mnemonic: "RiTUXimab = Removes T-less lymphocytes (B cells with CD20)"

Feature	Detail
Mechanism	Chimeric monoclonal antibody against CD20 on B lymphocytes → B cell depletion → ↓ autoantibodies, ↓ B-cell-mediated inflammation
Key Indications	RA after failure of ≥1 anti-TNF (IV, given every 6-12 months), Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (GPA/MPA), SLE (refractory), Lymphoma (oncology)
Major Side Effects	Infusion reactions (first infusion most common: fever, rigors, hypotension, urticaria - premedicate with methylprednisolone + paracetamol + antihistamine), Severe infections (B cell-depleted for 6-9 months), Progressive multifocal leukoencephalopathy (PML) (JC virus reactivation - rare but fatal), Hypogammaglobulinaemia (with repeated courses)
Contraindications	Active serious infection, Severe HF, Hepatitis B (reactivation risk - screen and prophylax)
HKMLE Paper	Paper I Medicine

HKMLE Pearl: PML (JC virus) = progressive neurological symptoms (cognitive decline, focal deficits) in immunocompromised patient on rituximab/natalizumab → urgent MRI brain.

6e. Anti-CTLA-4: Abatacept

Feature	Detail
Mechanism	CTLA-4-Ig fusion protein → binds CD80/CD86 on APCs → blocks CD28 co-stimulatory signal → prevents T cell activation
Key Indications	Moderate-severe RA (anti-TNF failure or as alternative first biologic), Psoriatic arthritis
Major Side Effects	Infections (↑ COPD exacerbations specifically), Infusion reactions (IV form), Nausea, Headache
Contraindications	Active serious infection; do NOT combine with other biologics (↑ infection without added benefit)
HKMLE Paper	Paper I Medicine

6f. JAK Inhibitors (tsDMARDs)

Mnemonic: "JAKs = Just Act Kinase-inhibitors = oral biologics"

Feature	Detail
Mechanism	Inhibit Janus kinase (JAK) enzymes (JAK1/2/3, TYK2) → block intracellular signalling from multiple cytokine receptors → broad anti-inflammatory effect
Key Indications	Moderate-severe RA (after MTX failure), Psoriatic arthritis, Ankylosing spondylitis (upadacitinib), Atopic dermatitis (baricitinib, upadacitinib)
Drugs	Tofacitinib (JAK1/3), Baricitinib (JAK1/2), Upadacitinib (selective JAK1)
Major Side Effects	Infections (reactivation of herpes zoster - very common! Consider VZV vaccine before starting), VTE/PE (tofacitinib - black box warning, especially in older patients), Malignancy risk (ORAL surveillance trial), Dyslipidaemia, Anaemia, Elevated LFTs
Contraindications	Severe infection, Haemoglobin <9 g/dL (tofacitinib), Active malignancy (within 5 years), VTE history (tofacitinib/baricitinib - relative)
HKMLE Paper	Paper I Medicine

HKMLE Pearl: JAK inhibitors = oral (unlike IV/SC biologics); convenient but multiple black box warnings including VTE and malignancy. Herpes zoster reactivation is the most clinically significant infectious complication (much more than anti-TNF).

7. GOUT DRUGS

Acute Gout Management

Mnemonic: "COIN = Colchicine Or Indomethacin Now" (acute attack treatment)

Drug	Use in Acute Gout	Mechanism	Key Points
NSAIDs (Indomethacin, Naproxen)	First-line (if no CI)	↓ prostaglandin synthesis → ↓ inflammation	Indomethacin = classic NSAID for acute gout; avoid in renal failure, PUD, anticoagulation
Colchicine	First-line (if NSAIDs CI)	See below	Must give within 36 hours of onset; most effective early
Systemic/intra-articular corticosteroids	First-line (when NSAIDs + colchicine contraindicated)	↓ inflammation	Oral prednisolone or IA injection if monoarticular

7a. Colchicine

Mnemonic: "COLCHICINE = COL-chi-CINE = binding tubulin → stops neutrophils from rushing in"

Feature	Detail
Mechanism	Binds tubulin → inhibits tubulin polymerisation → disrupts microtubule formation → inhibits neutrophil migration into inflamed joint; blocks mitotic spindle → anti-proliferative
Key Indications	Acute gout (within 36 hours of attack onset), Prophylaxis during initiation of urate-lowering therapy (prevents flare), Familial Mediterranean Fever (FMF - long-term prevention), Pericarditis (adjunct to NSAIDs)
Major Side Effects	Diarrhoea (most common; dose-limiting - use to guide dosing), Nausea/vomiting, Abdominal pain; Overdose/chronic toxicity: Myopathy, Peripheral neuropathy, Myelosuppression (aplastic anaemia), Alopecia
Contraindications	Severe renal/hepatic impairment, Pregnancy (teratogen), Concurrent CYP3A4 inhibitors (clarithromycin, itraconazole - ↑ colchicine levels → toxicity; dose reduce!)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

"Diarrhoea = signal to stop or reduce colchicine dose" - classic exam fact

Modern low-dose regimen (1.2mg then 0.6mg 1h later) = as effective as high-dose with fewer GI side effects

CYP3A4 inhibitors (clarithromycin, diltiazem, verapamil, itraconazole) ↑ colchicine levels → serious toxicity

Not effective if given >36-48 hours after attack onset

7b. Urate-Lowering Therapy (Chronic Gout)

Indication to start ULT: ≥2 attacks/year, tophi, uric acid nephrolithiasis, CKD, or radiographic joint damage

Key rule: Start ULT 2-4 weeks AFTER acute attack resolves; starting during attack can prolong/worsen flare. Always co-prescribe colchicine or NSAID prophylaxis for at least 6 months when starting ULT.

Allopurinol

Mnemonic: "ALLO = ALLows Output of less uric acid (xanthine oxidase inhibitor)"

Feature	Detail
Mechanism	Competitive inhibitor of xanthine oxidase → ↓ conversion of hypoxanthine → xanthine → uric acid
Key Indications	First-line ULT for gout (overproducers AND underexcretors), Uric acid nephrolithiasis, Tumour lysis syndrome prevention
Major Side Effects	Rash (common; mild), DRESS syndrome/Stevens-Johnson syndrome (rare but severe - especially with *HLA-B5801** in Han Chinese, Korean, Thai patients - screen before use!), Hypersensitivity reactions, GI upset; allopurinol can precipitate acute gout flare when starting
Drug Interactions	Azathioprine/6-MP - allopurinol inhibits xanthine oxidase which metabolises AZA/6-MP → severe myelosuppression (reduce AZA dose by 75% if combined, or avoid)
Contraindications	None absolute; caution in renal impairment (start at low dose 50-100mg and titrate)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

HLA-B*5801 = strong association with severe allopurinol hypersensitivity (SJS/DRESS) in Southeast Asian and Han Chinese populations; HKMLE-relevant - screen these populations before starting allopurinol

Allopurinol + azathioprine/6-MP = DANGEROUS COMBINATION (4x ↑ azathioprine toxicity) - reduce dose by 75% or switch to febuxostat

Target uric acid <360 µmol/L (<6 mg/dL) in non-tophaceous gout; <300 µmol/L in tophaceous gout

Febuxostat

Feature	Detail
Mechanism	Non-purine selective inhibitor of xanthine oxidase (both oxidised and reduced forms) → ↓ uric acid synthesis
Key Indications	Gout (second-line to allopurinol, or when allopurinol not tolerated), Gout in mild-moderate CKD (safer than allopurinol in CKD)
Major Side Effects	Gout flares on initiation, GI upset, Rash, ↑ CV events (black box warning - ↑ CV death vs allopurinol in FAST/CARES trial; use with caution in CVD)
Drug Interactions	Same as allopurinol with AZA/6-MP (also inhibits xanthine oxidase)
HKMLE Paper	Paper I Medicine

Probenecid (Uricosuric)

Feature	Detail
Mechanism	Inhibits URAT1 and OAT transporters in proximal tubule → blocks uric acid reabsorption → ↑ renal uric acid excretion (uricosuric)
Key Indications	Gout (underexcretors; second/third-line when XO inhibitors contraindicated or insufficient)
Major Side Effects	GI upset, Rash, Uric acid nephrolithiasis (↑ urinary uric acid → stones), Headache
Contraindications	Uric acid kidney stones, Impaired renal function (eGFR <30 - doesn't work), Overproducers (↑ urinary load)
Drug Interactions	Inhibits renal secretion of many drugs: ↑ penicillin (historical use to prolong penicillin), ↑ MTX, ↑ NSAIDs; Aspirin blocks uricosuric effect (low-dose aspirin competes)
HKMLE Paper	Paper I Medicine

HKMLE Pearl: Low-dose aspirin antagonises probenecid (compete for same transporter). Do NOT use probenecid in uric acid stone formers.

Pegloticase

Feature	Detail
Mechanism	PEGylated recombinant uricase → converts uric acid to allantoin (highly soluble → easily excreted)
Key Indications	Severe refractory tophaceous gout when all other ULTs fail
Major Side Effects	Infusion reactions (common, including anaphylaxis - premedicate), Gout flares, G6PD deficiency → haemolysis (contains PEG)
HKMLE Paper	Paper I Medicine

8. GOUT MANAGEMENT QUICK REFERENCE

Phase	Treatment
Acute attack	NSAIDs (indomethacin/naproxen) OR Colchicine (low dose) OR Prednisolone; do NOT start or stop ULT during acute attack
Starting ULT	Wait 2-4 weeks after attack resolves; co-prescribe colchicine prophylaxis for ≥6 months
First-line ULT	Allopurinol (start low 50-100mg, titrate to target serum urate)
Allopurinol failure/intolerance	Febuxostat or Probenecid
Refractory tophaceous gout	Pegloticase IV
Lifestyle	↓ Purine-rich foods (red meat, offal, shellfish, oily fish), ↓ Alcohol (especially beer), ↓ Fructose drinks, Adequate hydration

Drugs that RAISE uric acid (cause/worsen gout)

Mnemonic: "PLANT CT" = Pyrazinamide, Loop diuretics, Aspirin (low dose), Nicotinic acid, Thiazides, Ciclosporin/tacrolimus, Tacrolimus (calcineurin inhibitors)

9. OSTEOARTHRITIS DRUGS

Drug/Class	Mechanism	Use	Notes
Paracetamol	CNS COX inhibition	Mild-moderate OA pain (first-line simple analgesic)	Regular dosing preferred; less effective than NSAIDs in OA
Topical NSAIDs (diclofenac gel, ibuprofen gel)	Local COX inhibition	First-line pharmacological treatment in knee/hand OA (NICE recommends topical before oral NSAIDs)	↓ Systemic side effects vs oral NSAIDs; preferred in elderly
Oral NSAIDs	COX-1/2 inhibition	Moderate-severe OA pain not controlled by topical/paracetamol	Use lowest effective dose for shortest time; gastroprotection with PPI
Duloxetine	SNRI → central pain sensitisation inhibition	Chronic OA pain (when NSAIDs contraindicated/failed)	Evidence for knee OA and chronic musculoskeletal pain; improves central sensitisation
Intra-articular corticosteroids	↓ Local inflammation	Acute OA flares (knee, hip)	Rapid symptom relief; repeat injections ≤4/year (cartilage damage risk with more frequent use)
Intra-articular hyaluronic acid	Viscoelastic supplement → ↑ joint lubrication	Knee OA (controversial evidence; NICE does NOT recommend - limited benefit over placebo)	"Viscosupplementation"; may benefit some patients; 3-5 weekly injections
Glucosamine + Chondroitin	Cartilage precursors	OA (controversial; limited evidence)	OTC; variable response; generally safe

HKMLE Pearls:

Topical diclofenac = first-line pharmacological treatment for knee OA before oral NSAIDs (NICE/EULAR guidelines)

NICE does NOT recommend hyaluronic acid injections for OA (insufficient evidence vs placebo in large trials)

Duloxetine = useful for OA patients with central sensitisation/chronic pain syndrome

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
Paracetamol overdose → NAC treatment	Paper I / Paper II	Emergency management
NSAIDs in pregnancy (avoid T3, PDA closure)	Paper I / Paper III OG	Contraindication scenario
Indomethacin = closes PDA (neonates + T3 mechanism)	Paper I / Paper III	Dual-role MCQ
Celecoxib + sulfonamide allergy	Paper I Medicine	Contraindication scenario
COX-2 → ↑ CV risk (rofecoxib withdrawn)	Paper I Medicine	Drug safety/history
MTX pneumonitis + stop immediately	Paper I Medicine	Complication identification
MTX + folic acid (must co-prescribe)	Paper I Medicine	Monitoring/co-prescription
MTX teratogen (stop 3 months before conception)	Paper I / Paper III	Pregnancy safety
HCQ retinopathy monitoring (annual ophthalmology)	Paper I Medicine	Monitoring protocol
HCQ safe in SLE pregnancy	Paper III OG	Safe drug in pregnancy
Allopurinol + azathioprine interaction	Paper I Medicine	Drug interaction
HLA-B*5801 + allopurinol (Asian patients)	Paper I Medicine	Pharmacogenomics MCQ
Colchicine must be given <36h; diarrhoea = dose-guide	Paper I Medicine	Drug administration
TB screening before anti-TNF	Paper I Medicine	Pre-treatment protocol
JAK inhibitors + herpes zoster risk	Paper I Medicine	Side effect identification
Tocilizumab masks CRP/fever	Paper I Medicine	Drug monitoring trap
Topical NSAIDs = first-line in knee OA	Paper I Medicine	Drug selection

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
Paracetamol OD treatment	NAC = N-Acetylcysteine (replenishes glutathione)
NSAIDs avoid in	"GUT RAPS" = GI bleed, sUlfonamide allergy (celecoxib), Third trimester, Renal failure, Aspirin-exacerbated asthma, Platelet disorder, Severe HF
MTX key rules	"FLM3" = Folic acid weekly, Liver/lung/marrow monitor, Must stop 3 months before pregnancy
HCQ monitoring	"Eyes Every year after 5" = annual ophthalmology from year 5
Leflunomide washout	"Cholestyramine washes LEF away"
Anti-TNF pre-screening	"TBH" = TB screen (IGRA), Blood (Hep B), Herd immunity (live vaccines first)
Gout acute	"COIN" = Colchicine Or Indomethacin Now (within 36h)
Allopurinol + AZA	"AZA on ALLO = ↓ AZA by 75% or STOP"
HLA-B*5801	"Asian patient + Allopurinol = check HLA first (SJS risk)"
Drugs that raise uric acid	"PLANT CT" = Pyrazinamide, Loop diuretics, Aspirin (low), Nicotinic acid, Thiazides, Calcineurin inhibitors (ciclosporin, tacrolimus)
DMARDs in pregnancy	"HCQ = Happy, MTX/LEF = No way"

Sources: Lippincott Illustrated Reviews Pharmacology; Katzung's Basic and Clinical Pharmacology 16th Edition; Harrison's Principles of Internal Medicine 22E (2025); Goldman-Cecil Medicine.

Give me high-yield HKMLE notes on Haematology Pharmacology with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - Anticoagulants (warfarin, DOACs: apixaban, rivaroxaban, edoxaban, dabigatran) - Antiplatelets (aspirin, clopidogrel, ticagrelor, prasugrel, dipyridamole) — only if not fully covered in Cardio - Thrombolytics (alteplase, tenecteplase, streptokinase) - Haematinics (iron, vitamin B12, folate) - Growth factors (erythropoietin, G-CSF/filgrastim, thrombopoietin agonists) - Antifibrinolytics (tranexamic acid, aminocaproic acid) - Heparin (unfractionated, LMWH: enoxaparin) and protamine reversal - Direct thrombin inhibitors (bivalirudin, argatroban) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Antibiotics notes.

Finding Sources

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

I now have all the data I need. Let me compile the complete notes.

High-Yield HKMLE: Haematology Pharmacology Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): Most haematology pharmacology - anticoagulants, DOACs, reversal agents, haematinics, growth factors

Paper II Surgery/Emergency (45 MCQs): Perioperative anticoagulation management, thrombolytics, TXA in trauma, bridging therapy, HIT management

Paper III Paediatrics/OG (30 MCQs): Anticoagulation in pregnancy (LMWH safe; warfarin/DOACs unsafe), iron/B12/folate in pregnancy

MASTER MAP: HAEMATOLOGY PHARMACOLOGY

Mnemonic: "WATCH A GRIP"

Warfarin (VKA)
Anticoagulants - DOACs (Xa + IIa inhibitors)
Thrombolytics (tPA agents)
Clot stabilisers (Antifibrinolytics: TXA)
Heparin (UFH + LMWH) + direct thrombin inhibitors
Antiplatelets (ASA, clopidogrel, ticagrelor)
Growth factors (EPO, G-CSF, TPO agonists)
Reversal agents (protamine, idarucizumab, andexanet, vitamin K, PCC)
Iron, B12, Folate (haematinics)
Platelets/fibrin system (coagulation cascade context)

1. WARFARIN (Vitamin K Antagonist)

Mnemonic: "WEPT = Warfarin: Extended PT, inhibits 1972 (factors II, VII, IX, X + Proteins C and S)"

Feature	Detail
Mechanism	Inhibits vitamin K epoxide reductase → blocks activation of vitamin K-dependent clotting factors II, VII, IX, X and anticoagulant proteins C and S
Onset	Delayed - takes 3-5 days (must bridge with heparin/LMWH); factor VII has shortest half-life (6h) - INR rises first but not fully anticoagulated yet
Monitoring	INR (target range depends on indication - see below)
Key Indications	Atrial fibrillation (target INR 2-3), DVT/PE treatment and prevention (INR 2-3), Mechanical heart valves (INR 2.5-3.5), Antiphospholipid syndrome (INR 2-3 or 3-4 if recurrent thrombosis)
Major Side Effects	Bleeding (all sites; GI, intracranial = most dangerous), Skin necrosis (early in therapy - due to ↓ Protein C/S before full anticoagulation; especially in protein C deficiency → warfarin must always be started with heparin), Teratogen - Category X (warfarin embryopathy: nasal hypoplasia, stippled epiphyses, fetal haemorrhage)
Contraindications	Pregnancy (all trimesters), Active bleeding, Recent intracranial surgery/haemorrhage
Drug Interactions	Enormous (CYP2C9 mediated) - see table below
HKMLE Paper	Paper I Medicine, Paper II Surgery, Paper III OG

Warfarin INR Targets

Indication	Target INR
AF, DVT/PE	2.0 - 3.0
Mechanical mitral valve	2.5 - 3.5
Mechanical aortic valve	2.0 - 3.0 (some guidelines 2.5-3.5)
Recurrent PE/APS	2.5 - 3.5

Warfarin Drug Interactions (HIGH YIELD)

Mnemonic: "WIPE = Warfarin Increased by Potentiators: Erythro/Azithromycin, amiodarone, metronidazole, fluconazole, etc."

Effect on INR	Drug Examples	Mechanism
↑ INR (↑ bleeding risk)	Amiodarone, fluconazole, metronidazole, ciprofloxacin, clarithromycin, SSRIs, statins (fluvastatin, simvastatin), fish oil, alcohol (acute binge)	Inhibit CYP2C9 (warfarin metabolism)
↓ INR (↓ efficacy)	Rifampicin, phenytoin, carbamazepine, phenobarbital, St John's Wort, alcohol (chronic), griseofulvin	Induce CYP2C9
Variable INR	NSAIDs (↑ bleeding risk without changing INR via platelet inhibition)	GI mucosa + platelet effect

Warfarin Reversal

INR / Scenario	Action
INR 3-5, no bleeding	Reduce or omit dose, recheck in 1-2 days
INR 5-8, no significant bleeding	Stop warfarin, give low-dose oral vitamin K 1-2mg
INR >8, no/minor bleeding	Stop warfarin, give oral vitamin K 5mg (repeat if INR still high at 24h)
Any INR + major bleeding	Stop warfarin + IV vitamin K 5-10mg + 4-factor Prothrombin Complex Concentrate (PCC) (preferred over FFP - faster, lower volume)
Life-threatening intracranial bleed	PCC + IV vitamin K 10mg immediately

HKMLE Pearls:

Protein C/S have short half-lives → warfarin first causes a transient procoagulant state → always bridge with heparin when starting warfarin in acute thrombosis

Warfarin embryopathy occurs between weeks 6-12; fetal haemorrhage risk in T3 → DOACs also contraindicated → LMWH is the only safe anticoagulant in pregnancy

INR measures extrinsic pathway (factors VII, X, II, V, fibrinogen)

2. HEPARIN - UNFRACTIONATED (UFH) AND LMWH

Mnemonic: "HEPARIN = Helps Every Patient And Requires INR-free monitoring (except UFH)"

Comparison Table: UFH vs LMWH

Feature	UFH (Unfractionated Heparin)	LMWH (e.g. Enoxaparin)
Mechanism	Binds antithrombin III → inhibits IIa (thrombin) and Xa (and IXa, XIa, XIIa)	Binds antithrombin III → preferentially inhibits factor Xa (smaller chain cannot bridge thrombin)
Route	IV infusion or SC	SC only (enoxaparin can be IV in STEMI)
Monitoring	aPTT (target 1.5-2.5x normal)	Usually NOT required; Anti-Xa level if obese, pregnant, or renal impairment
Half-life	~1.5 hours (IV)	3-12 hours
Reversal	Protamine sulfate (neutralises fully)	Protamine sulfate (only ~60% neutralised)
Safe in Pregnancy	Yes - does NOT cross placenta	Yes - preferred in pregnancy (does not cross placenta; more predictable)
Renal clearance	No (reticuloendothelial metabolism)	Yes - accumulates in renal failure → reduce dose/avoid if eGFR <30
HIT risk	Higher (5-10 days, Type II)	Lower but still possible
Use preference	ICU, unstable patients, perioperative, when rapid reversal needed	DVT/PE treatment, VTE prophylaxis, ACS, outpatient

Heparin-Induced Thrombocytopenia (HIT) - HIGH YIELD

Mnemonic: "HIT = Heparin Induces Thrombosis (paradoxically) - the 4Ts score"

Feature	Detail
Type I (non-immune)	Mild ↓ platelets (>100), within 1-2 days; non-immune; benign; continue heparin
Type II (immune, HIT)	Platelet count ↓ >50% from baseline, typically days 5-10 of first heparin use; IgG antibodies against heparin-PF4 complex → platelet activation → paradoxical thrombosis (not just bleeding!)
Diagnosis	4Ts score (Thrombocytopenia, Timing, Thrombosis, other causes excluded); confirm with anti-PF4/heparin ELISA or serotonin release assay
Management	Stop ALL heparin immediately (UFH AND LMWH); start alternative anticoagulant: argatroban or fondaparinux; do NOT give platelets (unless life-threatening bleed); do NOT start warfarin until platelets >150 (risk of venous limb gangrene)
Future exposure	Contraindicated - both UFH and LMWH; use fondaparinux or DOAC

HKMLE Pearls:

HIT causes THROMBOSIS not just low platelets - this is the paradox

Platelet transfusions are CONTRAINDICATED in HIT (worsen thrombosis)

4Ts score: Thrombocytopenia severity, Timing (day 5-10), Thrombosis, other causes of Thrombocytopenia

Warfarin should not be started in HIT until platelets normalise (→ Protein C depletion → venous limb gangrene)

3. DIRECT THROMBIN INHIBITORS (DTIs)

Drug	Route	Key Use	Notes
Argatroban	IV infusion	HIT (alternative anticoagulant); hepatic elimination → use in renal failure	No reversal agent; stop infusion (short t½ ~50min)
Bivalirudin	IV infusion	PCI (percutaneous coronary intervention) - alternative to heparin	Short-acting; renal elimination; no reversal agent
Dabigatran	Oral	See DOAC section below	Reversal: idarucizumab

Feature	Detail
Mechanism (all)	Directly inhibit thrombin (factor IIa) → block fibrin formation, thrombin-mediated platelet activation; act independently of antithrombin (unlike heparin)
Advantage	Work in HIT (no heparin cofactor needed), predictable dosing, no PF4-antibody issues

HKMLE Pearl: Argatroban = drug of choice for HIT in renal failure (hepatic elimination). Fondaparinux = also used in HIT (factor Xa inhibitor; no cross-reactivity with PF4 antibodies).

4. DIRECT ORAL ANTICOAGULANTS (DOACs)

Mnemonic: "3 XAs + 1 IIA = Rivaroxaban, Apixaban, Edoxaban (all Xa inhibitors) + Dabigatran (IIa inhibitor)"

Master DOAC Comparison Table

Feature	Dabigatran	Rivaroxaban	Apixaban	Edoxaban
Target	Factor IIa (thrombin)	Factor Xa	Factor Xa	Factor Xa
Bioavailability	6% (low!)	80%	50%	55%
Half-life	14-17h	7-11h	8-14h	8-10h
Renal clearance	80% renal (most renally cleared)	~33% renal	~27% renal	~50% renal
Monitoring	Not routinely needed (modified thrombin time if needed)	Not routinely needed (anti-Xa assay if needed)	Not routinely needed (anti-Xa assay)	Not routinely needed (anti-Xa assay)
Drug interactions	P-gp inducers/inhibitors	P-gp AND CYP3A4	P-gp AND CYP3A4	P-gp inducers/inhibitors
Reversal agent	Idarucizumab (5g IV; Praxbind)	Andexanet alfa	Andexanet alfa	Andexanet alfa (or PCC if unavailable)
Oral dosing	Twice daily	Once daily (AF); twice daily (DVT/PE acute)	Twice daily	Once daily

DOAC Common Features (applies to ALL)

Feature	Detail
Key Indications	AF (stroke prevention - non-valvular only), DVT/PE treatment and prevention, Post-surgical VTE prophylaxis
Major Side Effect	Bleeding (GI bleeding particularly high with dabigatran and rivaroxaban vs warfarin)
Contraindications	Pregnancy (teratogenic; crosses placenta) → use LMWH instead; mechanical heart valves (DOACs inferior to warfarin - RE-ALIGN trial); antiphospholipid syndrome (warfarin preferred for triple-positive APS); severe renal impairment (especially dabigatran - 80% renal)
Advantages over warfarin	No routine monitoring, fewer drug interactions, predictable dosing, faster onset/offset, lower risk of intracranial haemorrhage
Disadvantages vs warfarin	More expensive, renal clearance dependency, no universal reversal (though specific antidotes now exist)

DOAC Renal Dose Adjustment (HKMLE Pearl)

Mnemonic: "Dabigatran = Danger in renal failure (avoid if CrCl <30); Apixaban = safest in CKD (least renally cleared)"

DOAC	Action in Renal Impairment
Dabigatran	Avoid if CrCl <30 mL/min (80% renal)
Rivaroxaban	Avoid if CrCl <15 mL/min (AF); reduce dose in moderate CKD
Apixaban	Dose reduce if 2 of: age ≥80, weight ≤60kg, creatinine ≥133 µmol/L
Edoxaban	Dose reduce if CrCl 15-50 mL/min

DOAC Reversal Agents

Situation	Agent	Notes
Dabigatran major bleeding	Idarucizumab 5g IV (monoclonal Ab Fab fragment - binds dabigatran)	Approved; immediate reversal
Rivaroxaban/Apixaban major bleeding	Andexanet alfa (recombinant factor Xa decoy - binds Xa inhibitors)	Approved; or use 4F-PCC 25-50 units/kg if unavailable
Edoxaban major bleeding	Andexanet alfa or 4F-PCC
Any DOAC + minor bleeding	Hold drug, local measures, supportive care
Any DOAC + activated charcoal	If taken ≤2h ago (especially dabigatran)

HKMLE Pearls:

DOACs are NOT safe in mechanical heart valves (only warfarin)

DOACs are NOT safe in pregnancy (LMWH is the only safe anticoagulant)

Dabigatran = only oral DTI (all others = Xa inhibitors)

Idarucizumab = specific for dabigatran only; andexanet alfa = for all Xa inhibitors

St John's Wort, rifampicin, carbamazepine reduce all DOAC efficacy (P-gp/CYP3A4 induction) → avoid combination

5. ANTIPLATELETS

(Core concepts for HKMLE - detailed CVS notes already covered)

Antiplatelet Overview Table

Drug	Mechanism	Onset/Offset	Key Use	HKMLE-Specific Notes
Aspirin	Irreversibly inhibits COX-1 → ↓ TXA2 → ↓ platelet aggregation (lifelong platelet affected - 7-10 days)	Irreversible (7-10 days - lifespan of platelet)	ACS, AF (low efficacy; warfarin preferred), secondary stroke prevention, post-PCI	Low dose 75-150mg daily; high dose = anti-inflammatory; never in children <12 (Reye's)
Clopidogrel	Irreversibly blocks P2Y12 ADP receptor on platelets	Irreversible (7-10 days); prodrug - requires CYP2C19 activation	ACS, post-PCI (DAPT with aspirin), AF (if warfarin/DOAC intolerant), PAD	CYP2C19 poor metabolisers = reduced efficacy (pharmacogenomics); PPIs reduce efficacy (CYP2C19 competition)
Ticagrelor	Reversibly blocks P2Y12; NOT a prodrug	Reversible (3-5 days)	ACS (preferred over clopidogrel in PLATO trial), post-PCI	More potent; causes dyspnoea (adenosine-mediated; not bronchospasm); do NOT use high-dose aspirin with ticagrelor (reduces efficacy)
Prasugrel	Irreversibly blocks P2Y12; prodrug (more efficient activation than clopidogrel)	Irreversible (7-10 days)	STEMI post-PCI (preferred in TRITON trial)	Contraindicated if prior stroke/TIA (↑ intracranial bleed), age >75, weight <60kg; most potent P2Y12 blocker
Dipyridamole	Inhibits phosphodiesterase → ↑ cAMP → ↓ platelet aggregation; also blocks adenosine reuptake; vasodilatory	Reversible	Secondary stroke prevention (combined with aspirin = Aggrenox), cardiac stress testing (pharmacological agent)	Dipyridamole stress test = dilates coronary arteries → reveals ischaemia (adenosine analogue effect)
Tirofiban / Eptifibatide	Block GPIIb/IIIa receptor (final common platelet aggregation pathway)	IV; short-acting	High-risk ACS/PCI (adjunct)	IV only; not oral; GPIIb/IIIa = "last resort"

HKMLE Pearls:

DAPT = Dual antiplatelet therapy (aspirin + P2Y12 inhibitor): standard post-ACS/PCI for 12 months

Ticagrelor dyspnoea = adenosine-mediated, not bronchospasm; do NOT switch to clopidogrel without reason

Prasugrel contraindicated in prior TIA/stroke (high intracranial bleed risk)

Stop antiplatelets 7-10 days before elective surgery (clopidogrel/prasugrel); aspirin may be continued for most procedures

6. THROMBOLYTICS (Fibrinolytics)

Mnemonic: "tPA = turns Plasminogen to Active plasmin → eATs fibrin clots"

Feature	Detail
Mechanism (class)	Activate plasminogen → plasmin → plasmin cleaves fibrin → dissolves clots

Individual Thrombolytic Agents

Drug	Type	Key Features
Alteplase (tPA)	Recombinant tissue plasminogen activator (rt-PA)	Gold standard; fibrin-selective; used in ischaemic stroke (within 4.5h) and massive PE and STEMI (if no PCI available); short t½ (5 min) → IV infusion
Tenecteplase (TNK-tPA)	Modified tPA	Longer t½ → single IV bolus (more convenient for STEMI); similar efficacy to alteplase; increasingly used for ischaemic stroke (NOR-TEST/TASTE trials)
Streptokinase	Bacterial protein (Streptococcus) - NOT fibrin specific	Binds plasminogen → complex activates plasminogen; antigenic → allergic reactions; can only be used once (antibodies formed → reuse within 5 years ineffective); cheapest; rarely used now
Reteplase	Deletion mutant of tPA	Double IV bolus; used in STEMI

Thrombolytic Indications and Contraindications

Indication	Preferred Agent	Time Window
Ischaemic stroke	Alteplase (or tenecteplase)	≤4.5 hours from onset
Massive PE with haemodynamic compromise	Alteplase	ASAP
STEMI (if PCI unavailable)	Tenecteplase or streptokinase	≤12 hours from onset (ideally <6h)
Submassive PE (RV strain, no shock)	CONTRAVERSIAL - anticoagulation usually first	-

Absolute Contraindications to Thrombolytics

Mnemonic: "BRAIN HURTS" = Bleeding, Recent surgery/trauma, Aortic dissection, Intracranial history, Neurosurgery recent, Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time window exceeded, Severe bleeding disorder

Absolute Contraindication
Any prior intracranial haemorrhage
Ischaemic stroke within 3 months
Suspected aortic dissection
Active internal bleeding (not menstruation)
Significant closed head injury/trauma within 3 months
Intracranial neoplasm, AVM, or aneurysm

Major Relative Contraindication
SBP >180 or DBP >110 mmHg (uncontrolled)
Recent (2-4 weeks) major surgery or trauma
Active peptic ulcer / recent GI bleed
Pregnancy
Current anticoagulant use
CPR >10 minutes

HKMLE Pearls:

Streptokinase = antigenic → do not repeat within 5 years; allergy = anaphylaxis; rarely used now

For ischaemic stroke: alteplase = standard within 4.5h; door-to-needle time <60 min; must exclude haemorrhage by CT first (CT head before giving thrombolysis)

BP must be controlled <185/110 before giving stroke thrombolysis

Thrombolytics dissolve ALL clots (fibrin-non-selective agents worst) → major bleeding risk

7. ANTIFIBRINOLYTICS

Mnemonic: "TXA = Tranexamic acid eXActs its effect by Blocking plasmin"

Tranexamic Acid (TXA)

Feature	Detail
Mechanism	Synthetic lysine analogue → competitively inhibits plasminogen activation (blocks lysine-binding sites on plasminogen/plasmin) → prevents fibrin clot breakdown → preserves haemostasis
Key Indications	Trauma haemorrhage (CRASH-2 trial: ↓ mortality if given within 3h of injury - NNT ~67), Postpartum haemorrhage (WOMAN trial: ↓ death from bleeding if given early), Heavy menstrual bleeding (oral TXA), Elective surgery (pre/intra-op: cardiac, orthopaedic - ↓ transfusion need), Hereditary angioedema (prophylaxis)
Major Side Effects	Nausea/vomiting (GI), VTE risk (thrombotic concern; avoid in patients with DIC or active thrombosis), Colour vision changes (rare), Seizures at high doses
Contraindications	Active thromboembolic disease (DVT, PE, stroke), DIC with consumption (blocking fibrinolysis worsens DIC), Haematuria from upper urinary tract (blood clots in ureter)
Key Trial	CRASH-2: TXA ≤3h from trauma → ↓ all-cause mortality; given after 3h → no benefit or harm
HKMLE Paper	Paper I Medicine, Paper II Surgery, Paper III OG

HKMLE Pearls:

TXA in PPH: WOMAN trial showed ↓ death from bleeding if given early; now WHO recommended

TXA must be given within 3 hours of trauma (CRASH-2); after 3h = no mortality benefit

Not an anticoagulant reversal agent; does not replace blood products

Aminocaproic acid = similar mechanism to TXA; used in haemophilia bleeds; less commonly tested

8. HAEMATINICS

8a. Iron

Mnemonic: "FERRIC = Ferrous is absorbed, Ferritin stores it, Restores Hb, Iron deficiency = Check cause, Constipation = side effect"

Feature	Detail
Mechanism	Elemental iron required for haemoglobin synthesis (haem moiety); repletes depleted iron stores
Forms	Oral: ferrous sulfate (ferrous = Fe2+ = better absorbed than ferric Fe3+); Parenteral: ferric carboxymaltose, iron sucrose (IV)
Key Indications	Iron deficiency anaemia (most common anaemia worldwide), prevention in pregnancy
Monitoring	Hb should rise by ~10-20g/L per 3 weeks; ferritin (stores), TSAT (transferrin saturation); MCV (microcytic); reticulocyte count ↑ at 1 week (reticulocyte crisis = response marker)
Major Side Effects	GI: nausea, epigastric pain, constipation (most common complaint, can use ferrous gluconate - gentler), diarrhoea, dark stools; IV iron: infusion reactions (anaphylaxis rare but serious with older formulations), transient hypophosphataemia (ferric carboxymaltose)
Drug Interactions	Antacids/PPIs/tea/calcium ↓ iron absorption (chelation); take iron on empty stomach with vitamin C (ascorbic acid ↑ Fe3+→Fe2+ conversion)
Contraindications	Haemochromatosis, haemolytic anaemia (iron not usually deficient)
HKMLE Paper	Paper I Medicine, Paper III OG

Oral Iron Preparation	Notes
Ferrous sulfate 200mg (65mg elemental Fe)	First-line; cheapest
Ferrous gluconate	Gentler on GI; lower elemental iron
Ferrous fumarate	Intermediate

HKMLE Pearls:

Take iron on empty stomach; with Vitamin C (↑ absorption); avoid tea/coffee/antacids (chelate iron)

Dark stools = harmless; warn the patient

IV iron indicated: oral failure/intolerance, IBD, CKD on dialysis, severe deficiency in pregnancy, bariatric surgery

Always identify and treat the cause of IDA (GI cancer? Menorrhagia? Malabsorption?)

8b. Vitamin B12 (Cobalamin)

Mnemonic: "B12 = Big red cells (macrocytic), Bad nerves (subacute combined degeneration), Bypass stomach (intrinsic factor needed)"

Feature	Detail
Mechanism	Cofactor for DNA synthesis (methylcobalamin → methionine synthesis) and myelin formation (adenosylcobalamin → succinyl-CoA → Krebs cycle)
Key Indications	Pernicious anaemia (autoimmune destruction of gastric parietal cells → absent intrinsic factor → can't absorb dietary B12), Dietary deficiency (strict vegans), Post-gastrectomy, Terminal ileum disease (Crohn's, resection - site of B12 absorption), Malabsorption
Formulation	IM hydroxocobalamin (preferred; 1mg IM alternate days x2 weeks, then every 3 months lifelong in pernicious anaemia); oral cyanocobalamin (for dietary deficiency only)
Major Side Effects	Very safe; IM injections uncomfortable; hypokalaemia can occur on starting treatment (B12 stimulates RBC production → ↑ K+ uptake)
Deficiency features	Macrocytic anaemia + hypersegmented neutrophils, Subacute combined degeneration of spinal cord (posterior columns + lateral corticospinal tracts): bilateral paraesthesiae, ataxia, spasticity, extensor plantar responses; glossitis ("beefy red tongue"), megaloblastic changes
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Folate should NEVER be given alone when B12 deficiency is possible - folic acid treats the blood picture but UNMASKS subacute combined degeneration of cord (neurological deterioration)

Pernicious anaemia = anti-intrinsic factor antibodies (most specific) + anti-parietal cell antibodies

Schilling test (now rarely done) = tests IF absorption

8c. Folate (Folic Acid)

Mnemonic: "FOLATE = First trimester supplement, Only treats blood (not neuro), Looks same as B12 anaemia, Avoid in B12 deficiency alone, Treatment oral"

Feature	Detail
Mechanism	Required for one-carbon transfer reactions → DNA synthesis; converted to THF → needed for purine/pyrimidine synthesis
Key Indications	Neural tube defect prevention (5mg/day preconception + T1 for high-risk; 400mcg/day standard); treatment of folate deficiency anaemia; prophylaxis in haemolytic anaemia (↑ RBC turnover), Methotrexate co-prescription (5mg weekly)
Deficiency causes	Poor diet, Pregnancy (↑ demands), Alcohol (most common cause in HK/Western settings), Malabsorption (coeliac), Methotrexate (DHFR inhibition), Trimethoprim, Phenytoin, Methotrexate
Major Side Effects	Very safe; large doses may mask B12 deficiency → neurological harm
HKMLE Paper	Paper I Medicine, Paper III OG

Population	Folate Dose
Standard preconception/T1 pregnancy	400 mcg (0.4mg) daily
High-risk (previous NTD, diabetes, antiepileptics, obesity)	5mg daily
MTX co-prescription	5mg once weekly

HKMLE Pearl: Alcoholism = most common cause of folate deficiency in clinical practice. Folate + B12 both give macrocytic anaemia - differentiate with B12/folate levels + neurological features (B12 deficiency = neuro symptoms; folate deficiency = no neuro).

9. HAEMATOPOIETIC GROWTH FACTORS

9a. Erythropoietin / Erythropoiesis-Stimulating Agents (ESAs)

Mnemonic: "EPO = Every Patient On dialysis needs this"

Feature	Detail
Mechanism	Recombinant human erythropoietin (epoetin alfa/beta/darbepoetin alfa) → binds EPO receptor on erythroid progenitors in bone marrow → stimulates RBC production
Key Indications	Anaemia of chronic kidney disease (CKD; primary use), Chemotherapy-induced anaemia (haematology-oncology), Myelodysplastic syndrome (low-risk), Autologous blood donation pre-surgery
Major Side Effects	Hypertension (most common; ↑ Hb → ↑ viscosity → ↑ BP), Thrombotic events (VTE, stroke - especially if Hb overcorrected >120-130g/L), Pure red cell aplasia (PRCA) (rare: anti-EPO antibodies → stop EPO, immunosuppression), Flu-like symptoms, Headache
Monitoring	Hb level (target 100-120g/L in CKD, do NOT exceed 130g/L - ↑ CV events shown in CHOIR and CREATE trials), Blood pressure
Must co-prescribe	Iron (iron deficiency limits ESA response; check ferritin and TSAT before and during treatment)
Contraindications	Uncontrolled hypertension, Active malignancy (some tumours express EPO receptors), Haemoglobin already adequate
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Target Hb in CKD: 100-120g/L - do NOT target normal Hb (↑ VTE and CV mortality)

Always check iron stores before starting EPO - if iron deficient, EPO will not work and wastes cost

PRCA = rare but serious; presents as sudden worsening anaemia after initial response; check anti-EPO antibodies

9b. G-CSF (Granulocyte Colony-Stimulating Factor): Filgrastim / Pegfilgrastim

Mnemonic: "G-CSF = Grows White cells (neutrophils)"

Feature	Detail
Mechanism	Binds G-CSF receptor → stimulates proliferation, differentiation, and survival of neutrophil precursors → ↑ mature neutrophil release from bone marrow
Key Indications	Chemotherapy-induced febrile neutropaenia prevention (high-risk chemo regimens), Treatment of neutropaenia (post-chemo, congenital, drug-induced), Stem cell mobilisation (before harvesting for transplant - mobilises haematopoietic progenitors into peripheral blood)
Major Side Effects	Bone pain (most common - medullary expansion; paracetamol ± ibuprofen), Splenomegaly (↑ splenic workload; rare: splenic rupture), Elevated LDH/uric acid, Leukocytosis (excessive WBC count if overdosed)
HKMLE Paper	Paper I Medicine, Paper II Surgery

9c. Thrombopoietin Receptor Agonists (TPO-RAs)

Drug	Indication	Notes
Romiplostim	Immune thrombocytopaenia (ITP) - second-line after steroids	SC weekly; stimulates platelet production; avoid if portal hypertension (splenic sequestration)
Eltrombopag	ITP, aplastic anaemia (with ciclosporin), thrombocytopaenia in HCV/CLD	Oral; monitor LFTs; can cause hepatotoxicity; take without food and away from polyvalent cations (chelation)

Feature	Detail
Mechanism	Bind and activate thrombopoietin receptor (Mpl) → stimulate megakaryocyte proliferation → ↑ platelet production
Major Side Effects	Bone marrow reticulin fibrosis (with prolonged use), Thrombosis (↑ platelet count → VTE risk), Headache
HKMLE Paper	Paper I Medicine

10. REVERSAL AGENTS SUMMARY TABLE

Mnemonic: "4Ps + 2Is + 1A = Protamine (heparin), Phytomenadione/Vitamin K (warfarin), PCC (warfarin/Xa), Platelet transfusion, Idarucizumab (dabigatran), bIn (Andexanet alfa - Xa), Aminocaproic/TXA (fibrinolytics)"

Drug Reversed	Reversal Agent	Notes
UFH	Protamine sulfate 1mg per 100 units heparin (IV slow)	Risk of hypotension, bradycardia, anaphylaxis (especially fish allergy or prior vasectomy)
LMWH	Protamine sulfate (partial: ~60% reversal)	1mg per 1mg enoxaparin; less predictable than UFH reversal
Warfarin (non-urgent)	Vitamin K (phytomenadione) oral/IV	Slow onset (6-12h oral; 1-2h IV); IV associated with anaphylaxis risk
Warfarin (urgent/major bleed)	4-factor PCC (Beriplex) + IV Vitamin K	Faster and lower volume than FFP; contains factors II, VII, IX, X + Proteins C and S
Dabigatran	Idarucizumab (Praxbind) 5g IV	Monoclonal Ab fragment; reverses dabigatran within minutes; no anticoagulant effect
Rivaroxaban/Apixaban/Edoxaban	Andexanet alfa (recombinant Xa decoy)	Expensive; alternative = 4F-PCC 25-50 units/kg if unavailable
Fibrinolytics	TXA (Tranexamic acid) + FFP/cryoprecipitate	No specific antidote; supportive care + antifibrinolytic
Heparin-induced excess	Stop heparin; argatroban or fondaparinux (if HIT)	-

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
Warfarin INR targets (AF vs mechanical valve)	Paper I Medicine	Correct target range
Warfarin drug interactions (amiodarone → ↑INR)	Paper I Medicine	Drug interaction scenario
Warfarin in pregnancy → teratogen; use LMWH	Paper III OG	Safe drug in pregnancy
LMWH vs UFH monitoring (aPTT vs anti-Xa)	Paper I / Paper II	Monitoring parameter
HIT diagnosis and management (stop heparin, start argatroban)	Paper I / Paper II	Emergency management
HIT - platelets CONTRAINDICATED	Paper I / Paper II	Management "trap" MCQ
DOAC selection: renal failure → avoid dabigatran	Paper I Medicine	Drug selection scenario
DOAC reversal: dabigatran → idarucizumab	Paper I / Paper II	Reversal agent
DOAC reversal: Xa inhibitors → andexanet alfa	Paper I / Paper II	Reversal agent
DOACs not for mechanical heart valves	Paper I Medicine	Contraindication
Alteplase for stroke ≤4.5h (CT head first)	Paper I / Paper II	Emergency protocol
Streptokinase → antigenic, one use only	Paper I Medicine	Side effect/contraindication
TXA CRASH-2 trial: <3h trauma mortality benefit	Paper I / Paper II	Evidence-based MCQ
TXA in PPH (WOMAN trial)	Paper II / Paper III	Obstetric emergency
Iron: ferrous better absorbed, Vit C enhances	Paper I Medicine	Pharmacology
B12 IM for pernicious anaemia (not oral)	Paper I Medicine	Route of administration
Folate never alone if B12 deficiency possible (spinal cord risk)	Paper I Medicine	Clinical trap
High-risk pregnancy: 5mg folate preconception	Paper III OG	Dosing
EPO target Hb 100-120 g/L in CKD (not normal)	Paper I Medicine	Monitoring target
G-CSF: bone pain = most common side effect	Paper I Medicine	Side effect
Prasugrel contraindicated after prior stroke/TIA	Paper I Medicine	Contraindication scenario
Ticagrelor + dyspnoea = adenosine effect (not bronchospasm)	Paper I Medicine	Side effect interpretation

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
Warfarin factors blocked	"1972" = factors I (fibrinogen), IX, VII, II + Proteins C and S (actually 2, 7, 9, 10 + C + S)
Warfarin ↑ INR drugs	"CAFE MIX" = Clarithromycin/ciprofloxacin, Amiodarone, Fluconazole, Erythromycin, Metronidazole, Isoniazid, eXcretion inhibitors (statins)
Warfarin ↓ INR drugs	"PRICARS" = Phenytoin, Rifampicin, Isoniazid (high dose), Carbamazepine, Alcohol (chronic), St John's Wort
DOAC target summary	"3 Xas + 1 IIa" = rivaroxaban, apixaban, edoxaban (Xa) + dabigatran (IIa)
DOAC reversal	"I-DAR for IIa (dabigatran), AND-exanet for Xa"
HIT management	"Stop Heparin, Start Argatroban/Fondaparinux, NO platelets, NO warfarin yet"
Thrombolytics = contraindicated	"BRAIN HURTS" (Bleeding, Recent surgery, Aortic dissection, Intracranial history, Neurosurgery, Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time exceeded, Severe coagulopathy)
TXA rule	"3 hours or bust" (CRASH-2: must give within 3h of trauma)
Iron absorption tips	"Vitamin C = ↑; Tea/antacids = ↓; Ferrous > Ferric"
B12 vs folate anaemia	"B12 = Bad nerves (subacute combined degeneration); Folate = Fine nerves"
EPO target in CKD	"100-120 g/L, NOT normal" (overcorrection → VTE + CV events)
G-CSF side effect	"BONE pain" (marrow expansion)
Prasugrel contraindication	"Prior TIA/stroke = Prasugrel is PRASUREly dangerous"

Sources: Lippincott Illustrated Reviews Pharmacology; Goldman-Cecil Medicine; Roberts & Hedges' Clinical Procedures in Emergency Medicine; Tintinalli's Emergency Medicine; Rosen's Emergency Medicine; Miller's Anesthesia; Schwartz's Principles of Surgery; Creasy & Resnik's Maternal-Fetal Medicine

Give me high-yield HKMLE notes on Emergency & Toxicology Pharmacology with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - Antidotes (naloxone, flumazenil, N-acetylcysteine, activated charcoal, digoxin-specific antibodies, protamine, vitamin K, fomepizole, atropine, pralidoxime, sodium bicarbonate, calcium gluconate, hydroxocobalamin, dantrolene) - Anaphylaxis drugs (adrenaline/epinephrine, antihistamines, corticosteroids) - Sedation for intubation (ketamine, propofol, etomidate, midazolam, fentanyl, rocuronium, suxamethonium/succinylcholine) - Resuscitation drugs (adrenaline, amiodarone, atropine, calcium, magnesium, sodium bicarbonate) - Common poisonings management (paracetamol, aspirin, opioid, benzodiazepine, TCA, lithium, digoxin, theophylline, methanol/ethylene glycol, cyanide, organophosphates, carbon monoxide) Use tables where helpful. No long paragraphs. No fluff. Match the style of my Antibiotics notes.

Finding Sources

Reading File

Excellent - I have comprehensive data from Lippincott and Washington Manual. I now have everything needed to compile the full notes.

High-Yield HKMLE: Emergency & Toxicology Pharmacology Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): Toxicodromes, antidotes, poisoning management, drug overdoses

Paper II Surgery/Emergency (45 MCQs): RSI drugs, anaphylaxis management, cardiac arrest resuscitation, trauma toxicology

Paper III Paediatrics/OG (30 MCQs): Paediatric resuscitation doses, drug safety in pregnancy/lactation, paediatric poisoning

FRAMEWORK: APPROACH TO POISONING

Mnemonic: "DRIED = Decontaminate, Resuscitate, Identify toxidrome, Enhance elimination, Deliver antidote"

Step	Action
1. Resuscitate	ABC, IV access, O2, ECG, glucose
2. Decontaminate	Activated charcoal (within 1h); gastric lavage rarely used; eye/skin wash
3. Identify toxidrome	Match clinical features to syndrome (see below)
4. Enhance elimination	Haemodialysis, urine alkalinisation, multi-dose activated charcoal
5. Antidote	Specific antidote where available

MASTER TOXIDROME TABLE

Mnemonic: "SODA-C" = Sympathomimetic, Opioid, Downer (cholinergic/sedative), Anticholinergic, CNS syndromes

Toxidrome	Cause	HR	BP	Pupils	Temp	Sweating	Bowel sounds	Key Features
Sympathomimetic	Cocaine, amphetamines, MDMA	↑↑	↑↑	Dilated (mydriasis)	↑	↑↑	↑	Agitation, seizures, MI, stroke, hyperthermia
Opioid	Heroin, morphine, codeine, fentanyl	↓	↓	Pinpoint (miosis)	↓	↓	↓	Triad: coma + miosis + respiratory depression
Anticholinergic	TCAs, antihistamines, atropine, scopolamine	↑	↑	Dilated (mydriasis)	↑	Dry/hot	↓	"Mad as a hatter, hot as hell, dry as a bone, blind as a bat, red as a beet"; urinary retention, flushing, delirium
Cholinergic	Organophosphates, carbamates, nerve agents	↓	↓	Pinpoint (miosis)	-	↑↑	↑↑	SLUDGE+DUMBELS (see below), bronchospasm, seizures
Sedative/hypnotic	Benzodiazepines, barbiturates, GHB	↓	↓	Normal/small	↓	-	↓	CNS/resp depression, normal pupils (unlike opioids)
Serotonin syndrome	SSRIs ± MAOIs ± other serotonergic drugs	↑	↑	Dilated	↑↑	↑↑	↑	TRIAD: altered mental status + neuromuscular abnormalities (clonus/hyperreflexia) + autonomic instability
NMS	Antipsychotics (↓ dopamine)	↑	↑	Normal	↑↑↑	↑↑	↓	"FEVER": Fever, Encephalopathy, Vital signs unstable, Elevated CK, Rigidity (lead-pipe)

1. ACTIVATED CHARCOAL (AC)

Feature	Detail
Mechanism	Porous carbon adsorbs drugs/toxins in GI lumen → prevents absorption; does NOT enter bloodstream
Timing	Most effective within 1 hour of ingestion
Multi-dose AC	Enhances elimination of: theophylline, digoxin, phenobarbital, carbamazepine, quinine (enterohepatic recirculation/gut dialysis); requires active bowel sounds before each dose
Key Indications	Most oral drug ingestions; used within 1h
Does NOT work for	LIAP = Lithium, Iron, Alcohols (methanol, ethanol, ethylene glycol), Potassium; also lead, heavy metals, cyanide
Contraindications	Reduced GCS/unprotected airway (aspiration risk), caustic ingestion (acid/alkali), intestinal obstruction, absent bowel sounds
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: Activated charcoal does NOT work for LIAP = Lithium, Iron, Alcohols, Potassium. These require specific antidotes or dialysis.

2. ANTIDOTES MASTER TABLE

Mnemonic: "Every Poisoned Patient Needs Some Antidote Fast" - memorise each antidote-poison pair

Poison/Drug	Antidote	Mechanism of Antidote
Paracetamol	N-Acetylcysteine (NAC)	Glutathione precursor + substitute → detoxifies NAPQI
Opioids	Naloxone	Competitive opioid receptor antagonist (μ, κ, δ)
Benzodiazepines	Flumazenil	Competitive GABA-A receptor antagonist
Organophosphates	Atropine + Pralidoxime	Atropine: blocks muscarinic receptors; Pralidoxime: reactivates acetylcholinesterase
TCAs/salicylates	Sodium bicarbonate	Alkalinises blood → reduces TCA Na-channel binding; alkalinises urine → traps salicylate for excretion
Warfarin	Vitamin K + PCC	VK = cofactor for II, VII, IX, X synthesis; PCC = immediate factor replacement
Heparin	Protamine sulfate	Binds heparin ionically → neutralises anticoagulant effect
Dabigatran	Idarucizumab	Anti-dabigatran monoclonal antibody Fab
Xa inhibitors	Andexanet alfa	Recombinant Xa decoy
Digoxin	Digoxin-specific antibody fragments (Fab - DigiFab)	Bind and neutralise digoxin → renal excretion
Cyanide	Hydroxocobalamin (preferred)	Binds CN directly → cyanocobalamin (B12) formed → excreted; OR sodium nitrite + sodium thiosulfate (older kit)
Carbon monoxide	100% O2 (hyperbaric if available)	Displaces CO from haemoglobin (CO has 250x affinity vs O2; high-flow O2 speeds dissociation)
Methanol / Ethylene glycol	Fomepizole (preferred) or ethanol	Inhibits alcohol dehydrogenase → prevents formation of toxic metabolites (formic acid / oxalic acid)
Beta-blocker OD	High-dose insulin (HIT), atropine, glucagon	Glucagon: stimulates cAMP independently of β-receptor; HIT: improves myocardial glucose uptake
Calcium channel blocker OD	High-dose insulin (HIT) + calcium gluconate + lipid emulsion	HIT = vasopressor for CCB OD; calcium gluconate: restores extracellular calcium; lipid emulsion: "lipid sink" trapping fat-soluble drug
Iron	Deferoxamine	Chelates free iron → excreted in urine
Lead	DMSA (succimer) or EDTA	Chelates lead
Methotrexate	Leucovorin (folinic acid)	Bypasses DHFR blockade → provides active folate
Serotonin syndrome	Cyproheptadine	5-HT2A antagonist
NMS	Dantrolene (if severe) + bromocriptine	Dantrolene: blocks ryanodine receptor → ↓ Ca2+ release → relaxes skeletal muscle; bromocriptine: D2 agonist
Malignant hyperthermia	Dantrolene	Same as above
Hyperkalemia (cardiac)	Calcium gluconate	Membrane stabilisation (does not lower K+)
Hydrofluoric acid	Calcium gluconate	Chelates fluoride ions

3. ANTIDOTES - INDIVIDUAL DRUG DETAILS

3a. Naloxone

Feature	Detail
Mechanism	Competitive μ-opioid receptor antagonist (also κ and δ) → reverses opioid-induced CNS/respiratory depression
Key Indications	Opioid overdose (heroin, morphine, fentanyl, codeine, tramadol), respiratory depression from opioid analgesia; can partially reverse clonidine toxicity
Route/Dose	IV (0.4-2mg), IM, intranasal, ET; repeat every 2-3 min PRN; short t½ (~1h) → must monitor for re-narcotisation with long-acting opioids (e.g., methadone) → infusion may be needed
Major Side Effects	Precipitates opioid withdrawal (agitation, vomiting, tachycardia, hypertension, pulmonary oedema) if given in excess; use titrated doses - give enough to restore breathing, not full reversal
Contraindications	None absolute in overdose setting
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearls:

Opioid triad: Coma + Miosis + Respiratory depression → naloxone

Give enough to restore breathing, NOT full consciousness (avoid precipitating withdrawal)

Fentanyl overdose may require high doses due to potency; naloxone t½ shorter than most opioids → infusion needed

3b. Flumazenil

Feature	Detail
Mechanism	Competitive GABA-A receptor antagonist at benzodiazepine binding site → reverses BZD-induced sedation/coma
Key Indications	Benzodiazepine overdose (especially if airway compromise), reversal of procedural sedation
Route/Dose	IV 0.2mg increments (up to 1-3mg); short t½ (1h) → resedation can occur - repeat doses or infusion may be needed
Major Side Effects	Precipitates seizures (in BZD-dependent patients or mixed TCA+BZD OD), acute withdrawal in BZD-dependent patients, anxiety, nausea
Contraindications	Known or suspected TCA overdose (removes BZD protection against seizures → fatal status epilepticus); BZD-dependent patients (seizure risk); head injury; raised ICP
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: NEVER give flumazenil in suspected TCA overdose - removing BZD sedation unmasks TCA-induced seizures that may be fatal. This is a classic HKMLE trap question.

3c. N-Acetylcysteine (NAC)

Feature	Detail
Mechanism	Glutathione precursor and substitute → replenishes hepatic glutathione → detoxifies NAPQI (toxic paracetamol metabolite); also acts as antioxidant
Key Indications	Paracetamol overdose; most effective if started within 8-10 hours; still give even if >10h (hepatic failure risk reduction)
How to use	Plot serum paracetamol level against time on Rumack-Matthew nomogram (level must be measured at ≥4h post-ingestion); if above treatment line → start NAC IV
Route	IV preferred (3-bag regimen: 150mg/kg over 1h, then 50mg/kg over 4h, then 100mg/kg over 16h); also oral
Major Side Effects	Anaphylactoid reaction (urticaria, flushing, bronchospasm - NOT IgE mediated; treat with antihistamine + slow infusion rate; do NOT stop NAC permanently), Nausea/vomiting
Contraindications	No absolute contraindications in overdose setting
HKMLE Paper	Paper I Medicine, Paper II, Paper III

HKMLE Pearl: Nomogram-guided treatment - cannot use nomogram for staggered overdose (multiple doses over time) → treat empirically if >75mg/kg ingested or if unsure of timing.

3d. Fomepizole

Feature	Detail
Mechanism	Inhibits alcohol dehydrogenase → blocks metabolism of methanol/ethylene glycol to toxic metabolites (formic acid and oxalic/glycolic acid)
Key Indications	Methanol poisoning, Ethylene glycol poisoning; must give early (before metabolites accumulate)
Alternative	Ethanol IV/oral (also inhibits ADH; cheaper but more difficult to titrate, causes intoxication)
Adjunct	Haemodialysis for severe acidosis, high levels, visual symptoms (methanol), renal failure (ethylene glycol)
HKMLE Paper	Paper I Medicine, Paper II

3e. Atropine + Pralidoxime (Organophosphate antidotes)

Mnemonic: "ATROPINE = Anticholinergic Treatment; PRALIDOXIME = reactivates cholinesterase before ageing"

Feature	Detail
Organophosphate mechanism of toxicity	Irreversibly inhibit acetylcholinesterase → ACh accumulates at all synapses → muscarinic + nicotinic + CNS effects
Cholinergic toxidrome: SLUDGE	Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis
Cholinergic toxidrome: DUMBELS	Diarrhoea, Urination, Miosis, Bradycardia/bronchospasm, Emesis, Lacrimation, Salivation/secretions
Nicotinic effects	Muscle fasciculations → paralysis (including respiratory muscles), tachycardia (can mask bradycardia)
CNS effects	Seizures, coma

Drug	Mechanism	Use	Dose/Notes
Atropine	Competitive muscarinic receptor antagonist → blocks SLUDGE effects	First-line; treat muscarinic effects (secretions, bronchospasm, bradycardia); give large doses - titrate to drying of secretions (not pupil size or HR)	Start 2-4mg IV, double every 5-10min; may need 100+ mg in severe poisoning; endpoint = dry secretions + clear chest
Pralidoxime (2-PAM)	Reactivates acetylcholinesterase before irreversible "ageing" → restores enzyme function → treats nicotinic effects (weakness, paralysis)	Adjunct to atropine; treat nicotinic/CNS effects; must be given EARLY before ageing (organophosphate permanently bonds to AChE after hours)	Give within hours of exposure; less effective in carbamate poisoning (reversible anyway)

HKMLE Pearls:

Atropine titrated to secretions (NOT to heart rate) - the classic exam distinction

Pralidoxime only works before "ageing" (irreversible covalent bonding of OP to AChE) - use early

Carbamates (e.g., physostigmine): cause cholinergic syndrome but reversible spontaneously → atropine yes, pralidoxime NOT needed (and may be harmful)

3f. Sodium Bicarbonate

Feature	Detail
Mechanism	Alkalinises blood (serum pH ↑) → reduces TCA binding to Na+ channels (ion-trapping); alkalinises urine (urine pH ↑ to 7.5-8) → traps ionised salicylate/phenobarbital in tubular lumen → ↑ renal elimination
Key Indications (toxicology)	TCA overdose (QRS widening >120ms or arrhythmia → give NaHCO3 to target pH 7.45-7.55); Salicylate poisoning (urinary alkalinisation); Hyperkalaemia (shifts K+ intracellularly); Severe metabolic acidosis in cardiac arrest
In Cardiac Arrest	NaHCO3 given for: hyperkalaemia-induced arrest, TCA-induced arrest, prolonged arrest with severe acidosis
Major Side Effects	Hypernatraemia, hypokalaemia (alkalosis shifts K+ intracellular), paradoxical CNS acidosis (CO2 crosses BBB), volume overload
Contraindications	Metabolic alkalosis, Respiratory acidosis (worsens CO2 retention)
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: TCA OD + wide QRS (>120ms) = sodium bicarbonate IV (narrows QRS and prevents VT/VF). Also give for TCA-induced hypotension unresponsive to fluids. Target serum pH 7.45-7.55.

3g. Calcium Gluconate / Calcium Chloride

Feature	Detail
Mechanism	Restores extracellular calcium → stabilises myocardial cell membrane (does NOT lower K+ - purely membrane stabilising)
Key Indications	Hyperkalaemia (peaked T waves, widened QRS, sine wave → calcium FIRST for cardiac protection); Calcium channel blocker OD (restores Ca2+ signalling); Hypocalcaemia; Hydrofluoric acid burns (chelates fluoride); Hypermagnesaemia
Route	IV (calcium gluconate = safer peripherally; calcium chloride = more elemental Ca2+ - central line preferred)
Side Effects	Bradycardia if given too rapidly; tissue necrosis if extravasation of calcium chloride; raises digoxin toxicity (hypercalcaemia potentiates digoxin)
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: In hyperkalaemia - "C-BIG-K-Drop": Calcium (stabilise heart), Bicarbonate, Insulin + Glucose, Kayexalate (remove K+), Dialysis (definitive)

3h. Hydroxocobalamin

Feature	Detail
Mechanism	Binds cyanide directly → forms cyanocobalamin (vitamin B12) → renally excreted; non-toxic
Key Indications	Cyanide poisoning (fire/smoke inhalation - especially house fires with plastics/synthetics; industrial/laboratory exposure; suicidal ingestion)
Dose	5g IV over 15 minutes; may repeat once
Major Side Effects	Transient hypertension, tachycardia; red/pink discolouration of skin and body fluids (important: interferes with pulse oximetry and colorimetric lab tests)
Alternative antidote	Sodium nitrite + sodium thiosulfate (older kit; less preferred - induces methemoglobinaemia which is dangerous in CO+CN co-exposure)
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: Hydroxocobalamin = preferred cyanide antidote in smoke inhalation (co-existing CO poisoning makes methemoglobin induction dangerous). Classic scenario: firefighter/house fire victim with severe lactic acidosis, haemodynamic instability, "cherry red" skin (or not red if CO predominates).

3i. Dantrolene

Feature	Detail
Mechanism	Blocks ryanodine receptor in sarcoplasmic reticulum → inhibits Ca2+ release → reduces skeletal muscle contraction/rigidity
Key Indications	Malignant hyperthermia (MH) (triggered by volatile anaesthetics + suxamethonium); NMS (neuroleptic malignant syndrome) if severe
Dose	MH: 2.5mg/kg IV bolus, repeat every 5 min up to 10mg/kg total; then maintenance
Major Side Effects	Muscle weakness, hepatotoxicity (chronic oral use)
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: Malignant Hyperthermia (MH) vs NMS:

MH: Triggered by suxamethonium/volatile anaesthetics; onset minutes in OR; extreme hyperthermia, muscle rigidity, masseter spasm, metabolic acidosis, ↑ CO2; → stop trigger + dantrolene immediately

NMS: Triggered by antipsychotics (dopamine blockade); onset hours-days; hyperthermia, rigidity, ↓ consciousness, ↑ CK; → stop antipsychotic + supportive + dantrolene ± bromocriptine

3j. Digoxin-Specific Fab Antibodies (DigiFab)

Feature	Detail
Mechanism	Antibody fragments bind free digoxin → inactive complex → renally excreted
Key Indications	Severe digoxin toxicity: life-threatening arrhythmias (VT, VF, complete heart block, asystole), severe bradycardia unresponsive to atropine, digoxin level >10 ng/mL, acute ingestion >10mg (adults)
Digoxin toxicity features	GI: nausea, vomiting, diarrhoea; Visual: yellow-green halos (xanthopsia), blurred vision; Cardiac: any arrhythmia (most common = bradycardia + heart block; also AF with slow ventricular response; VT/VF with hypokalaemia); Bigeminy/trigeminy
Toxicity risk factors	Hypokalaemia (most important - K+ competes with digoxin for Na/K-ATPase binding), Hypomagnesaemia, Hypercalcaemia, Hypothyroidism, Renal impairment
Management of digoxin toxicity	Correct hypokalaemia (KCl), Correct hypomagnesaemia; Atropine for bradycardia; DigiFab for life-threatening toxicity; AVOID calcium (worsens digoxin toxicity)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Hypokalaemia potentiates digoxin toxicity → always check K+ in digoxin toxicity

Calcium is CONTRAINDICATED in digoxin toxicity (hypercalcaemia → same effect as digoxin → worsens toxicity; "stone heart")

Digoxin toxicity can cause bidirectional VT (pathognomonic)

4. SPECIFIC POISONING MANAGEMENT

4a. Paracetamol Overdose

Phase	Time	Features
Phase 1	0-24h	Nausea, vomiting, malaise (may be asymptomatic)
Phase 2	24-72h	RUQ pain, ↑ ALT/AST, rising INR/PT
Phase 3	72-96h	Peak hepatotoxicity, jaundice, coagulopathy, renal failure, hepatic encephalopathy
Phase 4	4 days-2 weeks	Recovery (or death from liver failure)

Management	Detail
Serum paracetamol level	Measure at ≥4h post-ingestion; plot on Rumack-Matthew nomogram
Activated charcoal	If within 1h of ingestion
N-Acetylcysteine (NAC)	If above treatment line on nomogram; start within 8-10h (still give if late); IV 3-bag regimen
Liver transplant assessment	King's College Criteria: pH <7.3; OR PT >100s + Creatinine >300 µmol/L + Grade III-IV encephalopathy

4b. Salicylate (Aspirin) Overdose

Mnemonic: "SALE" = Salicylates cause Acidosis (metabolic) + Lungs (NCPE) + Ears (tinnitus) + Early alkalosis (resp)

Feature	Detail
Mechanism of toxicity	Uncouples oxidative phosphorylation → ↑ O2 consumption + CO2 production → respiratory alkalosis initially (direct stimulation of respiratory centre) then metabolic acidosis (lactic acid + salicylate itself) → mixed picture
Clinical features	Tinnitus/deafness, nausea/vomiting, hyperventilation, sweating, hyperthermia, mixed resp alkalosis + metabolic acidosis on ABG, non-cardiogenic pulmonary oedema (severe), altered consciousness (late = severe)
Management	IV fluids, urinary alkalinisation (IV NaHCO3 to urine pH 7.5-8 → ↑ ionised salicylate trapping in urine → ↑ excretion); haemodialysis if: severe poisoning, renal failure, pulmonary oedema, neurological features, salicylate >700mg/L
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: Never give NaHCO3 to the point of severe alkalosis (serum pH >7.55) - paradoxically worsens CNS penetration. Haemodialysis = definitive treatment for severe salicylate poisoning.

4c. Opioid Overdose

Feature	Detail
Classic triad	Coma + Miosis + Respiratory depression
Management	ABC + naloxone IV/IM/intranasal titrated to restore breathing; monitor for re-narcotisation (naloxone t½ shorter than most opioids → repeat doses or infusion for long-acting opioids/methadone)
Pitfalls	Tramadol → seizures (not reversed by naloxone); fentanyl/carfentanil → very high naloxone doses needed
HKMLE Paper	Paper I Medicine, Paper II

4d. Benzodiazepine Overdose

Feature	Detail
Clinical features	CNS/respiratory depression; pupils normal or mildly small (unlike opioids: pinpoint); no fasciculations
Management	Supportive (ABC, airway management); flumazenil only if necessary (reversal of procedural sedation; rarely used in OD due to seizure risk)
Key distinction from opioids	Normal/near-normal pupils; flumazenil reversal (NOT naloxone); respiratory depression less severe unless combined
HKMLE Paper	Paper I Medicine

4e. TCA (Tricyclic Antidepressant) Overdose

Mnemonic: "TCA OD = 3 killers: Na-channel blockade (arrhythmia), Anticholinergic (tachycardia/hyperthermia), Alpha-1 blockade (hypotension)"

Feature	Detail
Mechanism of toxicity	Fast Na+ channel blockade → QRS widening → VT/VF; anticholinergic effects; alpha-1 blockade → hypotension; antihistamine → sedation; GABA-A antagonism → seizures
Clinical features	Anticholinergic features + QRS widening (>120ms = danger zone) + prolonged QTc → VT/TdP + seizures + hypotension + R wave in aVR (specific ECG sign)
ECG signs	Wide QRS (>120ms) - proportional to severity; R wave in aVR >3mm; rightward axis; prolonged QTc
Management	Sodium bicarbonate IV (target pH 7.45-7.55; narrows QRS); IV fluids for hypotension (NOT more NaHCO3 alone); Benzodiazepines for seizures; intubation if needed; Lipid emulsion (last resort)
Do NOT give	Flumazenil (precipitates fatal seizures); Physostigmine (worsens arrhythmias)
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearls:

Wide QRS = #1 ECG marker of TCA severity → sodium bicarbonate

R wave in aVR ≥3mm = highly specific for TCA poisoning

Seizures → use BZDs (diazepam/lorazepam); NOT phenytoin (worsens Na-channel blockade in TCA OD)

4f. Lithium Toxicity

Mnemonic: "LITHIUM SHAKES" = neurological features + narrow therapeutic window

Feature	Detail
Therapeutic window	0.4-1.0 mmol/L (therapeutic); >1.5 = mild toxicity; >2.0 = moderate; >2.5 = severe
Clinical features	Coarse tremor, polyuria/polydipsia (NDI - nephrogenic diabetes insipidus), hypothyroidism; Toxicity: N/V/D, ataxia, confusion, dysarthria, muscle twitching, seizures, coma, cardiac arrhythmias
Causes of toxicity	Dehydration, NSAIDs (↑ tubular reabsorption of Li), ACEi/ARBs (same), thiazide diuretics (same), salt restriction
Management	Stop lithium; IV 0.9% NaCl (↑ renal Li excretion by restoring Na balance); haemodialysis if: Li >2.5-3.0 + neurological features; activated charcoal does NOT adsorb lithium
HKMLE Paper	Paper I Medicine

4g. Digoxin Toxicity

(See antidote section 3j above for full detail)

Key Points for HKMLE
Most common arrhythmia = bradycardia + AV block
ECG "digoxin effect" (not toxicity): down-sloping ST depression ("reverse tick/hockey stick")
Toxicity: any arrhythmia; bidirectional VT = pathognomonic
Hypokalaemia = major risk factor for toxicity
Treatment: KCl + MgSO4 + DigiFab; avoid calcium

4h. Theophylline Toxicity

Feature	Detail
Clinical features	GI: severe N/V; Neuro: seizures (refractory), tremor, agitation; Cardiac: tachyarrhythmias (SVT, AF, VT), hypotension; Metabolic: hypokalaemia, hyperglycaemia, metabolic acidosis
Management	Multi-dose activated charcoal (interrupts enterohepatic recirculation); haemodialysis for severe poisoning; BZDs for seizures (NOT phenytoin); beta-blockers for tachyarrhythmias (propranolol/esmolol)
HKMLE Paper	Paper I Medicine

4i. Methanol / Ethylene Glycol Poisoning

Feature	Methanol	Ethylene Glycol
Source	Windshield washer fluid, methylated spirits	Antifreeze (sweet taste → accidental/paediatric ingestion)
Toxic metabolite	Formic acid (via formaldehyde)	Oxalic acid (via glycolic acid → precipitates as calcium oxalate)
Key features	Visual disturbance → blindness (formic acid damages optic nerve), metabolic acidosis, ↑ osmolar gap	Renal failure (oxalate crystals in tubules), metabolic acidosis, oxalate crystals in urine
ABG	Severe high anion gap metabolic acidosis	Same
Management	Fomepizole (or ethanol) to block ADH + haemodialysis if severe	Fomepizole (or ethanol) + haemodialysis + thiamine/pyridoxine (cofactors)
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: High anion gap metabolic acidosis + ↑ osmolar gap (measured - calculated osmolality) = methanol or ethylene glycol poisoning until proven otherwise.

4j. Carbon Monoxide Poisoning

Mnemonic: "CO = Cherry red lips, Confused, CO-Hb on ABG (not on pulse ox!)"

Feature	Detail
Mechanism	CO binds haemoglobin with 250x affinity vs O2 → carboxyhaemoglobin (COHb) → ↓ O2-carrying capacity + left shift of O2-Hb curve + inhibits cytochrome c oxidase (mitochondrial)
Clinical features	Headache (most common), nausea/vomiting, confusion, seizures, coma; Cherry-red skin (classic but rare in practice); cardiac arrhythmias; normal SpO2 on pulse oximetry (co-oximetry on ABG needed)
Management	Remove from source; 100% high-flow O2 via non-rebreather mask (reduces COHb t½ from 5h → 1h); Hyperbaric oxygen (reduces t½ to 20min): indications = COHb >25%, pregnant (any COHb), loss of consciousness, cardiac/neurological features
HKMLE Paper	Paper I Medicine, Paper II

HKMLE Pearl: Pulse oximetry reads COHb as oxyhaemoglobin → falsely NORMAL SpO2 in CO poisoning. Always order ABG with co-oximetry (measures COHb directly) when CO poisoning suspected.

4k. Cyanide Poisoning

Feature	Detail
Mechanism	Binds cytochrome c oxidase (complex IV) → blocks mitochondrial electron transport → cells cannot use O2 → histotoxic hypoxia → lactic acidosis
Setting	House fires (burning plastics/synthetics), industrial exposure, nitroprusside infusion (converted to CN), suicide
Clinical features	Rapid loss of consciousness, seizures, cardiovascular collapse, severe lactic acidosis (↑ lactate despite high O2), "arterialized" venous blood (high PvO2 - cells not extracting O2)
Management	Hydroxocobalamin 5g IV (preferred); 100% O2; decontamination; supportive
HKMLE Paper	Paper I Medicine, Paper II

4l. Organophosphate Poisoning

(See Atropine + Pralidoxime section 3e above)

Mnemonic: "SLUDGE + Seizures = Organophosphate; Give ATROPINE (huge doses) + PRALIDOXIME (early)"

5. ANAPHYLAXIS MANAGEMENT

Mnemonic: "SAFE = Stop trigger, Adrenaline (IM), Fluid, Extra drugs (antihistamine/steroids)"

Step	Drug	Dose	Notes
1. Adrenaline (Epinephrine)	FIRST AND MOST IMPORTANT	0.5mg IM (1:1000) into anterolateral thigh; repeat every 5 min if needed	IM preferred over IV (safer); auto-injector (EpiPen) = 0.3mg adult; 0.15mg child
2. IV fluid	0.9% NaCl	500-1000mL IV bolus (adult)	Treat distributive shock
3. H1 antihistamine	Chlorphenamine (chlorpheniramine) 10mg IM/IV	Adjunct only - does NOT treat life-threatening features	Treats urticaria/itching; NOT first-line
4. Corticosteroids	Hydrocortisone 200mg IV	Prevent biphasic reaction (delayed second phase 8-72h later)	Takes hours to work; adjunct only
5. Nebulised salbutamol	2.5-5mg nebulised	If significant bronchospasm	Adjunct to adrenaline

Adrenaline Mechanism in Anaphylaxis

Receptor	Effect
α1	Vasoconstriction → reverses hypotension and angioedema
β1	↑ HR and contractility → improves cardiac output
β2	Bronchodilation → reverses bronchospasm; ↓ mediator release from mast cells

HKMLE Pearls:

Adrenaline IM (NOT IV unless cardiac arrest) - IV adrenaline = reserved for refractory anaphylaxis by specialists only; IM = safe and effective

Antihistamines and steroids are NOT first-line for anaphylaxis - they are adjuncts

Biphasic reaction (recurrence up to 72h later) → reason for 4-6h observation after anaphylaxis; hydrocortisone may reduce risk

Patient on beta-blockers: glucagon may be needed (bypasses β-receptor blockade → ↑ cAMP)

6. RAPID SEQUENCE INTUBATION (RSI) DRUGS

Mnemonic: "RSI = 7Ps: Preparation, Preoxygenation, Pretreatment, Paralytic+sedation, Position, Place tube, Post-intubation care"

6a. Induction Agents (Sedatives for RSI)

Drug	Mechanism	Key Features	Use / Avoid
Ketamine	NMDA receptor antagonist → dissociative anaesthesia	↑ BP, ↑ HR (sympathomimetic); bronchodilator (↑ catecholamines); preserves airway reflexes partially; emergence reactions (hallucinations - co-prescribe BZD); does NOT suppress respiration significantly	Best for: haemodynamically unstable, reactive airways disease (asthma), trauma; Avoid: severe hypertension, raised ICP (controversial - evidence suggests safe in practice), eclampsia
Propofol	GABA-A potentiation	Rapid onset/offset; causes hypotension (vasodilation + ↓ CO); anticonvulsant; anti-emetic	Best for: elective RSI, ICU sedation, status epilepticus; Avoid: haemodynamic instability, soy/egg allergy, Propofol Infusion Syndrome (high dose/prolonged: lactic acidosis + multi-organ failure)
Etomidate	GABA-A potentiation (imidazole)	Most haemodynamically stable induction agent; rapid onset; suppresses adrenal cortex (↓ cortisol) for 24-48h (single dose); no analgesia	Best for: haemodynamically unstable patients, IHD, elderly; Avoid (relative): sepsis (adrenal suppression concern - controversial), adrenal insufficiency
Midazolam	GABA-A positive allosteric modulator	Sedation, anxiolysis, anterograde amnesia; causes hypotension; slower onset than propofol	RSI adjunct, procedural sedation, status epilepticus (IV/IM/buccal), pre-medication
Fentanyl	μ-opioid receptor agonist	Pre-RSI analgesia (attenuates intubation response - ↓ ICP surge, ↓ tachycardia/hypertension); chest wall rigidity at high doses	Pre-treatment in raised ICP, cardiovascular disease; cautious in haemodynamic instability

6b. Neuromuscular Blocking Agents (Paralytics)

Drug	Class	Onset	Duration	Key Features	Avoid
Suxamethonium (Succinylcholine)	Depolarising NMB	60-90 seconds (fastest)	10-15 minutes (short)	Standard RSI paralytic; causes fasciculations; ↑ serum K+ (can be fatal); malignant hyperthermia trigger; can use in full stomach/aspiration risk	Hyperkalaemia (burns, crush injury, denervation, prolonged immobility), pseudocholinesterase deficiency (prolonged block), personal/family history of MH, open eye injury
Rocuronium	Non-depolarising NMB	60-90 seconds (at 1.2mg/kg)	45-70 minutes (long)	Preferred alternative to suxamethonium especially when sux contraindicated; reversible with sugammadex (can't reverse suxamethonium); no K+ rise, no MH risk	None significant
Sugammadex	Selective relaxant binding agent	-	-	Reverses rocuronium (and vecuronium) immediately; encapsulates drug → excreted renally; revolutionary for "can't intubate, can't oxygenate" emergency	Renal impairment (use with caution); may cause hypersensitivity

HKMLE Pearls:

Suxamethonium + hyperkalaemia = fatal VF; contraindicated in burns (after 24h), crush injury, prolonged immobilisation, denervating conditions (spinal cord injury, stroke, Guillain-Barré)

Malignant hyperthermia = suxamethonium + volatile anaesthetics → treat with dantrolene

Rocuronium + sugammadex = now preferred RSI combination at many centres (avoids MH + K+ risks)

Etomidate = go-to for haemodynamically unstable RSI; ketamine for asthma/bronchospasm

"Cannot intubate, cannot oxygenate" → give sugammadex to reverse rocuronium and wake up patient

7. CARDIAC ARREST RESUSCITATION DRUGS

(ALS Algorithm context)

Mnemonic: "AAA + MCS" = Adrenaline x2 (shockable + non-shockable), Amiodarone, Magnesium, Calcium, Sodium bicarb

Drug	Indication in Arrest	Mechanism	Dose	Notes
Adrenaline (epinephrine)	ALL cardiac arrest rhythms (VF/VT and PEA/asystole)	α1: vasoconstriction → ↑ coronary and cerebral perfusion pressure during CPR; β1: ↑ contractility (may restart heart)	1mg IV every 3-5 minutes; in PEA/asystole: ASAP; in VF/VT: after 3rd shock	PARAMEDIC2 trial: ↑ ROSC and survival to hospital but no improvement in neurological outcome (30-day)
Amiodarone	Refractory VF/pVT (after ≥3 shocks)	Class III antiarrhythmic; multiple channel effects → ↓ VF threshold	300mg IV bolus after 3rd shock; 150mg after 5th shock	Can cause hypotension post-ROSC; do not delay defibrillation
Lidocaine	Alternative to amiodarone in VF/VT	Na+ channel blocker	100mg IV	Use if amiodarone unavailable
Atropine	Removed from ALS algorithm for asystole/PEA (no longer recommended routinely)	Muscarinic antagonist → ↑ HR	0.5-1mg IV	Still used for symptomatic bradycardia outside arrest
Calcium gluconate	PEA from hyperkalaemia, hypocalcaemia, CCB OD, hypermagnesaemia	Membrane stabilisation	10mL of 10% calcium gluconate IV	Do NOT give calcium in digoxin toxicity
Sodium bicarbonate	Hyperkalaemic arrest, TCA arrest, prolonged arrest (>10-15 min) with severe acidosis	Alkalinisation → shifts K+ + reduces TCA channel binding	50mmol (50mL of 8.4%) IV	Not routine in arrest; risk of worsening outcome if used empirically
Magnesium sulfate	Torsades de Pointes (TdP), hypomagnesaemia, digoxin toxicity	↓ Ca2+ entry; stabilises cardiac membranes	2g (8mmol) IV over 15 min (TdP); faster if in arrest	Drug of choice for TdP; also for eclampsia

4Hs and 4Ts - Reversible Causes in Cardiac Arrest

Mnemonic: "4H4T"

4Hs	4Ts
Hypoxia	Thrombosis (PE or MI)
Hypovolaemia	Tension pneumothorax
Hypo/hyperkalaemia + metabolic	Tamponade (cardiac)
Hypothermia	Toxins (drug OD/poisoning)

8. HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
Opioid triad + naloxone (titrated dose)	Paper I / Paper II	Emergency management
Flumazenil contraindicated in TCA+BZD OD	Paper I / Paper II	Contraindication TRAP
NAC for paracetamol OD (Rumack-Matthew)	Paper I / Paper II / Paper III	Protocol + timing
Fomepizole for methanol/EG (high anion gap + osmol gap)	Paper I / Paper II	Diagnosis + treatment
Hydroxocobalamin for CN poisoning (house fire)	Paper I / Paper II	Antidote identification
Organophosphate: SLUDGE + atropine to dry secretions	Paper I / Paper II	Toxidrome + treatment endpoint
Pralidoxime: must give early (before ageing)	Paper I Medicine	Mechanism-based MCQ
TCA OD: wide QRS → sodium bicarbonate	Paper I / Paper II	ECG + treatment
TCA OD: NEVER flumazenil	Paper I / Paper II	Contraindication TRAP
Digoxin toxicity: avoid calcium; give KCl + DigiFab	Paper I Medicine	Management trap
Lithium toxicity: NSAID/ACEi ↑ levels; hamodialysis	Paper I Medicine	Drug interaction + treatment
CO poisoning: normal SpO2 but high COHb	Paper I / Paper II	Investigation trap
CO: hyperbaric O2 indications (>25% COHb, pregnancy, LOC)	Paper I / Paper II	Indication criteria
Anaphylaxis: IM adrenaline FIRST (not antihistamine)	Paper I / Paper II / Paper III	Priority of management
RSI: suxamethonium contraindicated in hyperkalaemia/burns	Paper II Surgery	Contraindication scenario
RSI: malignant hyperthermia → dantrolene	Paper II Surgery	Emergency identification
RSI: rocuronium reversed by sugammadex (not neostigmine)	Paper II Surgery	Reversal agent
Ketamine: preferred for asthma/haemodynamic instability	Paper II Surgery	Drug selection
Cardiac arrest: adrenaline every 3-5 min; amiodarone after 3rd shock	Paper II Surgery	ALS protocol
Torsades de pointes → magnesium sulfate	Paper I / Paper II	Arrhythmia treatment
Activated charcoal: NOT for Li/Fe/Alcohols/K+	Paper I / Paper II	Contraindication
Hemodialysis indications: Li, methanol, EG, salicylate, theophylline	Paper I / Paper II	Elimination enhancement

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
Antidote pairs	"NAC = N-Acetyl-Cure for paracetamol"
Activated charcoal fails	"LIAP" = Lithium, Iron, Alcohols, Potassium
Organophosphate symptoms	"SLUDGE" = Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis
Anticholinergic features	"Hot, Mad, Dry, Blind, Red" (hyperthermic, delirious, dry skin, mydriasis, flushed)
Atropine endpoint in OP poisoning	Dry secretions (NOT pupil size or heart rate)
TCA OD ECG + treatment	"Wide QRS → NaHCO3"; "R in aVR ≥3mm = TCA"
Flumazenil NEVER in	"TCA + BZD OD = seizures if flumazenil"
Digoxin toxicity management	"K up, Mg up, Ca down, DigiFab for life-threatening"
CO poisoning trap	"Pulse ox LIES in CO → need ABG co-oximetry"
Anaphylaxis priority	"Adrenaline IM FIRST, antihistamine is LAST"
RSI agents	"Haemodynamic instability = Etomidate; Asthma = Ketamine; ICU = Propofol"
Suxamethonium contraindications	"BUCKS" = Burns (after 24h), Uraemia, Crush injury, K+ high, Spinal cord/denervation"
Malignant hyperthermia	"STOP sux/volatile → DANTROLENE"
Cardiac arrest drugs	"1mg Adrenaline every 3-5min; 300mg Amiodarone after 3rd shock"
Torsades →	"Magnesium 2g IV"
4H4T reversible causes	"Hypoxia, Hypovolaemia, Hypo/hyperK+, Hypothermia + Tension, Tamponade, Thrombus, Toxins"

Sources: Lippincott Illustrated Reviews Pharmacology; The Washington Manual of Medical Therapeutics; Goldman-Cecil Medicine; Tintinalli's Emergency Medicine; Rosen's Emergency Medicine; Katzung's Basic and Clinical Pharmacology 16th Edition; Miller's Anesthesia; Schwartz's Principles of Surgery

Give me high-yield HKMLE notes on Renal Pharmacology (Non-Diuretic) with mnemonics, in an easy-to-read format. Include only what is necessary for HKMLE. Do not add extra details unless they are clinically important for the exam. For each drug or drug class, tell me: 1. Mechanism (simple) 2. Key indications (HKMLE-relevant) 3. Major side effects (exam-tested) 4. Contraindications (if any) 5. Where this topic appears in HKMLE (Paper I, II, or III) Cover all essential HKMLE topics including: - Phosphate binders (calcium acetate, sevelamer, lanthanum) - Erythropoiesis-stimulating agents (erythropoietin/EPO, darbepoetin) - Iron supplementation (IV iron: ferric carboxymaltose, iron sucrose; oral iron) - Drugs for gout (allopurinol, febuxostat, colchicine) — only if not fully covered in Rheumatology - Potassium binders (patiromer, sodium zirconium cyclosilicate, calcium resonium) - Vitamin D analogues (calcitriol, paricalcitol, doxercalciferol) for renal osteodystrophy - Cinacalcet (calcimimetic) for secondary hyperparathyroidism - Sodium bicarbonate for metabolic acidosis in CKD Use tables where helpful. No long paragraphs. No fluff. Match the style of my Antibiotics notes.

Finding Sources

Reading File

I now have sufficient data from Comprehensive Clinical Nephrology, NKF Primer, Katzung's, and Harrison's. Let me compile the complete notes.

High-Yield HKMLE: Renal Pharmacology (Non-Diuretic) Notes

HKMLE Paper Mapping:

Paper I Medicine (60 MCQs): CKD complications management, anaemia of CKD, CKD-MBD, hyperkalaemia treatment, metabolic acidosis in CKD

Paper II Surgery/Emergency (45 MCQs): Perioperative drug management in CKD, acute hyperkalaemia, AKI drug management

Paper III Paediatrics/OG (30 MCQs): Renal disease in pregnancy, EPO in paediatric CKD, drug safety in CKD/pregnancy

MASTER FRAMEWORK: CKD COMPLICATIONS AND THEIR DRUGS

Mnemonic: "ABCDE of CKD complications = Anaemia, Bone disease (MBD), Calcification, Diet/Dietary phosphate, Electrolyte (K+/HCO3-)"

CKD Complication	Drug Treatment
Anaemia	EPO/darbepoetin + IV/oral iron
Hyperphosphataemia	Phosphate binders (sevelamer, calcium acetate, lanthanum)
Secondary hyperparathyroidism	Vitamin D analogues (calcitriol, paricalcitol) + Cinacalcet
Hyperkalaemia	Potassium binders (patiromer, SZC, calcium resonium)
Metabolic acidosis	Sodium bicarbonate (oral)
Renal osteodystrophy	Vitamin D analogues + phosphate control

1. ERYTHROPOIESIS-STIMULATING AGENTS (ESAs)

Mnemonic: "EPO = Every Patient On dialysis needs it (but not too much - target 100-120)"

ESA Comparison Table

Drug	Type	Half-life	Dosing Frequency
Epoetin alfa/beta	Recombinant human EPO	~8-12h IV; ~24h SC	2-3x weekly (SC preferred)
Darbepoetin alfa	Hyperglycosylated EPO analogue	~48h SC	Weekly or fortnightly
Methoxy PEG-epoetin beta (Mircera)	Continuous erythropoietin receptor activator	~130h	Monthly

Feature	Detail
Mechanism	Binds erythropoietin receptor on erythroid progenitors in bone marrow → stimulates RBC proliferation, differentiation, and survival
Key Indications	Anaemia of CKD (primary indication); chemotherapy-induced anaemia; myelodysplastic syndrome (low-risk); pre-surgical autologous blood donation
Target Hb	100-120 g/L (do NOT target normal Hb) - KDIGO recommendation
Major Side Effects	Hypertension (most common; ↑ Hb → ↑ blood viscosity → ↑ peripheral resistance), Thrombotic events (VTE, AV fistula thrombosis, stroke - especially if Hb overcorrected), Pure red cell aplasia (PRCA) (rare: anti-EPO neutralising antibodies → profound anaemia; stop ESA, switch to transfusions), Flu-like symptoms, Headache
Contraindications	Uncontrolled hypertension, Active/recent malignancy (especially haematological), PRCA (history of anti-EPO antibodies)
Before starting ESA	Always check and replete iron first (ferritin, TSAT - iron deficiency is the most common cause of ESA hyporesponsiveness)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Target Hb = 100-120 g/L in CKD - CHOIR and CREATE trials showed targeting normal Hb (130-150 g/L) → ↑ VTE + CV mortality

Iron deficiency = #1 cause of ESA hyporesponsiveness - check ferritin/TSAT before increasing ESA dose

PRCA = sudden failure to respond + severe anaemia → check anti-EPO antibodies; stop ESA immediately; do NOT switch to different ESA (cross-reacts)

AV fistula thrombosis = important complication in dialysis patients on ESA

2. IRON SUPPLEMENTATION IN CKD

Mnemonic: "IV iron for dialysis patients; Oral iron for pre-dialysis and non-dialysis CKD"

Comparison: Oral vs IV Iron

Feature	Oral Iron	IV Iron
Preparations	Ferrous sulfate 200mg TDS	Ferric carboxymaltose, Iron sucrose, Iron dextran
Absorption	10-15% (reduced by food, antacids, PPIs, inflammation)	100% (direct IV delivery)
Monitoring	Ferritin + TSAT monthly initially	Ferritin + TSAT before each dose
Preferred in	Pre-dialysis CKD (stages 1-3), mild deficiency	Haemodialysis patients (preferred - oral poorly absorbed; given via dialysis circuit); severe deficiency; oral intolerance
Key Side Effects	Constipation, nausea, dark stools, poor GI tolerance	Infusion reactions (anaphylaxis - rare with newer agents; more common with iron dextran); transient hypophosphataemia (ferric carboxymaltose - significant, check phosphate post-infusion)

IV Iron Preparations

Drug	Notes
Ferric carboxymaltose	High-dose single infusion (up to 1000mg); risk of hypophosphataemia (clinically significant; may need phosphate supplementation)
Iron sucrose	Multiple smaller doses; lower anaphylaxis risk; commonly used in dialysis unit
Iron dextran (LMW)	Test dose required (higher anaphylaxis risk than others); complete dose in one infusion

Target Iron Indices in CKD

Parameter	Target (CKD on ESA)
Ferritin	200-500 µg/L (dialysis patients); >100 µg/L (pre-dialysis)
Transferrin saturation (TSAT)	>20%

HKMLE Pearls:

Ferric carboxymaltose → hypophosphataemia (FGF23 mediated phosphaturia) - check phosphate 4-8 weeks post-infusion, especially in CKD/dialysis patients who are already phosphate-restricted

IV iron preferred in HD patients: given directly into dialysis circuit; avoids GI side effects; more reliably absorbed

Never give iron when ferritin >500 µg/L or TSAT >30% (iron overload risk)

3. PHOSPHATE BINDERS

Mnemonic: "SeLa-Ca controls phosphate: Sevelamer, Lanthanum, Calcium acetate"

Why control phosphate in CKD?

Hyperphosphataemia in CKD → ↑ FGF23 → ↓ Vitamin D activation → ↑ PTH → secondary hyperparathyroidism + vascular calcification + ↑ cardiovascular mortality

Phosphate Binder Comparison Table

Drug	Class	Mechanism	Key Features	Side Effects
Calcium acetate (PhosLo)	Calcium-based	Binds dietary phosphate in gut → insoluble Ca-phosphate complex → excreted in faeces	Cheap; also provides calcium supplementation	Hypercalcaemia (monitor Ca2+); risk of vascular calcification with long-term use; avoid if hypercalcaemia or calcification present
Calcium carbonate	Calcium-based	Same as calcium acetate	Common OTC antacid; also used as phosphate binder	Same as calcium acetate; less effective binder
Sevelamer HCl / Sevelamer carbonate (Renagel/Renvela)	Non-calcium polymer	Anion exchange resin → binds phosphate ions in gut	Non-calcium → no hypercalcaemia; also ↓ LDL cholesterol; sevelamer carbonate preferred (less acidosis than HCl form)	GI side effects (N/V, constipation); does not provide calcium; pill burden (large tablets, multiple per meal)
Lanthanum carbonate (Fosrenol)	Non-calcium	Lanthanum ions bind phosphate → lanthanum phosphate → excreted	Chewable tablet (taken with meals); non-calcium; effective	GI side effects (N/V, diarrhoea); long-term tissue accumulation of lanthanum (clinical significance uncertain)
Aluminium hydroxide	Aluminium-based	Binds phosphate	Very effective; cheap	Aluminium toxicity (encephalopathy, adynamic bone disease) with prolonged use; only use short-term (acute hyperphosphataemia); largely abandoned for chronic use
Sucroferric oxyhydroxide (Velphoro)	Iron-based	Iron binds phosphate	Non-calcium; lower pill burden	GI side effects; stains teeth

HKMLE High-Yield Points on Phosphate Binders

Phosphate Binder	HKMLE Pearl
Sevelamer	KDIGO-preferred non-calcium binder; ↓ vascular calcification risk vs calcium-based; also lowers LDL
Calcium acetate/carbonate	Avoid if hypercalcaemia or severe vascular calcification; monitor serum calcium
Aluminium hydroxide	Aluminium toxicity (dementia-like syndrome + adynamic bone) with chronic use → do NOT use chronically in CKD
Lanthanum	Chewable; must be taken with meals (binds dietary phosphate in gut)

HKMLE Pearls:

Phosphate binders must be taken WITH meals (to bind dietary phosphate as it is digested)

KDIGO guidelines: prefer non-calcium binders (sevelamer, lanthanum) in patients with hypercalcaemia, calcification, or adynamic bone disease

Aluminium = historical phosphate binder → now only short-term use acceptable; aluminium encephalopathy ("dialysis dementia") was a major complication before this was known

4. VITAMIN D ANALOGUES (for CKD-MBD)

Mnemonic: "In CKD kidneys can't 1-hydroxylate → must give active (1,25) or non-calcaemic analogues"

Background: Vitamin D Metabolism in CKD

Normal: Liver (25-hydroxylation) → Kidney (1α-hydroxylation) → Calcitriol (1,25-OH Vit D) → active form In CKD: ↓ 1α-hydroxylase → ↓ calcitriol → ↓ intestinal Ca2+ absorption → ↑ PTH → secondary hyperparathyroidism → renal osteodystrophy

Vitamin D Analogue Comparison

Drug	Type	Key Features
Calcitriol (1,25-dihydroxyvitamin D3)	Active form of Vit D	Most potent; requires no renal activation; ↑ GI calcium/phosphate absorption (risk of hypercalcaemia + hyperphosphataemia)
Alfacalcidol (1α-hydroxyvitamin D3)	Active analogue (activated by liver)	Requires only hepatic activation; widely used in CKD; similar to calcitriol in practice
Paricalcitol (19-nor-1,25-OH Vit D2)	Selective Vit D receptor activator	Preferentially suppresses PTH with less hypercalcaemia/hyperphosphataemia vs calcitriol; used in secondary hyperparathyroidism in dialysis
Doxercalciferol (1α-hydroxyvitamin D2)	Requires hepatic activation	Alternative to calcitriol; used for secondary hyperparathyroidism

Feature	Detail
Mechanism	Activate vitamin D receptor (VDR) → ↑ intestinal Ca2+ and phosphate absorption + ↑ renal Ca2+ reabsorption + directly suppress PTH synthesis in parathyroid gland
Key Indications	Secondary hyperparathyroidism in CKD (↑ PTH → bone resorption, renal osteodystrophy, cardiovascular calcification), Hypocalcaemia in CKD/hypoparathyroidism
Major Side Effects	Hypercalcaemia (most important - monitor Ca2+ regularly), Hyperphosphataemia (↑ GI phosphate absorption; must control phosphate first), Adynamic bone disease (over-suppression of PTH → no bone turnover)
Contraindications	Hypercalcaemia, Severe hyperphosphataemia (must treat phosphate first - risk of metastatic calcification if Ca x P product is high)
Monitoring	Serum Ca2+, phosphate, PTH regularly
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Treat hyperphosphataemia BEFORE starting vitamin D analogues (if phosphate uncontrolled → ↑ Ca x P product → metastatic vascular calcification)

Paricalcitol = preferred over calcitriol in many dialysis units (lower risk of hypercalcaemia/hyperphosphataemia)

Alfacalcidol = widely used in HK practice (requires only hepatic 25-hydroxylation which is intact in CKD); NOT required to go through kidney

Vitamin D deficiency in non-CKD → treat with colecalciferol (Vit D3) or ergocalciferol (Vit D2) - these are the inactive forms that still require renal activation → do NOT use in advanced CKD

5. CINACALCET (Calcimimetic)

Mnemonic: "Cinacalcet = Calcimimetic = Calcium Sensor sensitised = ↓ PTH without raising Calcium"

Feature	Detail
Mechanism	Positive allosteric modulator of calcium-sensing receptor (CaSR) on parathyroid chief cells → CaSR becomes more sensitive to extracellular Ca2+ → ↓ PTH secretion; also causes ↓ serum calcium and ↓ phosphate
Key Indications	Secondary hyperparathyroidism (sHPT) in CKD patients on dialysis (not licensed in pre-dialysis CKD in most guidelines); Primary hyperparathyroidism (inoperable/unsuitable for surgery - reduces Ca2+)
Route	Oral, once daily
Major Side Effects	Hypocalcaemia (most important - monitor; dose-dependent; especially at start of therapy - risk of tetany, seizures, QTc prolongation); Nausea/vomiting (most common; dose-related; give with food to reduce); Diarrhoea
Contraindications	Hypocalcaemia (corrected Ca2+ <2.1 mmol/L - do NOT start); Avoid in pregnancy (reduced Ca2+ delivery to foetus); Severe hepatic impairment
Monitoring	Serum calcium within 1 week of starting or dose change; regular PTH; calcium + phosphate
Drug interaction	Metabolised by CYP3A4 (strong inhibitors e.g., ketoconazole, itraconazole → ↑ cinacalcet levels); also inhibits CYP2D6 (↑ levels of tamoxifen, codeine, tricyclics)
HKMLE Paper	Paper I Medicine

Cinacalcet vs Vitamin D Analogues for sHPT

Feature	Vitamin D Analogues	Cinacalcet
Effect on PTH	↓	↓
Effect on calcium	↑ (risk of hypercalcaemia)	↓ (risk of hypocalcaemia)
Effect on phosphate	↑ (worsens)	↓ (improves)
Route	Oral or IV	Oral
When preferred	Hypocalcaemia + ↑ PTH (no cinacalcet if Ca2+ low)	Normal or ↑ Ca2+ + ↑ PTH + ↑ phosphate

HKMLE Pearls:

Cinacalcet is contraindicated when calcium is low - it causes further ↓ Ca2+

Vitamin D analogues preferred when patient has low calcium + high PTH

EVOLVE trial: cinacalcet vs placebo in HD patients → ↓ composite cardiovascular endpoint but no statistically significant mortality benefit

Nausea with cinacalcet = give with food (reduces GI side effects)

6. POTASSIUM BINDERS

Mnemonic: "SaZaPa binds K+ in the gut: Sodium ZirConium, Patiromer, calcium resoniuM"

Hyperkalaemia in CKD - Context

CKD → ↓ renal K+ excretion → hyperkalaemia → most dangerous complication = cardiac arrhythmias (VF, bradycardia, asystole)

Emergency vs Maintenance Treatment

Setting	Treatment
Acute hyperkalaemia (ECG changes/K+ >6.5)	Calcium gluconate (membrane stabilise) + Insulin/glucose + NaHCO3 + Salbutamol nebulised + Dialysis if needed
Chronic hyperkalaemia prevention	Dietary K+ restriction + Potassium binders

Potassium Binder Comparison

Drug	Mechanism	Onset	Key Features	Side Effects
Calcium resonium (calcium polystyrene sulfonate)	Ion-exchange resin: exchanges Ca2+ for K+ in colon → K+ excreted in faeces	Hours-days	Available as oral powder/enema; oldest agent; rectal administration possible (enema)	Constipation (add sorbitol - but risk of colonic necrosis), Nausea; Hypercalcaemia; Rectal/colonic necrosis (rare but serious - especially if used with sorbitol in post-op patients); Should NOT be given within 3h of other oral medications
Sodium zirconium cyclosilicate (SZC; Lokelma)	Highly selective inorganic crystal traps K+ in exchange for Na+/H+ throughout GI tract	Within 1h (rapid onset)	Rapid + effective; useful in acute hyperkalaemia management; can be used in emergency setting (ePK management)	Oedema (Na+ loading → fluid retention); mild hypokalaemia risk; nausea
Patiromer (Veltassa)	Calcium sorbitol polymer → exchanges Ca2+ for K+ in distal colon	Hours (not for acute)	Maintenance therapy for chronic hyperkalaemia; convenient (once daily); does NOT cause colonic necrosis	Constipation, hypomagnasaemia (monitor Mg2+); Hypocalcaemia; Must separate from other oral drugs by ≥3h (binds other medications)

HKMLE Pearls:

Calcium resonium = classic / oldest; note the colonic necrosis risk with sorbitol (avoid in post-op bowel); rectal enema form useful if NPO

SZC (Lokelma) = fastest onset (~1h); increasingly used for subacute hyperkalaemia management (not instant like IV calcium but faster than patiromer)

Patiromer = preferred for chronic outpatient management; once daily; safer long-term than resonium; must be taken ≥3h apart from other drugs (binds and reduces absorption of other medications including levothyroxine, antibiotics)

Dietary restriction first: avoid bananas, oranges, tomatoes, potatoes, nuts, chocolate, salt substitutes (KCl-based)

Sodium loading with SZC = caution in heart failure and severe fluid overload

7. SODIUM BICARBONATE IN CKD

Mnemonic: "Bicarb in CKD = Buffer against bone breakdown + Better progression slowing"

Feature	Detail
Why needed	CKD → ↓ urinary H+ excretion + ↓ ammoniagenesis → metabolic acidosis (serum HCO3- typically 16-20 mEq/L in advanced CKD); acidosis accelerates: muscle wasting (protein catabolism), bone demineralisation (bone buffers acid), ↑ CKD progression (tubular damage), ↑ albumin loss
Mechanism	Oral NaHCO3 → absorbed → replenishes systemic bicarbonate buffer; neutralises H+ → ↓ metabolic acidosis
Key Indications	CKD stages 3-5 (pre-dialysis) with serum HCO3- <22 mEq/L; KDIGO recommend maintaining HCO3- ≥22 mEq/L
Benefits	↓ CKD progression (reduced tubulointerstitial damage), ↓ muscle wasting, ↑ nutritional status, ↓ bone demineralisation; may reduce hyperkalaemia (alkalosis shifts K+ intracellularly)
Major Side Effects	Sodium loading → fluid retention/oedema, Hypertension (↑ Na+ load), Worsening heart failure; Metabolic alkalosis if over-dosed; GI bloating, belching (CO2 formation)
Contraindications	Severe heart failure (fluid/Na+ overload), Pulmonary oedema, Metabolic alkalosis
Dose	Typically 500-1000mg oral NaHCO3 tablets 2-3x daily (guided by serum HCO3-)
HKMLE Paper	Paper I Medicine

HKMLE Pearls:

Target serum HCO3- ≥22 mEq/L in CKD (KDIGO)

Oral bicarbonate slows CKD progression - shown in de Brito-Ashurst trial (2009): ↓ rate of eGFR decline

Cannot use oral NaHCO3 in dialysis patients → acid-base corrected via dialysate bicarbonate bath

Side effect trap: sodium load → worsens hypertension/oedema → contraindicated in fluid overloaded patients

8. FINERENONE (Nonsteroidal MRA - Emerging HKMLE Topic)

Feature	Detail
Mechanism	Selective nonsteroidal mineralocorticoid receptor antagonist → blocks aldosterone-mediated renal and cardiac fibrosis/inflammation
Key Indications	Diabetic kidney disease (DKD) with CKD + albuminuria (T2DM + eGFR 25-75 + UACR ≥30 mg/g) - FIDELIO-DKD trial
Advantage over spironolactone/eplerenone	More kidney-selective; less gynaecomastia/breast tenderness; lower risk of hyperkalaemia vs spironolactone
Major Side Effects	Hyperkalaemia (monitor K+ at 4 weeks), mild ↓ eGFR initially
Contraindications	Hyperkalaemia (K+ >5.0), severe renal impairment, concurrent use with strong CYP3A4 inhibitors
HKMLE Paper	Paper I Medicine (emerging; may appear in newer papers)

9. DRUGS TO AVOID / USE WITH CAUTION IN CKD

Mnemonic: "DAMN CKD = Drugs to Avoid/reduce in Multi-organ patients with No working Kidneys"

Drug	Issue in CKD	Action
NSAIDs	↓ renal prostaglandins → ↓ GFR → AKI; sodium/water retention; hyperkalaemia	Avoid in CKD stage 3+; only use short-term with monitoring
Metformin	Accumulation → lactic acidosis	Stop if eGFR <30; reduce dose eGFR 30-45; hold before contrast media
ACEi/ARBs	↑ serum creatinine (initial drop in GFR acceptable up to 20%); hyperkalaemia	Acceptable initial ↑ creatinine ≤20%; stop if creatinine rises >30%; monitor K+
Lithium	Accumulates in CKD; NDI (nephrogenic DI) with long-term use	Dose reduce; monitor levels closely; avoid in advanced CKD
Gentamicin/Aminoglycosides	Nephrotoxic (ATN - proximal tubule); ototoxic	Avoid/minimise use; if must use, extend dosing interval; monitor levels and creatinine
Amphotericin B	Direct tubular toxicity; renal tubular acidosis	Use lipid formulation to reduce nephrotoxicity; monitor renal function closely
Contrast media (iodinated)	Contrast-induced nephropathy	Hydrate before/after; use low-osmolal contrast; hold metformin; consider N-acetylcysteine
LMWH (e.g., enoxaparin)	Renally cleared → accumulates → bleeding	Dose reduce if eGFR <30; use UFH and monitor anti-Xa level instead
Gabapentin/Pregabalin	Renally excreted → accumulation → sedation, encephalopathy	Dose reduce based on eGFR
Digoxin	Renally excreted → toxicity	Dose reduce; target lower digoxin level
Dabigatran	80% renal excretion → ↑ bleeding risk	Avoid if eGFR <30
Nitrofurantoin	Ineffective at low GFR (insufficient urinary concentration); pulmonary toxicity	Avoid if eGFR <45 (ineffective and ↑ toxicity)
Potassium-sparing diuretics	↑ Hyperkalaemia risk	Use with caution; monitor K+
Tetracyclines	Anti-anabolic → ↑ urea; nephrotoxic (except doxycycline)	Avoid (except doxycycline which is hepatically excreted)

HKMLE PAPER DISTRIBUTION SUMMARY

Topic	Paper	Question Type
ESA target Hb 100-120 g/L (not normal)	Paper I Medicine	Monitoring target
ESA hyporesponsiveness → check iron first	Paper I Medicine	Investigation before dose increase
PRCA: anti-EPO antibodies → stop ESA	Paper I Medicine	Complication identification
Ferric carboxymaltose → hypophosphataemia	Paper I Medicine	Side effect trap
IV iron preferred in HD patients	Paper I Medicine	Drug selection scenario
Calcium-based phosphate binders → hypercalcaemia/calcification	Paper I Medicine	Side effect and contraindication
Sevelamer: non-calcium binder + ↓ LDL	Paper I Medicine	Extra benefit MCQ
Aluminium hydroxide: AVOID long-term (encephalopathy)	Paper I Medicine	Historical/safety MCQ
Phosphate binders MUST be taken WITH food	Paper I Medicine	Administration instruction
Alfacalcidol/calcitriol → hypercalcaemia	Paper I Medicine	Side effect monitoring
Treat hyperphosphataemia BEFORE vitamin D analogues	Paper I Medicine	Treatment sequence MCQ
Cinacalcet → hypocalcaemia (contraindicated if Ca2+ low)	Paper I Medicine	Contraindication TRAP
Cinacalcet vs Vit D: opposite effects on Ca2+	Paper I Medicine	Mechanism comparison
SZC (Lokelma) fastest onset among K+ binders	Paper I / Paper II	Acute management selection
Calcium resonium + sorbitol → colonic necrosis (post-op)	Paper I / Paper II	Complication/contraindication
Patiromer: separate from other drugs by ≥3h	Paper I Medicine	Drug administration trap
Oral NaHCO3: target HCO3- ≥22 mEq/L in CKD	Paper I Medicine	Treatment target
Sodium bicarbonate → fluid retention (contraindicated in HF)	Paper I Medicine	Side effect + contraindication
NSAIDs → AKI in CKD (avoid in CKD3+)	Paper I / Paper II	Drug avoidance scenario
Metformin → lactic acidosis: stop if eGFR <30	Paper I Medicine	Drug safety in CKD
Nitrofurantoin ineffective + toxic if eGFR <45	Paper I Medicine	Drug selection in CKD
Aminoglycosides → nephrotoxic + ototoxic	Paper I / Paper II	Drug safety scenario

QUICK MNEMONICS CHEAT SHEET

Topic	Mnemonic
CKD complications + drugs	"ABCDE" = Anaemia (EPO+iron), Bone/MBD (VitD+cinacalcet), Calcification (phosphate binders), Diet/phosphate (binders), Electrolyte K+/HCO3- (binders/bicarb)
ESA targets	"100-120, NOT normal" (overcorrection = VTE + ↑ CV death)
ESA hyporesponsiveness	"Iron first, PRCA if antibodies"
Phosphate binders with meals	"Eat → bind → excrete" (must take WITH food)
Calcium binders vs non-calcium	"Ca binders = hypercalcaemia + calcification risk; Sevelamer = safe + ↓ LDL"
Aluminium hydroxide	"OLD and TOXIC long-term" = avoid chronic use
Cinacalcet rule	"Low Ca2+ = NO Cinacalcet (it makes it worse)"
Vitamin D rule	"High phosphate first? Fix it BEFORE vitamin D"
Potassium binders speed	"SZC fastest (1h), Patiromer hours, Resonium = days"
Patiromer interaction	"3-hour gap from ALL other oral drugs"
NaHCO3 in CKD	"Target ≥22 mEq/L; stops bone + muscle + progression"
NaHCO3 caution	"Sodium loads → avoid in HF/oedema"
Drugs to avoid in CKD	"DAMN CKD" = Diuretics (K-sparing), Aminoglycosides, Metformin (eGFR<30), NSAIDs, Contrast (prep needed), Kinase-renal drugs (dabigatran, LMWH)"

Sources: Comprehensive Clinical Nephrology 7th Edition; NKF Primer on Kidney Diseases 8th Edition; Katzung's Basic and Clinical Pharmacology 16th Edition; Harrison's Principles of Internal Medicine 22E; Lippincott Illustrated Reviews Pharmacology

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