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🧠 PHARMACOLOGY EXAM MASTER GUIDE

Simple Explanations for Every Drug Class

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PART 1: AUTONOMIC NERVOUS SYSTEM DRUGS

First, understand the 2 teams:

• Parasympathetic (rest-and-digest) - uses Acetylcholine (ACh) as its chemical messenger
• Sympathetic (fight-or-flight) - uses Norepinephrine/Epinephrine as its chemical messenger

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🟢 CHOLINERGIC DRUGS (work on ACh system)

What receptors exist?

• Muscarinic receptors - found on heart, smooth muscle, glands (remember: "M for organs")
• Nicotinic receptors - found at ganglia and muscle junctions

The SLUDGE mnemonic = what ACh does when activated:

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DIRECT-ACTING CHOLINERGIC AGONISTS (they directly activate the receptor)

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INDIRECT-ACTING CHOLINERGIC AGONISTS = Acetylcholinesterase Inhibitors

• Examples: Sarin (nerve gas), parathion (pesticide), echothiophate (glaucoma)
• They permanently inactivate the enzyme
• Treatment of organophosphate poisoning: Give Atropine (blocks muscarinic effects) + Pralidoxime (reactivates the enzyme if given early) + Benzodiazepines (for seizures)
• Pralidoxime must be given within hours before "aging" (irreversible bonding) occurs

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CHOLINERGIC ANTAGONISTS (Anticholinergics / Antimuscarinics)

• Antidote: Physostigmine (it crosses the blood-brain barrier)

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🔴 ADRENERGIC DRUGS (work on epinephrine/norepinephrine system)

Receptor types (MEMORIZE THIS):

ADRENERGIC AGONISTS

• β2 agonists: Hypokalemia (K shifts into cells), tremor, tachycardia

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ADRENERGIC ANTAGONISTS (Blockers)

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PART 2: PSYCHIATRIC DRUGS

🔵 ANTIPSYCHOTICS

Why are they used?

The 4 dopamine pathways you MUST know:

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FIRST-GENERATION (Typical) Antipsychotics

• Low potency: Chlorpromazine, Thioridazine
• High potency: Haloperidol, Fluphenazine, Pimozide

1. EPS - Extrapyramidal Symptoms (blockade of nigrostriatal pathway):
   • Acute dystonia (hours-days): Sudden painful muscle spasms, twisted neck (torticollis), eyes rolling back (oculogyric crisis)
   • Akathisia (days-weeks): Can't sit still, restlessness, fidgeting
   • Parkinsonism (weeks-months): Tremor, rigidity, shuffling gait - looks like Parkinson's
   • Tardive dyskinesia (months-years): Repetitive involuntary movements of face, lips, tongue (irreversible in many cases!)
   • Treatment of EPS: Benztropine or Diphenhydramine for acute dystonia/parkinsonism; Propranolol for akathisia; Clonazepam
2. Neuroleptic Malignant Syndrome (NMS) - EMERGENCY!
   • "FATAL FOUR": Fever (very high, >40°C), Autonomic instability (unstable BP, HR), Tremor and rigidity ("lead pipe"), Altered consciousness
   • Also: Elevated CPK (muscle breakdown), leukocytosis, myoglobinuria (kidney damage)
   • Treatment: Stop the drug immediately! Dantrolene (muscle relaxant), Bromocriptine (DA agonist), aggressive cooling, supportive care
3. Anticholinergic effects: Dry mouth, blurred vision, constipation, urinary retention
4. Antihistamine effects: Sedation, weight gain
5. α1 blockade: Orthostatic hypotension
6. QT prolongation (especially thioridazine, pimozide) → risk of Torsades de Pointes
7. Hyperprolactinemia: Gynecomastia (breast tissue in men), galactorrhea (milk production), amenorrhea, sexual dysfunction

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SECOND-GENERATION (Atypical) Antipsychotics

• Coma/CNS depression
• Clozapine: Severe neutropenia, history of drug-induced agranulocytosis
• QT-prolonging drugs with thioridazine/ziprasidone

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🟡 ANTIDEPRESSANTS

Monoamine Theory of Depression (simplified):

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CLASS 1: SSRIs (Selective Serotonin Reuptake Inhibitors)

• Sexual dysfunction (#1 complaint - decreased libido, delayed orgasm)
• GI upset - nausea, diarrhea (worst early in treatment)
• Insomnia or drowsiness
• Weight gain (especially paroxetine)
• QT prolongation (especially citalopram at high doses)
• Increased suicidal ideation in children/adolescents (BLACK BOX WARNING - monitor closely)
• SIADH (low sodium) - rare but important, especially in elderly

• Within 14 days of MAOI use (serotonin syndrome risk!)
• Fluoxetine: Long half-life (1 week), interacts with many drugs
• Paroxetine: Most anticholinergic of the SSRIs, avoid in pregnancy (heart defects)

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CLASS 2: SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Similar to SSRIs PLUS...
• Hypertension (from NE component - especially venlafaxine at high doses)
• Sweating, dry mouth

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CLASS 3: TCAs (Tricyclic Antidepressants)

• Anti-cholinergic: Dry mouth, blurred vision, urinary retention, constipation, confusion
• Anti-histamine: Sedation, weight gain
• Anti-α1: Orthostatic hypotension → falls in elderly

• Mnemonic: "Cardiotoxic, Convulsive, Comatose"
• Widened QRS on ECG (sodium channel blockade) → ventricular arrhythmias, fatal heart rhythm
• Seizures
• Sedation/coma
• Hypotension
• Anticholinergic crisis (fever, flushing, dilated pupils, tachycardia, ileus)
• Treatment: Sodium bicarbonate IV (most important! alkalinizes blood, reverses Na-channel block), activated charcoal if early, supportive care
• DO NOT give physostigmine for TCA overdose (can worsen cardiac toxicity)

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CLASS 4: MAOIs (Monoamine Oxidase Inhibitors)

1. Tyramine-containing foods (cheese, wine, beer, aged/cured meats, soy sauce) → Hypertensive crisis (severe, explosive headache, stroke, death)
   • Normally MAO breaks down tyramine from food. Block MAO = tyramine builds up = massive norepinephrine release = sky-high BP
   • "Cheese reaction"
2. Serotonergic drugs (SSRIs, SNRIs, meperidine, tramadol, triptans, dextromethorphan - cough syrup!) → Serotonin Syndrome
3. Sympathomimetics (pseudoephedrine, amphetamines) → Hypertensive crisis

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CLASS 5: Atypical Antidepressants

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☢️ SEROTONIN SYNDROME

What is it?

Causes:

• SSRI + MAOI (most dangerous)
• SSRI + Tramadol/Meperidine
• SSRI + Triptans (sumatriptan)
• SSRI + Linezolid (antibiotic with weak MAOI activity)
• SSRI + dextromethorphan (DXM, in cough syrup)
• Overdose of serotonergic drugs

Classic TRIAD (easy to remember):

1. Altered mental status - agitation, confusion, restlessness
2. Autonomic instability - fever, sweating, tachycardia, high BP, diarrhea
3. Neuromuscular abnormalities - CLONUS (rhythmic muscle jerks, especially ankle), hyperreflexia, tremor, myoclonus

Treatment of Serotonin Syndrome:

1. Stop the offending drug immediately
2. Supportive care (IV fluids, cooling)
3. Cyproheptadine (serotonin antagonist - antihistamine that blocks 5-HT)
4. Benzodiazepines for agitation/seizures
5. Severe cases: ICU, intubation, cooling blankets

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🔮 LITHIUM

What is it?

Indications:

• Bipolar disorder (acute mania + long-term prevention)
• Augmentation of antidepressants in treatment-resistant depression
• Cluster headaches (prophylaxis)

How it works (simplified):

NARROW THERAPEUTIC INDEX - lithium is toxic at levels only slightly above therapeutic

• Therapeutic level: 0.6 - 1.2 mEq/L
• Toxic level: >1.5 mEq/L (symptoms begin)
• Severely toxic: >2.0 mEq/L

Things that INCREASE lithium levels (toxicity risk):

• Thiazide diuretics, NSAIDs (massive exam question!)
• Dehydration, low-sodium diet, vomiting, diarrhea, excessive sweating
• ACE inhibitors
• Remember: "Lithium is like sodium" - when the body loses sodium, it retains lithium

Side effects (by level):

• Fine tremor (hands), mild cognitive dulling, polyuria (excessive urination), polydipsia (excessive thirst), hypothyroidism, weight gain, acne

• Coarse tremor (gets bigger), nausea, vomiting, diarrhea, ataxia (stumbling)

• Confusion, seizures, cardiac arrhythmias, stupor, coma, DEATH

Treatment of lithium toxicity:

• Stop lithium
• Aggressive IV saline (flushes lithium out)
• Hemodialysis for severe toxicity (levels >4.0 or if symptomatic)
• NO antidote exists - just support + dialysis

Other important facts:

• Lithium is renally eliminated (not metabolized by liver) → safe in liver disease, but reduce dose in kidney disease
• Ebstein anomaly - cardiac malformation risk if taken in first trimester of pregnancy → avoid in pregnancy, use valproate or lamotrigine with caution
• Monitor: Renal function, thyroid function, serum levels

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PART 3: CARDIOVASCULAR DRUGS

💊 ACE INHIBITORS (ACEi)

The big picture:

Drugs:

Indications:

• Hypertension (first-line, especially with diabetes)
• Heart failure with reduced ejection fraction (HFrEF) - reduces mortality
• Post-MI - reduces remodeling and death
• Diabetic nephropathy - protects kidneys (reduces glomerular pressure)
• Chronic kidney disease (proteinuria reduction)

Side effects:

1. Dry cough (#1 most common - caused by buildup of bradykinin) - affects up to 15% of patients
2. Angioedema (swelling of lips, tongue, throat - can be fatal!) - bradykinin again
3. Hyperkalemia (high potassium - because you're blocking aldosterone effect)
4. Hypotension (especially first dose - "first dose effect")
5. Elevated creatinine (initially expected, but watch for >30% rise = bilateral renal artery stenosis)

Contraindications:

• Pregnancy (all trimesters!) - causes fetal kidney damage and death (BLACK BOX WARNING)
• Bilateral renal artery stenosis - can cause acute kidney failure (ACEi blocks the compensatory efferent vasoconstriction)
• Angioedema history
• Hyperkalemia
• Do NOT combine with ARBs (dual RAAS blockade = more toxicity without more benefit)

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💊 ARBs (Angiotensin Receptor Blockers)

How they work:

Drugs:

Indications: SAME as ACE inhibitors

• Hypertension, heart failure, diabetic nephropathy, post-MI

Key difference from ACEi:

• No cough (because bradykinin still gets broken down - ACEi blocks that)
• Still causes angioedema (less common than ACEi)
• Same hyperkalemia, hypotension risks

Contraindications: Same as ACEi (pregnancy, bilateral RAS, hyperkalemia)

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💊 DIURETICS

Think of diuretics as "kidney plumbing tools" - they make the kidney excrete more water and sodium

WHERE does each diuretic work? (Going from outside to inside kidney tubule):

Proximal Tubule → Loop of Henle → Distal Tubule → Collecting Duct
                      ↑                  ↑               ↑
                  Loop diuretics    Thiazides        K-sparing
                  (furosemide)    (HCTZ)           (spironolactone)

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1. LOOP DIURETICS (most powerful!)

• Acute pulmonary edema (first-line emergency!)
• Heart failure (fluid overload)
• Hypertension with kidney disease
• Hypercalcemia (loop diuretics increase calcium excretion - "loops lose calcium")
• Hypercalcemia emergency: Give furosemide AFTER adequate hydration

• Ototoxicity (hearing loss - especially furosemide IV, and ethacrynic acid is worst; worse with aminoglycosides)
• Thrombocytopenia (rare)
• Onset quick, high ceiling
• Hypokalemia (lose K+) → weakness, arrhythmias
• Alkalosis (metabolic, because H+ and Cl- also lost)
• Also: Hyponatremia, hypomagnesemia, dehydration, hyperuricemia (gout), hyperglycemia

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2. THIAZIDE DIURETICS

• Hypertension (first-line!)
• Heart failure (mild)
• Nephrogenic diabetes insipidus (paradoxically reduces urine output)
• Calcium oxalate kidney stones (thiazides RETAIN calcium → less calcium in urine)
• Osteoporosis (indirectly, calcium retention)
• Hypercalciuria

• Glucose ↑ (hyperglycemia, can worsen diabetes)
• Lipids ↑ (hyperlipidemia)
• Increase uric acid → Gout
• Triggered hypokalemia, hyponatremia, hypomagnesemia
• Calcium INCREASED (opposite of loops!)
• Hypotension, metabolic alkalosis

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3. POTASSIUM-SPARING DIURETICS

• Aldosterone antagonists: Spironolactone, Eplerenone (block aldosterone receptor)
• Direct ENaC blockers: Amiloride, Triamterene (block sodium channels in collecting duct)

• Heart failure (reduces mortality)
• Primary hyperaldosteronism (Conn's syndrome)
• Hypertension (especially resistant)
• Liver cirrhosis with ascites
• Hirsutism/acne in women (anti-androgen effects)
• PCOS

• Hyperkalemia (most important - can cause fatal arrhythmias)
• Gynecomastia (breast tissue in men - blocks androgen receptors)
• Menstrual irregularities
• Eplerenone: More selective, less gynecomastia

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💊 SGLT2 INHIBITORS

What is SGLT2?

Drugs:

Indications:

• Type 2 Diabetes (lowers blood sugar)
• Heart failure (major benefit - reduces hospitalizations and death in HFrEF AND HFpEF)
• Chronic kidney disease (slows progression)
• Proven cardiovascular mortality reduction in high-risk patients

How they lower blood sugar:

Side effects:

1. Genital mycotic infections (UTIs, yeast infections - because glucose in urine feeds bacteria/fungi) - most common complaint
2. UTIs / urinary tract infections
3. Euglycemic DKA (DKA with NORMAL blood sugar - rare but serious! Mechanism: stress → glucagon rises → lipolysis without matching glucose rise → ketones build up)
4. Fournier's gangrene (necrotizing fasciitis of perineum - rare, scary, must stop drug)
5. Volume depletion / hypotension (mild diuretic effect)
6. Canagliflozin specifically: Increased fracture risk, toe/foot amputations (FDA warning - monitor limbs!)
7. Hyperkalemia (mild)

Contraindications:

• Type 1 diabetes (high DKA risk)
• eGFR <20 mL/min (no glycosuric benefit, still cardiovascular benefit for some)
• Recurrent UTIs/genital infections
• Hold before surgery (DKA risk)

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💊 DIGOXIN

What does it do?

Indications:

• Atrial fibrillation / Atrial flutter (rate control - slows the ventricular response)
• Heart failure with reduced EF (improves symptoms, but does NOT reduce mortality)

Narrow therapeutic window:

• Therapeutic: 0.5-2.0 ng/mL (for A-fib), lower (0.5-0.9) preferred for heart failure
• Draw trough levels (at least 6-8 hours after dose)

DIGOXIN TOXICITY - this is a classic exam topic!

• Hypokalemia (most important - K and digoxin compete for same Na/K-ATPase site. Low K = digoxin binds more = more toxic!)
• Hypomagnesemia
• Hypercalcemia (hypercalcemia increases digoxin toxicity)
• Renal failure (digoxin is renally eliminated - accumulates!)
• Drug interactions:
  • Amiodarone, verapamil, quinidine → ALL increase digoxin levels (reduce dose by half!)
  • Clarithromycin, tetracycline, rifampin also interact

• GI: Nausea, vomiting, anorexia, abdominal pain (usually first signs)
• Eyes: Yellow/green visual halos (classic!), blurred vision
• Heart: Bradycardia, heart blocks, PVCs, ventricular tachycardia/fibrillation
• CNS: Confusion, fatigue

1. Stop digoxin
2. Correct electrolytes - give potassium (unless already hyperkalemic), magnesium
3. Digibind (Digoxin Immune Fab) - the antidote! Antibody fragments that bind digoxin and neutralize it
4. Atropine for bradycardia
5. DO NOT give calcium (worsens toxicity - "stone heart")

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💊 CALCIUM CHANNEL BLOCKERS (CCBs)

How they work:

Two major types:

Indications by class:

• All CCBs: Hypertension, angina
• Nifedipine especially: Vasospastic (Prinzmetal) angina, Raynaud's phenomenon
• Verapamil/Diltiazem: Supraventricular arrhythmias, rate control in A-fib

Side effects:

• Peripheral edema (most common - fluid in ankles)
• Flushing, headache
• Reflex tachycardia (especially nifedipine - because vasodilation → reflex fast HR)
• Gingival hyperplasia (swollen gums - nifedipine)

• Bradycardia, AV block, heart failure exacerbation (strongest cardiac effects)
• Constipation (verapamil - classic!)
• Negative inotropy (weakens heart contractions)

Contraindications:

• Verapamil/Diltiazem: Do NOT use with beta blockers (both slow the heart = fatal bradycardia/heart block); Do NOT use in systolic HF (negative inotrope)
• Non-DHPs: Sick sinus syndrome, high-degree AV block, severe LV dysfunction
• Cardiogenic shock

CCB Toxicity (overdose):

• Severe bradycardia, hypotension, cardiogenic shock, AV block
• Treatment: IV calcium gluconate/chloride (overcomes the block), atropine, IV lipid emulsion, vasopressors (norepinephrine), glucagon, high-dose insulin therapy, consider ECMO

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💊 NITRATES

How they work:

• Venodilation → reduces preload (less blood returning to heart) → heart does less work
• Also some arterial dilation → reduces afterload
• Coronary dilation → relieves angina

Drugs:

• Short-acting (sublingual/spray): Nitroglycerin (NTG) - for acute angina attacks
• Long-acting (oral/patch): Isosorbide mononitrate, Isosorbide dinitrate, NTG patch

Indications:

• Acute angina attack (sublingual nitroglycerin - works in minutes)
• Stable angina prevention (long-acting)
• Unstable angina / ACS
• Acute heart failure / pulmonary edema (reduces preload)
• Hypertensive emergency (IV NTG)

Side effects:

1. Headache (#1 most common - throbbing, due to cerebral vasodilation)
2. Hypotension / syncope
3. Reflex tachycardia (especially short-acting NTG)
4. Tolerance (with continuous use - nitrate-free period of 8-12 hours needed each day, usually overnight)
5. Methemoglobinemia (very high doses - hemoglobin can't carry oxygen)

CRITICAL CONTRAINDICATIONS:

1. Phosphodiesterase-5 inhibitors (sildenafil/Viagra, tadalafil/Cialis) - FATAL hypotension - absolute contraindication! Both drugs increase cGMP, combined effect drops BP severely
2. Right ventricular infarction (these patients need preload - giving nitrates removes preload → crash)
3. Hypertrophic obstructive cardiomyopathy (reducing preload worsens outflow obstruction)
4. Severe hypotension, shock

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💊 BETA BLOCKERS (β-Blockers)

How they work:

• β1 blockade → ↓ heart rate, ↓ contractility, ↓ AV conduction → lower BP and cardiac work
• β2 blockade → bronchoconstriction, vasoconstriction, blocks glycogenolysis

Types:

• Cardioselective (β1 selective - "AMEBA"): Atenolol, Metoprolol, Esmolol, Bisoprolol, Acebutolol - fewer respiratory effects at low doses
• Non-selective: Propranolol, Nadolol, Timolol, Pindolol
• Mixed α + β blockers: Carvedilol, Labetalol (block both α and β receptors → more vasodilation)
• Pindolol, Acebutolol: Have intrinsic sympathomimetic activity (ISA) - partial agonists

Indications:

• Hypertension
• Heart failure (carvedilol, metoprolol succinate, bisoprolol - these reduce mortality!)
• Post-MI - reduces mortality, prevents re-infarction
• Angina (reduces oxygen demand by slowing heart)
• Atrial fibrillation / flutter (rate control)
• SVT (esmolol for acute, propranolol for prevention)
• Hypertrophic cardiomyopathy (slowing HR improves filling)
• Pheochromocytoma (give ALPHA blocker FIRST, then beta blocker - NEVER beta first alone!)
• Thyroid storm (propranolol reduces HR and blocks T4→T3 conversion)
• Migraine prophylaxis (propranolol)
• Essential tremor (propranolol)
• Glaucoma (timolol eye drops)
• Portal hypertension/varices prophylaxis (propranolol, nadolol)

Side effects:

1. Bradycardia / AV block
2. Hypotension
3. Bronchoconstriction (especially non-selective - problem in asthma/COPD patients)
4. Fatigue, depression
5. Impaired glucose metabolism - masks hypoglycemia symptoms (sweating still present, but tachycardia masked!) - caution in insulin-dependent diabetics
6. Cold extremities (vasoconstriction)
7. Sexual dysfunction
8. Hypertriglyceridemia (mild)
9. Rebound hypertension/angina if stopped abruptly - always taper off

Contraindications:

• Asthma / COPD (bronchoconstriction) - use cardioselective if must use
• Decompensated heart failure (OK once stable)
• High-degree AV block, sick sinus syndrome (without pacemaker)
• Bradycardia
• Do NOT combine with verapamil/diltiazem (additive bradycardia/heart block)
• Pheochromocytoma without alpha blockade first

Beta Blocker Toxicity:

• Severe bradycardia, hypotension, AV block, heart failure, bronchospasm
• Treatment: Glucagon (first-line! stimulates cAMP independently of β receptors), IV fluids, atropine, cardiac pacing, high-dose insulin, IV lipid emulsion, consider ECMO

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💊 ANTIARRHYTHMICS

Vaughan-Williams Classification (4 classes):

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CLASS IA (Na+ blockers + slow conduction + prolong QT)

• Quinidine: Torsades de Pointes (dangerous QT prolongation), cinchonism (tinnitus, headache, dizziness), thrombocytopenia, diarrhea
• Procainamide: Drug-induced lupus (positive ANA, anti-histone antibodies) - reversible on stopping
• Disopyramide: Strong anticholinergic effects, negative inotrope

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CLASS IB (Na+ blockers + shorten action potential)

• IV only (first-pass effect if oral)
• CNS toxicity: Tremors, tinnitus, seizures, dizziness
• Good for ventricular tachycardia

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CLASS IC (Strongest Na+ blockers, minimal effect on repolarization)

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CLASS III (K+ channel blockers - prolong QT interval)

1. Pulmonary toxicity (most serious - interstitial pneumonitis, pulmonary fibrosis; check CXR, DLCO regularly)
2. Thyroid toxicity: Can cause BOTH hyperthyroidism AND hypothyroidism (rich in iodine - 37% iodine by weight!)
3. Hepatotoxicity (monitor liver function tests)
4. Corneal microdeposits (almost everyone gets this, usually not clinically significant but causes visual halos)
5. Photosensitivity + blue-gray skin discoloration (prolonged use)
6. Peripheral neuropathy, ataxia
7. QT prolongation - paradoxically, less Torsades than other class III drugs

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CLASS IV (covered under calcium channel blockers above)

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ADENOSINE - special antiarrhythmic:

• Slows AV node conduction (activates K+ channels in AV node)
• #1 drug for ACUTE SVT termination
• Very short half-life (seconds!) - given as rapid IV push
• Side effects: Transient chest pain, flushing, dyspnea, brief asystole (terrifying but brief)
• Contraindicated in WPW with pre-excited A-fib, 2nd/3rd degree AV block

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QUICK REFERENCE: TOXICITY ANTIDOTES TABLE

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FINAL EXAM SUMMARY: KEY MNEMONICS

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How to use this guide for your exam:

1. Start with the Autonomic System section first - it's the foundation. Once you understand adrenergic vs cholinergic receptors, everything else makes more sense.
2. Then Antipsychotics - memorize the 4 dopamine pathways and the EPS/NMS distinction.
3. Then Antidepressants - focus on SSRIs first (safest, most tested), then TCAs (most dangerous in overdose), then MAOIs (most interactions).
4. For cardiovascular drugs, memorize the RAAS pathway once and ACEi/ARBs will click instantly.
5. For diuretics, just remember WHERE each one works in the kidney tubule.

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The 5 Most Tested "Gotcha" Topics:

1. Serotonin Syndrome vs NMS - clonus/hyperreflexia (serotonin) vs lead-pipe rigidity (NMS)
2. Digoxin toxicity - always triggered by hypokalemia; antidote = Digibind
3. TCA overdose - wide QRS; treat with sodium bicarbonate (not physostigmine!)
4. Nitrate + sildenafil = fatal hypotension - absolute contraindication
5. ACEi in pregnancy = absolute contraindication all trimesters