1. Statins 2. Nitroglicerin 3. Ccbs verapamil vs diltiazem vs nifedipine 4. Metformin 5. Sulfanylurea drugs 6. Propylthiouracil 7. Levothyroxine 8. Tetracycline 9. Glucocorticoids 10. Diuretics 11. Anticoagulants 12.dpp inhibitors 13. Sglt2 inhibitors 14. Digoxin 15. Ace inhibitors 16. Muscarinic antagonists 17. Aspirin/clopidogrel 18. Beta 2 agonists 19. Insulin all types 20. Fibrates quick revision pharma notes on this drugs

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I have comprehensive data from the textbooks. Now let me compile the complete pharmacology notes for all 20 drug classes. I have enough from the textbooks - let me write the full answer:

Quick Revision Pharmacology Notes: 20 Drug Classes

1. STATINS (HMG-CoA Reductase Inhibitors)

Drugs: Atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin

Mechanism: Competitively inhibit HMG-CoA reductase (rate-limiting step in hepatic cholesterol synthesis) → ↓ intracellular cholesterol → ↑ LDL receptor expression → ↑ LDL clearance from plasma

Effects:

↓ LDL-C by 30-55% (high-intensity = atorva 40-80mg / rosuva 20-40mg)
Doubling the dose gives only ~6% additional LDL reduction ("rule of 6")
Modest ↓ TGs; modest ↑ HDL
Pleiotropic effects: anti-inflammatory, plaque stabilization

Indications: ASCVD (secondary prevention), high CV risk (primary prevention), familial hypercholesterolemia

Side effects:

Myalgia/myopathy (3-5%) - check CK if symptomatic; rhabdomyolysis rare
↑ Transaminases (ALT/AST) - usually mild and transient
Slight ↑ risk of new-onset T2DM (benefits far outweigh this risk)
Increased myopathy risk with: fibrates (especially gemfibrozil), erythromycin/azoles, cyclosporine, older age, renal insufficiency

Key point: Taken once daily; most are metabolized by CYP3A4 (except pravastatin - not CYP dependent)

(Harrison's Internal Medicine 22E, p.3294 - Lippincott Biochemistry 8e)

2. NITROGLYCERIN (Organic Nitrates)

Drugs: Nitroglycerin (GTN), isosorbide dinitrate, isosorbide mononitrate

Mechanism: Prodrug → releases NO (nitric oxide) → activates guanylate cyclase → ↑ cGMP → smooth muscle relaxation → venodilation (primarily) and arterial dilation

Hemodynamic effects:

Venodilation → ↓ preload → ↓ myocardial O₂ demand (main effect)
Coronary vasodilation → relieves vasospasm, dilates collaterals
At high doses: arterial dilation → ↓ afterload

Routes & Uses:

Sublingual: onset 1-3 min, duration 30 min → acute angina
IV: hypertensive emergencies (5 µg/min, titrate up)
Transdermal patch / oral long-acting: angina prophylaxis (must have nitrate-free interval 10-12 h to avoid tolerance)

Side effects: Headache (vasodilation), hypotension, reflex tachycardia, methemoglobinemia (rare at high doses)

Contraindications: Concurrent PDE-5 inhibitors (sildenafil) → severe hypotension; obstructive cardiomyopathy, severe aortic stenosis

Tolerance: Develops with continuous use due to depletion of sulfhydryl groups; prevent with nitrate-free interval

(Comprehensive Clinical Nephrology 7e; Goldman-Cecil Medicine)

3. CALCIUM CHANNEL BLOCKERS (CCBs) - Verapamil vs Diltiazem vs Nifedipine

Feature	Verapamil (phenylalkylamine)	Diltiazem (benzothiazepine)	Nifedipine (dihydropyridine)
Selectivity	Cardiac > vascular	Cardiac + vascular (intermediate)	Vascular >> cardiac
HR effect	↓↓ (most negative chronotropy)	↓ (moderate)	↑ reflex tachycardia
Contractility	↓↓ (negative inotropy)	↓ (moderate)	Minimal
Conduction	↓↓ AV node	↓ AV node	Minimal
Vasodilation	Moderate	Moderate	Marked
Main uses	SVT, angina, HTN, rate control in AFib	SVT, angina, HTN, rate control	HTN, angina, Raynaud's, tocolysis
Avoid in	HF, WPW+AFib, beta-blocker combo	HF, WPW	Unstable angina (short-acting)

Mechanism: Block L-type voltage-gated Ca²⁺ channels → ↓ Ca²⁺ entry into cardiac and vascular smooth muscle cells

Key side effects:

Verapamil: Constipation (hallmark), bradycardia, AV block, ↑ digoxin levels by 50-90%
Diltiazem: Bradycardia, AV block (less than verapamil), ↑ digoxin levels
Nifedipine: Peripheral edema, flushing, headache, reflex tachycardia (short-acting form)

(Goldman-Cecil Medicine; Kaplan & Sadock's)

4. METFORMIN (Biguanide)

Mechanism:

Primarily: ↓ hepatic gluconeogenesis (via AMPK activation)
↓ intestinal glucose absorption
↑ peripheral insulin sensitivity (muscle glucose uptake)
Does NOT stimulate insulin secretion → no hypoglycemia as monotherapy

Pharmacokinetics: Well-absorbed orally; not protein-bound; not metabolized; excreted unchanged in urine (renal clearance)

Indications: First-line T2DM (initiated at diagnosis), prediabetes, PCOS

Adverse effects:

GI (diarrhea, nausea, vomiting) - minimize by titrating slowly and taking with meals
Lactic acidosis (rare but potentially fatal) - risk ↑ with renal failure, liver disease, sepsis
Vitamin B₁₂ deficiency with long-term use
Weight neutral/modest weight loss

Contraindications: eGFR <30 mL/min/1.73m², acute MI, sepsis, exacerbation of heart failure, IV contrast (hold temporarily), alcohol abuse, age >80y (use caution)

(Lippincott Pharmacology, p.812)

5. SULFONYLUREAS

Drugs (2nd generation): Glyburide (glibenclamide), glipizide, glimepiride

Mechanism: Block ATP-sensitive K⁺ channels on pancreatic β-cells → membrane depolarization → voltage-gated Ca²⁺ channels open → Ca²⁺ influx → insulin exocytosis

Pharmacokinetics: Oral; protein-bound; hepatic metabolism; renal/fecal excretion; duration 12-24h

Adverse effects:

Hypoglycemia (main risk - especially glyburide in renal impairment/elderly)
Weight gain
Hyperinsulinemia

Key distinctions:

Glyburide: avoid in renal impairment (active metabolites accumulate)
Glipizide/glimepiride: safer in elderly and renal impairment
Enhanced by: NSAIDs, sulfonamides, fluconazole, β-blockers (mask hypoglycemia symptoms)
Reduced by: thiazides, glucocorticoids, rifampin

(Lippincott Pharmacology, p.813-814; Guyton & Hall Physiology)

6. PROPYLTHIOURACIL (PTU)

Class: Thioamide antithyroid drug (with methimazole)

Mechanism (2 main actions):

Inhibits thyroid peroxidase → blocks iodine organification and coupling reactions (blocks T3/T4 synthesis)
Inhibits peripheral conversion of T4 → T3 (via inhibition of deiodinase) - this is unique to PTU vs methimazole

Pharmacokinetics: Oral; short duration 6-8h (methimazole lasts 24h); delayed onset (doesn't destroy already-formed hormone)

Indications: Hyperthyroidism (Graves' disease), thyroid storm, 1st trimester pregnancy (methimazole is teratogenic in 1st trimester; PTU preferred then switch at 2nd trimester)

Adverse effects:

Nausea, GI distress, rash
Agranulocytosis (0.1-0.5%) - educate patient to report fever/sore throat
Hepatotoxicity (PTU black box warning) - rare fulminant hepatic necrosis
Hypothyroidism (if overdosed)

Key comparison - PTU vs methimazole:

Methimazole: once daily dosing, preferred except 1st trimester pregnancy
PTU: 3x daily dosing, more hepatotoxic, but inhibits T4→T3 conversion (preferred in thyroid storm)

(Katzung Pharmacology 16e, p.1094)

7. LEVOTHYROXINE (T₄ replacement)

Mechanism: Synthetic T₄ → converted peripherally to active T₃ → binds nuclear receptors → gene expression → protein synthesis (↑ BMR, CNS maturation, growth, cardiac contractility)

Pharmacokinetics:

Oral; T½ ~7 days (allowing once-daily dosing)
Average replacement dose: 1.7 µg/kg/day (lean body weight)
Absorbed in jejunum/ileum; best absorbed on empty stomach (30-60 min before food)
Maximum effect seen after 6-8 weeks

Indications: Hypothyroidism (primary, secondary), myxedema coma (IV), TSH suppression in thyroid cancer

Monitoring: TSH (goal = normal range in primary hypothyroidism); free T4

Drug interactions that decrease absorption: Calcium, iron, antacids, cholestyramine (separate by 4h) Drug interactions that increase clearance: Rifampin, phenytoin, carbamazepine (enzyme inducers)

Adverse effects (excess): Palpitations, AF, angina, osteoporosis, anxiety, heat intolerance, diarrhea Note: ATA recommends against routine combination with liothyronine (T3)

(Katzung 16e; Goodman & Gilman's)

8. TETRACYCLINES

Drugs: Tetracycline, doxycycline, minocycline, tigecycline (glycylcycline)

Mechanism: Reversibly bind 30S ribosomal subunit → block tRNA attachment to mRNA-ribosome complex → inhibit bacterial protein synthesis (bacteriostatic)

Spectrum: Broad - Gram+, Gram-, atypicals (Mycoplasma, Chlamydia, Rickettsia), spirochetes (Borrelia), Vibrio cholerae, some protozoa

Key clinical uses:

Doxycycline: Chlamydia, Lyme disease, Rocky Mountain spotted fever (Rickettsia), atypical pneumonia, MRSA (community), malaria prophylaxis, acne
Minocycline: Acne, MRSA
Tetracycline: H. pylori (part of regimen), acne

Adverse effects:

GI: nausea, diarrhea, esophageal ulceration (take with plenty of water, stay upright)
Photosensitivity (especially doxycycline)
Teeth discoloration and impaired bone growth in children <8y and fetus - contraindicated
Hepatotoxicity (IV, high dose)
Fanconi syndrome (expired tetracycline)

Contraindications: Pregnancy, children <8y, severe renal impairment (except doxycycline - hepatically eliminated)

Resistance: Active efflux pumps (plasmid-mediated) or ribosomal protection proteins

Interactions: Chelate with Ca²⁺, Mg²⁺, Al³⁺, Fe²⁺ (antacids, dairy, iron) → ↓ absorption; doxycycline preferred in renal failure

(Lippincott Pharmacology; Harrison's 22E)

9. GLUCOCORTICOIDS

Drugs: Hydrocortisone, prednisolone, methylprednisolone, dexamethasone, budesonide (inhaled)

Mechanism: Bind cytosolic glucocorticoid receptor → translocate to nucleus → bind glucocorticoid response elements → regulate gene transcription:

↓ pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-α)
↓ arachidonic acid release (via lipocortin/annexin → ↓ PLA₂)
↓ COX-2 expression
↑ anti-inflammatory proteins; ↓ lymphocyte/eosinophil/monocyte count
↑ neutrophil count (demargination)

Metabolic effects: Hyperglycemia, hyperlipidemia, central obesity, protein catabolism, negative Ca²⁺ balance

Indications: Asthma/COPD, IBD, autoimmune diseases (SLE, RA), organ transplant, adrenal insufficiency (replacement), cerebral edema (dexamethasone), septic shock (hydrocortisone), allergic reactions

Side effects of long-term use:

Cushing syndrome (truncal obesity, moon face, buffalo hump, striae)
Osteoporosis → add calcium, vitamin D, bisphosphonate
Immunosuppression → opportunistic infections
Peptic ulcer (especially with NSAIDs)
HPA axis suppression (taper gradually; never stop abruptly)
Hyperglycemia, hypertension, hypokalemia, fluid retention
Cataracts (posterior subcapsular), glaucoma
Avascular necrosis of femoral head
Growth retardation in children
Psychiatric effects (euphoria, psychosis)

Relative potencies: Hydrocortisone 1 | Prednisolone 4 | Methylprednisolone 5 | Dexamethasone 25-30

10. DIURETICS

Loop Diuretics (e.g., Furosemide, bumetanide, torasemide)

MOA: Inhibit Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2) in thick ascending limb of loop of Henle → lose Na⁺, K⁺, Cl⁻, Ca²⁺, Mg²⁺, H₂O Use: Pulmonary edema, HF, HTN, hypercalcemia, hyperkalemia SE: Hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, metabolic alkalosis, ototoxicity (high dose/IV), hyperuricemia, dehydration

Thiazides (e.g., Hydrochlorothiazide, chlorthalidone, indapamide)

MOA: Inhibit Na⁺/Cl⁻ cotransporter (NCC) in distal convoluted tubule Use: HTN (first-line), edema, nephrolithiasis (Ca²⁺ stones - ↓ urinary Ca²⁺), nephrogenic DI SE: Hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercalcemia (unlike loop diuretics), metabolic alkalosis Contraindication: Gout (relative), sulfa allergy

Potassium-Sparing Diuretics

Spironolactone/eplerenone (aldosterone antagonists): Block mineralocorticoid receptor → used in HF (↓ mortality), primary hyperaldosteronism, cirrhotic ascites; SE: hyperkalemia, gynecomastia (spironolactone)
Amiloride/triamterene (ENaC blockers): Block Na⁺ channels in collecting duct; used to prevent K⁺ loss with other diuretics; SE: hyperkalemia

Carbonic Anhydrase Inhibitors (Acetazolamide)

MOA: Block CA → ↓ HCO₃⁻ reabsorption in proximal tubule Use: Glaucoma, altitude sickness, alkalinize urine (salicylate/methotrexate OD) SE: Metabolic acidosis, hypokalemia, sulfa allergy cross-reaction

Osmotic Diuretics (Mannitol)

MOA: Non-absorbable solute → osmotic gradient → draws water into tubular lumen Use: ↑ ICP, acute angle-closure glaucoma, oliguric renal failure Caution: Pulmonary edema (initial fluid shift from intracellular to extracellular)

11. ANTICOAGULANTS

Heparins

	UFH (Unfractionated)	LMWH (e.g., Enoxaparin)
MOA	↑ antithrombin III activity → inactivates IIa (thrombin) + Xa	↑ antithrombin III → mainly inactivates Xa
Route	IV/SubQ	SubQ
Monitor	aPTT	Not routinely (anti-Xa if needed)
Reversal	Protamine sulfate (100%)	Protamine (60%)
HIT risk	Higher	Lower

Warfarin

MOA: Inhibits vitamin K epoxide reductase → ↓ synthesis of factors II, VII, IX, X, protein C & S (vitamin K-dependent, carboxylation required) Monitor: INR (target 2-3 for most indications; 2.5-3.5 for mechanical valves) Reversal: Vitamin K (slow), FFP (fast), 4-factor PCC (fastest) Interactions: Numerous - enzyme inducers ↓ effect (rifampin), inhibitors ↑ effect (azoles, amiodarone) Onset: 3-5 days (factor VII depleted first - shortest half-life)

Direct Oral Anticoagulants (DOACs)

Direct thrombin inhibitors: Dabigatran (oral); argatroban, bivalirudin (IV)
Factor Xa inhibitors: Rivaroxaban, apixaban, edoxaban
Reversal: Idarucizumab (dabigatran); andexanet alfa (Xa inhibitors)
Advantages: Predictable PK, no routine monitoring, fewer drug interactions vs warfarin

12. DPP-4 INHIBITORS (Gliptins)

Drugs: Sitagliptin, saxagliptin, linagliptin, alogliptin

Mechanism: Inhibit DPP-4 (dipeptidyl peptidase-4) enzyme → prevent degradation of incretins (GLP-1 and GIP) → ↑ active GLP-1 → glucose-dependent ↑ insulin secretion + ↓ glucagon secretion

Key feature: Glucose-dependent mechanism → low hypoglycemia risk as monotherapy

Effects: ↓ postprandial and fasting glucose; weight neutral

Indications: T2DM (add-on or monotherapy)

Adverse effects:

Upper respiratory tract infections (nasopharyngitis)
Urinary tract infections
Rare: pancreatitis (monitor amylase/lipase)
Saxagliptin/alogliptin: possible ↑ risk of HF hospitalization (use caution)
Rare: bullous pemphigoid (skin rash)

Renal adjustment: Most require dose adjustment in renal impairment; linagliptin is the exception (hepatically eliminated - no dose adjustment needed)

(Lippincott Pharmacology, p.818-819)

13. SGLT2 INHIBITORS (Gliflozins)

Drugs: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin

Mechanism: Inhibit sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubule → block glucose reabsorption → glucosuria (~70-80 g/day) → ↓ blood glucose; also ↓ Na⁺ reabsorption → natriuresis

Effects:

↓ HbA1c by ~0.5-1%
Weight loss (~2-3 kg) due to caloric loss
↓ Blood pressure (natriuretic effect)
Cardioprotective: ↓ HF hospitalization, ↓ CV mortality (empagliflozin EMPA-REG, canagliflozin CANVAS, dapagliflozin DAPA-HF)
Renoprotective: ↓ progression of diabetic nephropathy

Indications: T2DM, HF with reduced ejection fraction (HFrEF), CKD (dapagliflozin, canagliflozin)

Adverse effects:

Genital mycotic infections (vulvovaginal candidiasis/balanitis) - most common
UTIs
Diabetic ketoacidosis (euglycemic DKA) - even with normal glucose; hold before surgery
Hypotension (especially in elderly, on diuretics)
Bone fractures (canagliflozin)
Fournier's gangrene (necrotizing fasciitis of perineum - rare but serious)
↑ LDL (small)

(Lippincott Pharmacology, p.1267)

14. DIGOXIN

Class: Cardiac glycoside

Mechanism (dual):

Inhibits Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → ↓ Na⁺/Ca²⁺ exchanger activity → ↑ intracellular Ca²⁺ → positive inotropy
Vagomimetic (↑ vagal tone) → ↓ HR (negative chronotropy), ↓ AV node conduction (↑ PR interval, rate control)

Indications:

Rate control in atrial fibrillation (especially in HFrEF)
HFrEF (reduces symptoms and hospitalizations; does NOT improve mortality)

Pharmacokinetics: Narrow therapeutic index (target serum level 0.5-0.9 ng/mL for HF); renal excretion; long half-life (~36-48h)

Toxicity signs:

GI: nausea, vomiting, anorexia (early)
Visual: yellow-green halos (xanthopsia)
Cardiac: bradycardia, heart block, any arrhythmia (especially PAT with block, bigeminy)
CNS: confusion

Factors that increase toxicity:

Hypokalemia (K⁺ competes with digoxin for Na/K-ATPase)
Hypomagnesemia, hypercalcemia
Renal failure (↓ clearance)
Drug interactions: Verapamil ↑ digoxin level 50-90%; amiodarone ↑; quinidine ↑; diltiazem ↑

Toxicity treatment: Digoxin immune Fab (Digibind), correct electrolytes, avoid electrical cardioversion

15. ACE INHIBITORS

Drugs: Enalapril, lisinopril, ramipril, captopril, perindopril (suffix "-pril")

Mechanism: Inhibit ACE → block conversion of angiotensin I → angiotensin II; also block bradykinin degradation (bradykinin accumulates)

Effects:

↓ Ang II → vasodilation (↓ preload and afterload), ↓ aldosterone (↓ Na/H₂O retention, ↓ K⁺ loss), ↓ sympathetic activation
Bradykinin accumulation → cough (ACE inhibitor cough)
↓ Glomerular efferent arteriole tone → ↓ GFR initially, but long-term renoprotection

Indications: HTN, HFrEF (↓ mortality), post-MI, diabetic nephropathy (1st choice), CKD with proteinuria, prevention of ASCVD events

Side effects:

Dry cough (10-15%) - bradykinin mediated; switch to ARB (sartans) if intolerable
Angioedema (rare but life-threatening - bradykinin) - switch to ARB (NOT the same risk)
Hyperkalemia (↓ aldosterone)
First-dose hypotension (especially in volume-depleted/diuretic users)
Acute kidney injury in bilateral renal artery stenosis (remove efferent arteriole support)
Teratogenic (2nd/3rd trimester) - cause renal agenesis, oligohydramnios

16. MUSCARINIC ANTAGONISTS (Anticholinergics)

Drugs: Atropine, scopolamine, ipratropium, tiotropium, oxybutynin, tolterodine, benztropine, glycopyrrolate, hyoscine

Mechanism: Competitively block muscarinic receptors (M1-M5) → block parasympathetic effects

Effects by organ:

Heart: ↑ HR (M2 block), ↑ AV conduction
Eye: Mydriasis (M3 block), cycloplegia (loss of accommodation), ↑ IOP
Lungs: Bronchodilation, ↓ secretions (ipratropium/tiotropium - inhaled for COPD/asthma)
GI: ↓ motility, ↓ secretions, constipation, dry mouth
Bladder: Urinary retention (M3 block), relaxes detrusor → used for overactive bladder
CNS: Scopolamine → motion sickness, sedation; atropine/benztropine → Parkinson's

Mnemonic - Toxicity ("Hot as hare, dry as bone, red as beet, blind as bat, mad as hatter, full as flask"):

Hyperthermia, dry skin/mouth, flushing, mydriasis, delirium, urinary retention

Specific uses:

Atropine: bradycardia, organophosphate poisoning, pre-anesthetic
Ipratropium: COPD, acute asthma (add-on)
Tiotropium: COPD maintenance (once daily - long-acting)
Oxybutynin/tolterodine: overactive bladder
Scopolamine: motion sickness, PONV
Benztropine: Parkinson's disease, antipsychotic-induced extrapyramidal effects

Contraindications: Narrow-angle glaucoma, BPH, pyloric stenosis

17. ASPIRIN / CLOPIDOGREL (Antiplatelet drugs)

Aspirin

MOA: Irreversibly acetylates COX-1 (and COX-2) → ↓ TXA₂ synthesis in platelets → ↓ platelet aggregation; effect lasts platelet lifetime (~7-10 days) Low dose (75-100 mg): Antiplatelet (selectively inhibits platelet COX-1, as platelets lack nucleus for new COX) Indications: ACS, post-MI, stroke/TIA prevention, AF, post-PCI SE: GI bleeding, peptic ulcer, bleeding; aspirin-induced asthma (COX-1 → prostaglandin shunting to leukotrienes); Reye's syndrome in children with viral illness; tinnitus (salicylism at high doses)

Clopidogrel (and prasugrel, ticagrelor, ticlopidine)

MOA: P2Y12 ADP receptor antagonist → blocks ADP-mediated platelet activation → ↓ aggregation

Clopidogrel/prasugrel: irreversible binding (prodrug - requires CYP2C19 activation for clopidogrel)
Ticagrelor: reversible binding, no activation needed (faster, more potent)

Indications: ACS, post-PCI (DAPT with aspirin), peripheral arterial disease; ticagrelor preferred over clopidogrel in high-risk ACS

Key: CYP2C19 poor metabolizers → reduced clopidogrel efficacy (genetic testing in some patients); PPIs (especially omeprazole) reduce clopidogrel effect

SE: Bleeding, TTP (ticlopidine > clopidogrel), dyspnea (ticagrelor - adenosine-mediated)

18. BETA-2 AGONISTS

Drugs:

Short-acting (SABAs): Salbutamol (albuterol), terbutaline, fenoterol - onset 5 min, duration 4-6h
Long-acting (LABAs): Salmeterol, formoterol - onset: formoterol rapid, salmeterol 30 min; duration 12h
Ultra-long-acting: Indacaterol (once daily)

Mechanism: Stimulate β₂-adrenergic receptors → ↑ cAMP → PKA activation → smooth muscle relaxation → bronchodilation; also ↑ mucociliary clearance, ↓ mast cell degranulation

Clinical uses:

SABAs: Rescue therapy in asthma and COPD exacerbation; terbutaline IV/SubQ for tocolysis (preterm labor), anaphylaxis (salbutamol nebulized)
LABAs: Maintenance therapy in asthma (always with ICS - never alone in asthma) and COPD; salmeterol for nocturnal asthma

Side effects:

Tachycardia, palpitations (β₁ spillover)
Tremor (skeletal muscle)
Hypokalemia (↑ K⁺ uptake into cells - Na/K-ATPase activation)
Hyperglycemia
Headache
Paradoxical bronchospasm (with overuse)

LABA warning: Never use LABAs alone in asthma (↑ asthma-related death risk without ICS)

19. INSULIN - ALL TYPES

Type	Example	Onset	Peak	Duration	Key Use
Rapid-acting	Lispro, Aspart, Glulisine	10-15 min	1-1.5 h	3-5 h	Mealtime bolus
Regular (short)	Regular (Humulin R)	30-60 min	2-4 h	6-10 h	Meals (30 min before), DKA (IV)
Intermediate	NPH (Humulin N)	1-2 h	4-10 h	12-18 h	Twice daily basal
Long-acting	Glargine (U-100/300), Detemir	2-4 h	No peak (glargine) / small peak (detemir)	20-24 h (glargine), 6-24 h (detemir)	Once/twice daily basal
Ultra long-acting	Degludec	1 h	No peak	>42 h	Once daily basal

Mechanism: Binds insulin receptor (tyrosine kinase) → GLUT4 translocation → ↑ glucose uptake (muscle, fat); ↑ glycogen synthesis; ↑ protein synthesis; ↓ gluconeogenesis; ↓ lipolysis

Key points:

Only regular insulin can be given IV (for DKA, hyperkalemia, critical illness)
Glargine/detemir: cannot be mixed with other insulins
Rapid-acting analogs: taken immediately before or with meals
NPH: only intermediate that can be mixed
Lipodystrophy with repeated injection at same site (rotate sites)

Adverse effects: Hypoglycemia (main risk - treat with glucose), weight gain, hypokalemia (↑ K⁺ into cells), lipodystrophy, injection site reactions

Basal-bolus regimen: Long-acting (glargine) + rapid-acting (lispro/aspart) at meals - best mimics physiologic insulin secretion

20. FIBRATES

Drugs: Gemfibrozil, fenofibrate, bezafibrate, ciprofibrate

Mechanism: Activate PPARα (peroxisome proliferator-activated receptor alpha, nuclear receptor) → ↑ lipoprotein lipase (LPL) expression → ↑ VLDL clearance → ↓ TG; also ↑ HDL synthesis (↑ apoA-I and apoA-II); modest ↓ LDL

Effects on lipids:

↓ TGs by 30-50% (most potent TG-lowering drug class)
↑ HDL by 10-20%
Modest ↓ LDL (may paradoxically ↑ LDL in hypertriglyceridemia)

Indications:

Hypertriglyceridemia (TG >500 mg/dL → pancreatitis prevention)
Mixed dyslipidemia (combined with statin)
Severe hypertriglyceridemia

Adverse effects:

GI: nausea, dyspepsia, abdominal pain
Myopathy - risk markedly ↑ when combined with statins, especially gemfibrozil (inhibits statin glucuronidation → ↑ statin levels); fenofibrate is safer combination with statins
Cholelithiasis (gallstones) - ↑ cholesterol secretion into bile
Hepatotoxicity (↑ LFTs)
Gemfibrozil: inhibits CYP2C8 → ↑ repaglinide levels (avoid combination)

Key combination note: Gemfibrozil + statin = high myopathy/rhabdomyolysis risk; fenofibrate + statin is preferred when combination needed

Quick Reference Summary Table

Drug Class	MOA (1 line)	Biggest SE to Know
Statins	↓ HMG-CoA reductase → ↓ LDL	Myopathy/rhabdomyolysis
Nitroglycerin	NO → ↑ cGMP → vasodilation	Headache, hypotension; tolerance
Verapamil	L-Ca²⁺ block (cardiac)	Constipation, AV block, ↑ digoxin
Diltiazem	L-Ca²⁺ block (cardiac+vasc)	Bradycardia, AV block
Nifedipine	L-Ca²⁺ block (vascular)	Edema, reflex tachycardia
Metformin	↓ Hepatic gluconeogenesis	Lactic acidosis (renal failure)
Sulfonylureas	Block K-ATP channel → ↑ insulin	Hypoglycemia, weight gain
PTU	Inhibit TPO + deiodinase	Agranulocytosis, hepatotoxicity
Levothyroxine	T4 replacement → nuclear receptor	Over-replacement: AF, osteoporosis
Tetracycline	30S block → ↓ protein synthesis	Teeth/bone (children), photosensitivity
Glucocorticoids	↓ cytokines, ↓ PLA₂	HPA suppression, Cushing, osteoporosis
Loop diuretics	NKCC2 inhibition	Hypokalemia, ototoxicity
Thiazides	NCC inhibition (DCT)	Hypokalemia, hyperuricemia, hyperCa
Spironolactone	Aldosterone antagonist	Hyperkalemia, gynecomastia
Warfarin	↓ Vit K factors II,VII,IX,X	Bleeding; teratogenic
Heparin (UFH)	↑ ATIII → ↓ IIa + Xa	HIT, bleeding
DOACs	Direct IIa or Xa inhibition	Bleeding
DPP-4 inhibitors	↑ active GLP-1 → glucose-dep insulin	URTI, rare pancreatitis
SGLT2 inhibitors	Block PCT glucose reabsorption	Genital mycosis, euDKA
Digoxin	Inhibit Na/K-ATPase → ↑ Ca²⁺	Toxicity: yellow vision, arrhythmia
ACE inhibitors	↓ Ang II, ↑ bradykinin	Cough, angioedema, hyperK, teratogen
Muscarinic antagonists	Block M receptors	Dry mouth, retention, mydriasis
Aspirin	Irreversible COX-1 block → ↓ TXA₂	GI bleed, Reye's
Clopidogrel	P2Y12 ADP receptor block	Bleeding, TTP (ticlopidine)
Beta-2 agonists	↑ cAMP → bronchodilation	Tachycardia, hypokalemia, tremor
Insulin (rapid)	GLUT4 ↑, glucose uptake	Hypoglycemia, weight gain
Fibrates	PPARα agonist → ↑ LPL, ↑ HDL	Myopathy (with statins), gallstones

Sources: Harrison's Internal Medicine 22E (2025); Lippincott Illustrated Reviews Pharmacology; Katzung's Basic and Clinical Pharmacology 16e; Goodman & Gilman's Pharmacological Basis of Therapeutics; Guyton & Hall Medical Physiology; Goldman-Cecil Medicine

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