Preparatory Mindset
Cardiovascular drugs target hypertension, angina, and heart failure. For hypertension: first-line agents are ACE inhibitors/ARBs, CCBs, thiazide diuretics, and β-blockers. Know the mechanism, indications, and contraindications for each class. For angina: nitrates (vasodilate), β-blockers (↓ HR/contractility), CCBs (vasodilate).
Core Concepts
Ch09: Cardiovascular
Part A: Cardiac Glycosides (Digoxin)
| Aspect | Detail |
|--------|--------|
| MOA | Inhibit Na+/K+-ATPase → ↑ intracellular Na+ → ↓ Na+/Ca2+ exchange → ↑ intracellular Ca2+ → ↑ contractility (positive inotropy) |
| Best Use | HF with atrial fibrillation (slows AV conduction + ↑ contractility) |
| Toxicity Triad | GI (nausea/vomiting) + CNS (dizziness, blurred/colored vision) + Arrhythmias |
| Risk Factors | Hypokalemia, hypomagnesemia, hypercalcemia, renal impairment, elderly |
| Drug Interactions | Quinidine (↑ digoxin levels); diuretics (↓ K+ → ↑ toxicity); amiodarone (↑ levels) |
| Treatment of Toxicity | Atropine (bradycardia); Phenytoin/Lidocaine (arrhythmias); Digoxin-specific Fab fragments |
Part B: Antihypertensive Agents
Classification (MUST KNOW)
| Class | Example | MOA | Key Side Effects |
|-------|---------|-----|-----------------|
| ACE Inhibitors | Captopril, Enalapril | ↓ Ang II formation; ↑ bradykinin | Cough (bradykinin-mediated), hyperkalemia, angioedema |
| ARBs | Losartan, Irbesartan, Valsartan | Block AT1 receptor | No cough (unlike ACEI); same benefits; hyperkalemia |
| CCB (DHP) | Nifedipine, Amlodipine | Block L-type Ca2+ channels → vasodilation | Reflex tachycardia, peripheral edema, flushing |
| CCB (Non-DHP) | Verapamil, Diltiazem | Same; also ↓ HR + ↓ contractility | Bradycardia, constipation (verapamil), HF risk |
| Thiazide Diuretic | Hydrochlorothiazide | ↓ Na+/Cl- reabsorption (DCT) | Hypokalemia, hyperuricemia/gout, hyperglycemia, hypercalcemia |
| Loop Diuretic | Furosemide | ↓ Na+/K+/2Cl- reabsorption (loop) | Hypokalemia, ototoxicity (high dose), dehydration |
| K+-sparing | Spironolactone | Aldosterone antagonist | Hyperkalemia, gynecomastia (spironolactone) |
| β-blocker | Metoprolol, Propranolol | β-receptor block | Bradycardia, fatigue, bronchospasm (non-selective) |
| α1-blocker | Prazosin | α1 block | Orthostatic hypotension, reflex tachycardia |
| Central α2-agonist | Clonidine, Methyldopa | α2 agonism → ↓ sympathetic outflow | Sedation, dry mouth, rebound hypertension |
| Direct Vasodilator | Hydralazine | Direct arteriolar dilation | Reflex tachycardia, lupus-like syndrome |
| Direct Renin Inhibitor | Aliskiren | Bind renin, inhibit its activity | Diarrhea; ↑ risk of adverse events vs ACEI/ARB |
Part C: Anti-anginal Drugs
| Drug Class | MOA | Effect | Key Point |
|-----------|-----|--------|-----------|
| Nitrates (Nitroglycerin) | Donate NO → ↑ cGMP → vasodilation (more vein) | ↓ Preload → ↓ O2 demand | Tolerance (tachyphylaxis) with continuous use; nitrate-free interval needed |
| β-blockers (Propranolol) | ↓ HR, ↓ contractility | ↓ O2 demand | Primary therapeutic action = ↓ myocardial O2 requirement |
| CCBs (Verapamil, Nifedipine) | ↓ HR (non-DHP) or vasodilation (DHP) | ↓ O2 demand or ↑ O2 supply | Verapamil + β-blocker = dangerous (additive bradycardia/AV block) |
Combination Therapy for Angina
| Combination | Benefit | Risk |
|-------------|---------|------|
| Nitrate + β-blocker | β-blocker counteracts reflex tachycardia from nitrate | — |
| Verapamil + β-blocker | — | Aggravated AV block + HF (AVOID) |
Part D: CHF Drugs — Mortality Benefit
| Drug | Effect on Mortality | Mechanism |
|------|-------------------|-----------|
| ACEI/ARB | ↑ Survival | ↓ Remodeling, ↓ afterload |
| β-blockers (Carvedilol, Metoprolol) | ↑ Survival | ↓ Sympathetic overdrive, ↓ remodeling |
| Spironolactone | ↑ Survival | ↓ Aldosterone → ↓ fibrosis |
| Digoxin | ↓ Symptoms, no mortality benefit | ↑ Contractility |
| Milrinone (PDE inhibitor) | ↑ Mortality (not recommended) | ↑ cAMP → arrhythmias |
Exam-Frequency Core Points (from exam notes)
High-Yield Points
- ACE inhibitors (lisinopril): first-line for HTN + diabetes/CKD — cough side effect
- ARBs (losartan): ACEi alternative — no cough
- CCBs: dihydropyridines (amlodipine) = vasodilation; non-DHP (verapamil) = rate control
- β-blockers (metoprolol): ↓ HR, ↓ contractility — first-line for angina, post-MI
- Thiazide diuretics (HCTZ): first-line for uncomplicated HTN
- Nitrates (nitroglycerin): venodilators → ↓ preload → angina relief
- Digoxin: positive inotrope for CHF + rate control for AFib (narrow TI)
Topic Summary
ACE inhibitors/ARBs are first-line for hypertension (especially with diabetes, CKD). CCBs cause vasodilation (dihydropyridines like nifedipine) or heart rate reduction (verapamil, diltiazem). β-blockers reduce cardiac output. Thiazide diuretics are first-line for uncomplicated hypertension.