Antihypertensive Drugs

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### Introduction to Hypertension - **Definition:** Persistently elevated arterial blood pressure. - **Normal BP:** <120/80 mmHg - **Elevated BP:** 120-129/<80 mmHg - **Hypertension Stage 1:** 130-139/80-89 mmHg - **Hypertension Stage 2:** $\ge$140/$\ge$90 mmHg - **Goal:** Reduce cardiovascular morbidity and mortality. ### Thiazide Diuretics (e.g., Hydrochlorothiazide, Chlorthalidone) - **Mechanism of Action (MOA):** - Inhibit Na+/Cl- cotransporter in distal convoluted tubule. - Increases Na+, Cl-, and water excretion. - Initially decreases blood volume, then reduces peripheral vascular resistance. - **Indications:** First-line for most uncomplicated hypertension, heart failure, edema. - **Side Effects:** - Hypokalemia, hyponatremia, hypercalcemia, hyperuricemia (gout), hyperglycemia. - Photosensitivity, erectile dysfunction. - **Contraindications:** Anuria, severe renal impairment, sulfa allergy. ### ACE Inhibitors (ACEIs) (e.g., Lisinopril, Enalapril, Ramipril) - **MOA:** - Inhibit Angiotensin-Converting Enzyme (ACE). - Prevents conversion of Angiotensin I to Angiotensin II (potent vasoconstrictor). - Reduces aldosterone secretion (less Na+ and water retention). - Decreases bradykinin breakdown (vasodilator). - **Indications:** Hypertension, heart failure, post-MI, diabetic nephropathy. - **Side Effects:** - Dry cough (due to bradykinin), angioedema (rare but serious). - Hyperkalemia, acute kidney injury (especially in bilateral renal artery stenosis). - Hypotension. - **Contraindications:** Pregnancy (teratogenic), bilateral renal artery stenosis, history of angioedema. ### Angiotensin Receptor Blockers (ARBs) (e.g., Losartan, Valsartan, Candesartan) - **MOA:** - Block Angiotensin II from binding to AT1 receptors. - Similar effects to ACEIs but do not increase bradykinin. - **Indications:** Hypertension, heart failure, diabetic nephropathy (especially if ACEI intolerant). - **Side Effects:** - Hyperkalemia, acute kidney injury. - Less cough and angioedema than ACEIs. - Hypotension. - **Contraindications:** Pregnancy (teratogenic), bilateral renal artery stenosis. ### Beta-Blockers (e.g., Metoprolol, Atenolol [cardioselective]; Propranolol, Labetalol [non-selective]) - **MOA:** - Block $\beta_1$-adrenergic receptors in heart (↓ HR, ↓ contractility, ↓ renin release). - Non-selective block $\beta_2$ receptors (bronchoconstriction, peripheral vasoconstriction). - **Indications:** Hypertension (especially with co-existing CAD, heart failure, migraine), angina, arrhythmias. - **Side Effects:** - Bradycardia, fatigue, dizziness, erectile dysfunction. - Bronchospasm (non-selective), masking of hypoglycemia symptoms. - Worsening of peripheral vascular disease. - **Contraindications:** Severe bradycardia, heart block ($\gt$1st degree), decompensated heart failure, severe asthma/COPD (non-selective). ### Calcium Channel Blockers (CCBs) #### Dihydropyridines (e.g., Amlodipine, Nifedipine) - **MOA:** Block L-type Ca2+ channels primarily in vascular smooth muscle $\rightarrow$ vasodilation. - **Indications:** Hypertension, angina, Raynaud's phenomenon. - **Side Effects:** Peripheral edema, headache, flushing, reflex tachycardia (less common with amlodipine). #### Non-Dihydropyridines (e.g., Verapamil, Diltiazem) - **MOA:** Block L-type Ca2+ channels in heart and vascular smooth muscle $\rightarrow$ ↓ HR, ↓ contractility, vasodilation. - **Indications:** Hypertension, angina, arrhythmias (e.g., atrial fibrillation rate control). - **Side Effects:** Bradycardia, AV block, constipation (verapamil), gingival hyperplasia. - **Contraindications (both):** Severe hypotension, sick sinus syndrome (non-dihydropyridines), decompensated heart failure (non-dihydropyridines). ### Alpha-Blockers (e.g., Prazosin, Doxazosin, Terazosin) - **MOA:** Block $\alpha_1$-adrenergic receptors on vascular smooth muscle $\rightarrow$ vasodilation. - **Indications:** Hypertension (often add-on), Benign Prostatic Hyperplasia (BPH). - **Side Effects:** First-dose phenomenon (orthostatic hypotension/syncope), dizziness, headache, palpitations. - **Contraindications:** Volume depletion. ### Direct Vasodilators (e.g., Hydralazine, Minoxidil) - **MOA:** Directly relax arterial smooth muscle. - **Indications:** Severe hypertension, hypertensive emergencies (hydralazine), refractory hypertension (minoxidil). - **Side Effects:** - Hydralazine: Reflex tachycardia, fluid retention, headache, drug-induced lupus syndrome. - Minoxidil: Reflex tachycardia, fluid retention, hypertrichosis (hair growth). - **Administration:** Often given with a beta-blocker and diuretic to counteract reflex effects. ### Central Alpha-Agonists (e.g., Clonidine, Methyldopa) - **MOA:** Stimulate $\alpha_2$-adrenergic receptors in brainstem $\rightarrow$ ↓ sympathetic outflow from CNS $\rightarrow$ ↓ HR, ↓ peripheral resistance. - **Indications:** Hypertension (often as add-on or specific situations like pregnancy - methyldopa). - **Side Effects:** Sedation, dry mouth, constipation, rebound hypertension if abruptly discontinued. - **Considerations:** Methyldopa can cause hemolytic anemia and liver dysfunction. ### Aldosterone Antagonists (e.g., Spironolactone, Eplerenone) - **MOA:** Block aldosterone receptors in collecting duct $\rightarrow$ ↑ Na+ and water excretion, ↓ K+ excretion. - **Indications:** Hypertension (especially with primary aldosteronism or resistant hypertension), heart failure, edema. - **Side Effects:** Hyperkalemia, gynecomastia (spironolactone), sexual dysfunction. - **Contraindications:** Hyperkalemia, severe renal impairment.