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Commonly Used drugs for the treatment of Hypertension Drug Class Prototype Drug ACE Inhibitors Captopril Lisinopril Enalipiril Losartan Angiotensin II receptor Antagonists Calcium Channel Antagonists Beta Antagonists Nifedipine Verapamil, diltiazem, Propranolol Metoprolol Diuretics Thiazides, Spironolactone Furosemide Vasodilators Hydralazine Minoxidil Na+ nitroprusside Central Agonists Alpha Antagonists Clonidine Dopamine Agonist Fenoldopam Prazosin Mechanism of Action Inhibits ACE - ↓ angiotensin II, ↑ bradykinin Blocks angiotensin II receptor binding Hemodynamic Effects Adverse Drug Effects ↓ systemic vascular resistance and preload Bind Ca2+ channels ↓ Ca2+ for muscle contraction Non-selective β receptor blockade Cardioselective β1 receptor blockade Vasodilation HTN w/1st dose, Cough & angioedema w/↑ kinin, renal impairment, hyperkalemia, no cough renal impairment, hyperkalemia, Constipation, peripheral edema, worsen CHF, headache Negative salt and water balance, ↑PGI2 synthesis & action, vasodilaton Early drop in CO due to ↓volume Peripheral vascular resistance decreased Relax vascular smooth muscle ? Vasodilation - ↑ K+ channel hyperpolarize SM Causes NO release, relaxes SM Central α2a recptor stimulation Block peripheral α1 adrenoreceptors ↓ systemic vascular resistance ↓ systemic vascular resistance Bad dreams, depression Cardio – worsen CHF and occlusive peripheral vascular disease (OPVD) Lungs – bronchospasm Fluid and electrolyte imbalance, particularly hypokalemia with thiazides and loop diuretics, Hyperkalemia with spironolactone Furosemide mostly for fluid management Immuno – lupus like Sx Cardio - ↑ HR use β block Cardio - ↑ HR use β block Fluid retention, Hypertrichosis ↓ cardiac preload and afterload ↓ CO, ↓ systemic vascular resistance ↓ systemic vascular resistance Hypotension, cyanide and thiocyanate poisoning Short ½life. Missed dose = rebound HTN Orthostatic HTN w/1st dose. Give 1st HS. Dopamine (DA) 1 agonist ↑ renal blood flow ↑Na+ excretion Vasodilation w/↓ preload ↓afterload ↓ Heart rate and contractility, ↑ systemic vascular resistance Drug-Drug Interactions NSAIDS, Lithium Drug-Disease Interactions Pregnancy NSAIDS, Lithium Pregnancy Digoxin, β blockers = A-V block May interact w/CCBs or digoxin causing A-V block Unstable angina, MI, HTN? NSAIDS, Lithium Chronic kidney disease Asthma, COPD, severe heart failure, OPVD, high° A-V block Kidney or liver disease Depression, sexual dysfunction HF IV only BP classification Normal Pre-Hypertension Stage 1 Hypertension Systolic BP, mmHg <120 and 120-130 or 140-159 or Diastolic BP, mmHg <80 80-89 90-99 Lifestyle Modification Encourage Yes Yes Without Compelling Indication With Compelling Indications No antihypertensive drug indicated Drug(s) for the compelling indications Thiazide-type diuretics for most; may Drug(s) for the compelling indications condsider ACE inhibitor, β-blocker, Other antihypertensive drugs diuretics, ACE CCB or combination inhibitor, ARB, β-blocker, CCB as needed. Stage 2 Hypertension ≥160 or ≥100 Yes 2-Drug combination for most Drug(s) for the compelling indications (usually thiazide-type diuretic and Other antihypertensive drugs diuretics, ACE ACE inhibitor, or ARB or β-blocker inhibitor, ARB, β-blocker, CCB as needed. or CCB) Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CCB, calcium channel blocker. Condition Diuretic Heart Failure Post-MI High coronary disease risk Diabetes Chronic Kidney Disease Recurrent stroke prevention ☺ ☺ ☺ ☺ ΒBlocker ☺ ☺ ☺ ☺ ACE Inhibitor ☺ ☺ ☺ ☺ ☺ ☺ ARB CCB ☺ ☺ ☺ ☺ ☺ Aldosterone Antagonist ☺ ☺