Cardiovascular Pharmacology Flashcards
Cardiovascular Pharmacology
Treatment of primary (essential) hypertension)
Thiazides, ACE inhibitors, ARBs, dihydropyridine Ca2+ chanel blockers
Cardiovascular Pharmacology
Treatment of hypertension with heart failure
Diuretics, ACE inhibitors/ARBs, β blockers (compensated HF), aldosterone antagonists
Cardiovascular Pharmacology
Treatment of hypertension with diabetes mellitus
ACE inhibitors/ARBs, Ca2+ channel blockers, thiazide diuretics, β blockers
Cardiovascular Pharmacology
Treatment of hypertension in pregnancy
Hydralazine, labetalol, methyldopa, nifedipine
Cardiovascular Pharmacology
Calcium channel blockers
Examples: amlodipine, clevidipine, nicardipine, nimodipine (dihydropyridines, act on vascular smooth muscle); diltiazem, verapamil (non-hdihydropyridines, act on heart)
Mechanism: Block voltage-dependent L-type calcium channels of cardiac and smooth muscle → ↓ muscle contractility
Vascular smooth muscle: amlodipine = nifedipine > diltiazem > verapamil
Heart: verapamil > diltiazem > amlodipine = nifedipine
Clinical Use:
Dihydropyridine (except nimodipine): hypertension, angina (including Prinzmetal), Raynaud phenomenon
Nimodipine: SAH (prevents cerebral vasospasm)
Clevidipine: Hypertensive urgency or emergency
Non-dihydropyridine: Hypertension, angina, atrial fibrillation/flutter
Adverse Effects:
Non-dihydropyridine: cardiac depression, AV block, hyperprolactinemia, constipation
Dihydropyridine: Peripheral edema, flushing, dizziness, gingival hyperplasia
Cardiovascular Pharmacology
Hydralazine
MOA: ↑ cGMP → smooth muscle relaxation. Vasodilates arterioles > veins; afterload reduction
Clinical Use: Severe hypertension (particularly acute), HF (with organic nitrate). Safe to use during pregnancy. Frequently coadministered with a β-blocker to prevent reflex tachycardia.
Adverse effects: Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, headache, angina. Lupus-like syndrome.
Cardiovascular Pharmacology
Treatment of hypertensive emergency
Celvidipine, fenoldopam, labetalol, nicardipine, nitroprusside
Cardiovascular Pharmacology
Nitroprusside
MOA: Short acting; ↑ cGMP via direct release of NO.
Use: Hypertensive emergency
Adverse Effects: Can cause cyanide toxicity (releases cyanide)
Cardiovascular Pharmacology
Fenoldopam
MOA: Dopamine D1 receptor agonist - coronary, peripheral, renal, and splanchnic vasodilation → ↓ BP, ↑ natriuresis.
Use: Hypertensive emergency, postoperative antihypertensive.
Adverse Effects: Hypotension and tachycardia
Cardiovascular Pharmacology
Nitrates (nitroglycerin, isosorbide dinitrate, isosorbide mononitrate)
MOA: Vasodilate by ↑ NO in vascular smooth muscle → ↑ in cGMP & smooth muscle relaxation. Dilate veins»_space; arteries. ↓ Preload.
Use: Angina, acute coronary syndrome, pulmonary edema.
Adverse Effects: Reflex tachycardia (treat with β-blockers), hypotension, flushing, headache, “Monday disease in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend → tachycardia, dizziness, headache upon reexposure
Cardiovascular Pharmacology
Effects of nitrates on angina
↓ EDV ↓ BP No change in contractility ↑ HR (reflex response) ↓ Ejection time ↓ MVO2
Cardiovascular Pharmacology
Effects of β-blockers on angina
No effect or ↑ EDV ↓ BP ↓ Contractility ↓ HR ↑ Ejection time ↓ MVO2
Cardiovascular Pharmacology
Effects of nitrates + β-blockers on angina
No effect or ↓ EDV ↓ BP Little/no effect on contractility ↓ or no effect on HR Little or no effect on ejection time ↓↓ MVO2
Cardiovascular Pharmacology
Ranolazine
MOA: Inhibits late phase of sodium current → ↓ diastolic wall tension and O2 consumption. No effect on HR or contractility
Use: Angina refractory to other medical therapies
Adverse Effects: Constipation, dizziness, headache, nausea, QT prolongation
Cardiovascular Pharmacology
HMG-CoA reductase inhibitors (lovastatin, pravastatin)
MOA: Inhibition of HMG-CoA to mevalonate, a cholesterol precursor ; ↓ mortality in CAD patients
↓↓↓ LDL
↑ HDL
↓ TG
Adverse Effects: Hepatotoxicity (↑ LFTs), myopathy (esp. when used with fibrates or niacin)
Cardiovascular Pharmacology
Bile acid resins (cholestyramine, colestipol, colesevelam)
MOA: Prevents intestinal reabsorption of bile acids; liver must use cholesterol to make more
↓↓ LDL
Slightly ↑ HDL
Slightly ↑ TG
Adverse Effects: GI upset, ↓ absorption of other drugs and fat-soluble vitamins
Cardiovascular Pharmacology
Ezetimibe
MOA: Prevent cholesterol absorption at small intestine brush border
↓↓ LDL
No effect on HDL or TG
Adverse effects: Rare ↑ LEFTs, diarrhea
Cardiovascular Pharmacology
Fibrates (gemfibrozil, bezafibrate, fenofibrate)
MOA: Upregulate LPL → ↑ clearance; activates PPAR- α to induce HDL synthesis
↓ LDL
↑ HDL
↓↓↓ TG
Adverse Effects: Myopathy, (↑ risk with statins), cholesterol gallstones
Cardiovascular Pharmacology
Niacin (vitamin B3)
MOA: Inhibits lipolysis (hormone-sensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis
↓↓ LDL
↑↑ HDL
↓ TG
Adverse Effects: Red flushed face, which is ↓ by NSAIDs or long-term use, hyperglycemia, hyperuricemia
Cardiovascular Pharmacology
Digoxin
MOA: Direct inhibition of Na+/K+ ATPase → indirect inhibition of Na+/Ca2+ exchanger → ↑[Ca2+]i → positive inotropy. Stimulates vagus nerve → ↓ HR.
Use: HF; atrial fibrillation (↓ conduction at AV node and depression of SA node)
Adverse Effects: Cholinergic (nausea, vomiting, diarrhea, blurry yellow vision, arrhythmias, AV block), hyperkalemia.
Toxicity Risk Factors: Renal failure, hypokalemia, drugs that displace digoxin from tissue-binding sites, and ↓ clearance.
Antidote: Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+
Cardiovascular Pharmacology
Class IA antiarrhythmics (quinidine, procainamide, disopyramide)
MOA: Sodium channel blocker. Slow or block conduction. ↓ slope of phase 0 depolarization → ↑ AP duration, ↑ ERP, ↑ QT interval
Use: Atrial & ventricular arrhythmias, especially re-entrant and ectopic SVT and VT
Adverse Effects: Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), heart failure (disopyramide), thrombocytopenia, torsades de pointes due to ↑ QT interval
Cardiovascular Pharmacology
Class IB antiarrhythmics (lidocaine, mexiletine)
MOA: Sodium channel blocker. Slow or block conduction. ↓ slope of phase 0 depolarization → ↓ AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue.
Use: Acute ventricular arrhythmias (especially post-MI), digitalis-induced arrhythmias.
Adverse Effects: CNS stimulation/depression, cardiovascular depression
Cardiovascular Pharmacology
Class IC antiarrhythmics (flecainide, propafenone)
MOA: Sodium channel blocker. Slow or block conduction. ↓ slope of phase 0 depolarization → significantly prolong ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration
Use: SVTs, including atrial fibrillation. Only as a last resort in refractory VT.
Adverse Effects: Proarrythmic, especially post-MI
Cardiovascular Pharmacology
Class II antiarrhythmics (metoprolol, propanolol, esmolol, atenolol, timolol, carvedilol)
MOA: β-blockers. ↓ SA & AV nodal activity by ↓ cAMP, ↓ Ca2+ currents. Suppress abnormal pacemakers by ↓ slope of phase 4. AV node particularly sensitive → PR interval. Esmolol very short acting.
Use: SVT, ventricular rate control and atrial flutter.
Adverse effects: Impotence, exacerbation of COPD and asthma, CV effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Can cause unopposed α1-agonism if given alone for pheochromocytoma or cocaine toxicity. Metoprolol: dyslipidemia. Propanalol: exacerbate vasospasm in Prinzmetal angina.
Tx of overdose: saline, atropine, glucagon
