Cardiovascular Drugs for Pharmacology Final

Cardiovascular Drugs for Pharmacology Final

Name / Class/MOA / Clinical Use / Toxicity/Contraindications / Other /
a-methyldopa / Prodrug, →a-methylNE, an a2 agonist that↓’s CNS symp. outflow / Treat HTN (second line) / Don’t give i.v., or will cause ↑BP due to action on vascular a2R’s. CNS effects: sedation, fatigue, dry mouth, sexual dysfunction. Hemolytic anemia. / Not widely used anymore due to CNS side effects.
Amiodarone / K+ channel blocker; also blocks Na+ channels and β receptors. / Class III anti-arrhythmic drug. DOC to terminate A-fib, 2nd choice for prevention. DOC to suppress or prevent V-tach. / NO drug-induced proarrhythmia!
Variable effects on thyroid function because it is iodinated; some pulmonary toxicity.
↑levels of warfarin and digoxin with amiodarone – often used in same patients! / Short-term i.v., or long-term oral treatment. Prolongs Q-T interval. Good for pts. w/ CHF or post-infarct.
Amlodipine / L-type Ca++-channel blocker; Strong arteriolar vasodilation is main effect. / A DOC for prophylaxis of variant angina / Contraindicated if already significant hypotension; Don’t mix w/other vasodilators.
Reflex tachycardia (serious), headache, edema. / Strongest vascular effects of the Ca++ blockers (w/nifedipine).
Atenolol / β-blocker / Treat HTN, angina / This one not really covered…
Atorvastatin
(Lipitor®) / HMG-CoA reductase inhibitor; inhibits rate-limiting step in cholesterol synthesis, up-regulates hepatic LDL receptors, so↓LDL / Treat hyperlipidemia (first-line for lowering LDL) / Contraindicated in active or chronic liver disease, pregnancy.
Myopathy,↑liver transaminases. / Reduces risk for acute coronary syndromes and stroke.
Captopril / ACE inhibitor; active drug, competitive;↓angiotensin II and aldosterone, so↓PVR and inhibits AT-mediated hypertrophy; / 1st line treatment of CHF and HTN
Also beneficial effects on serum lipids. / Persistent cough, angioedema.
May↓renal fxn, so don’t use if renal artery stenosis.
Little effect on heart rate (no reflex tachycardia). / Kidney response to lowered BP is blocked, so diuretics not required with ACE inhibitors.
Carvedilol / a1, β1 and β2 blocker; (racemic mixture);↓PVR,↑regulates β receptors in heart. Also↓LVH. / Treat mild-to-moderate CHF, HTN, ischemic heart disease. / Same side effects as propranolol. / Positive effects on lipid profiles
Cholestyramine / Bile acid sequestrant (resin); moderately lowers LDL cholesterol / Treat hyperlipidemia / Little systemic availability, so low toxicity.
Contraindicated if TG > 400 mg/dL (may↑more) / Often combined w/other lipid-lowering drugs.
Clofibrate / Fibrate – ligand for nuclear receptor controlling FA metabolism; effective in reducing TG levels (↓40%) / Treat hyperlipidemia / Risk of gallstones.
Risk of myopathy when comb. w/statin.
Contraindicated w/ hepatic or renal insufficiency.
Clonidine / a2 agonist that↓’s CNS symp. outflow (“sympatholytic”) / Treat HTN (second line) / Sedation, fatigue, dry mouth, sexual dysfunction. / Apraclonidine = ocular form,↓aqueous humor
Digoxin / Cardiac glycoside, inhibits myocardial Na+-K+ ATPase (competitive inh. of K+), causes↑intracell. Na+, inhibiting exchange of Na+ (in) for Ca++ (out), so ↑intracellular Ca++ (positive inotropism) Slows SA and AV nodal conduction. / Treat CHF,
Anti-arrhythmic
(for supraventricular tachyarrhythmias)
Limited therapeutic index. / N/V, visual disturbances, various arrhythmias.
Renal disease ↓’s clearance, may lead to toxic buildup. Amiodarone, quinidine and verapamil↓renal clearance of digoxin. Cholestyramine ↓’s bioavailability. Hypokalemia ↑’s likelihood of toxicity (beware diuretics!). Hypoxia also ↑’s toxicity. Elderly more sensitive! / Variable GI absorption.
Excreted unchanged by kidney.
t½ = 36-48h
Treat toxicity w/ phenytoin, lidocaine, K+, Fab fragments to digoxin.
Digitoxin / Same as digoxin, except: 90-100% GI absorption; Hepatic metabolism, renal excretion.; t½ = 4-6 days
Diltiazem / L-type Ca++-channel blocker; moderate↓in cardiac contraction, slowed conduction @ SA and AV nodes, moderate vasodilation (art.) / A DOC for prophylaxis of variant angina / See others / Intermediate cardiac & vascular effects (compare other Ca++ blockers.)
Dipyridamole / Phosphodiesterase (PDE) inhibitor; ↑cAMP, inhibits platelet activation, promotes arterial relaxation / Prevents clot formation; Therarpy for MI, angina; / Adjunct for anticoagulation therapy.
Dobutamine / β1 & β2 agonist,↑force of myocardial contraction. / Treat cardiogenic shock, CHF / Long term use can cause downregulation & desensitization of receptors. Give i.v. only. / Racemic mixture, is a1 agonist & antagonist, too.
Enalapril / ACE inhibitor; prodrug, metabolized to active enalaprilat. / Same as captopril…
Flecainide / Na+ channel blocker (strongest!) / Class IC
anti-arrhythmic drug – a DOC for prophylaxis of A-fib. / Relatively high incidence of proarrhythmia – contraindicated with structural heart disease (ischemic damage or hypertrophy). Also avoid with depressed ventricular fxn (↓ejection fraction). / Significantly widens QRS
Furosemide / Loop diuretic (sulfonamide): inhibits Na/K/2Cl transporter in TALH cells, ↑ GFR / Treat HTN / Alkalosis, hypokalemia (beware digoxin/digitoxin!), hypovolemia, dehydration, shock. CN VIII damage (deafness). / In CHF, even before diuresis, eases breathing,↓pulmonary resistance and pulmonary artery BP.
Gemfibrozil / Fibrate – see clofibrate
Guanethidine / Sympatholytic, inhibits Ca++-dependent release of NE in periphery / Treat HTN / Hypotension, bradycardia. / Not widely prescribed – “historical interest”.
Hydralazine / Arterial selective vasodilator;
↑’s smooth muscle levels of cGMP; result is ↓PVR,↓cardiac afterload, ↑ cardiac output. / Treat CHF and HTN / Lupus-like symptoms, headache, reflex tachycardia (blocked by co-administered β-blockers), water and salt retention (co-administer diuretics). / Use is decreasing due to safer, more effective drugs (ACE inhibitors and AT-R antagonists)
Hydrochlorothiazide / Thiazide diuretic, ↓s plasma volume and↓s PVR long-term. / Treat HTN, often in combination w/other antihypertensives. / Hypokalemia, may cause ventricular arrhythmias (not a major impediment to therapeutic use). / Especially effective in African Americans and the elderly.
Inamrinone
(previously amrinone) / PDE inhibitor (cardiac/vascular isoform); effectively ↑’s cAMP levels,↑cardiac output,↓PVR; / Short-term treatment of CHF. (Positive inotropic agent). / Potential to induce arrhythmias, thrombocytopenia, nausea/vomiting.
Reserved for patients who don’t respond to vasodilators or other positive inotropic agents. / NOT effective in reducing morbidity and mortality a/w heart failure
Isoproterenol / β1 & β2 agonist
(more affinity than Epi or NE) / VERY low affinity for a receptors (“pure β-ag”)
Isosorbide dinitrate / Organic nitrate, slow onset, medium duration↓’s preload on heart due to vasodilation of large veins. / 2nd choice for angina prophylaxis / Headache, hypotension, reflex tachycardia. Nitrate tolerance with continuous exposure.
Don’t combine w/sildenafil (Viagra®)!
Labetalol / a1, β1 and β2 blocker / Treat HTN
Lidocaine / Na+ channel blocker
(weakest, safest). / Class IB
anti-arrhythmic drug. / Some risk of proarrhythmia
(less than other Na+ blockers). / Minimal effect on ECG. Parenteral use only.
Losartan / Competitive angiotensin II (AT1) receptor antagonist; inhibits vasoconstriction, aldosterone release and hypertrophic growth. / 1st line treatment of CHF and HTN / Fewer side effects than ACE inhibitors. / Diuretics not required.
Lovastatin / HMG-CoA reductase inhibitor / See atorvastatin
Metoprolol / Selective β1 blocker / Like propranolol, but without β2-mediated side effects.
Milrinone / PDE inhibitor / Like inamrinone, but with less toxicity.
Minoxidil / Primarily an arterial vasodilator by↑cGMP, stim. outward K+ channels, hyperpolarizes vascular sm. muscle. / Reserved for treatment of moderate to severe HTN. / Headache, hypotension, reflex tachycardia (counter w/β-blockers), edema (counter w/diuretics). Reflexes may blunt effect of ↓PVR. / Also causes hair growth (marketed as Rogaine®)
Nadolol / β-blocker / Treat HTN, angina / This one not really covered…
Nicotinic acid (niacin) / Decreases fatty acid mobilization from adipose to liver.↓plasma TG,↓VLDL and LDL and ↑HDL. / Treat hyperlipidemia; Most effective at raising HDL levels. / Glucose intolerance (avoid high doses w/type 2 DM), hepatotoxicity, hyperuricemia: contraindicated w/severe liver disease or gout.
Nifedipine / L-type Ca++-channel blocker; Strong arteriolar vasodilation is main effect. / A DOC for prophylaxis of variant angina / Contraindicated if already significant hypotension; Don’t mix w/other vasodilators.
Reflex tachycardia (serious), headache, edema.
Use extended release formulation. / Strongest vascular effects of the Ca++ blockers (w/amlodipine).
Nitroglycerin / Organic nitrate, ↓’s preload on heart due to vasodilation of large veins. / Sublingual = DOC to terminate anginal episode (stable or variant)
Patch = 2nd choide for angina prophylaxis / Headache, hypotension, reflex tachycardia. Nitrate tolerance with continuous exposure (i.e., with patch).
Don’t combine w/sildenafil (Viagra®)! / Translingual spray or sublingual tab = rapid onset, short DOA;
Patch = slow onset, long DOA
Nitroprusside
(sodium nitroprusside) / Balanced vasodilator; ↑’s smooth muscle levels of cGMP; result is
↓ cardiac preload and afterload,
↑ cardiac output, ↓ pulmonary congestion. / Acute management of CHF.
Useful in hypertensive emergencies (diastolic BP > 120 w/ end-organ damage). / Hypotension, risk of cyanide poisoning w/high concentrations (it is metabolized to cyanide). / Unstable in solution, ultra-short DOA
Phenylephrine / Prototype a1 agonist, causes vasoconstriction / Hemorrhage control, treatment of hypotension. / Less potent than Epi or NE, but orally active and longer t½
Pindolol / β-blocker with intrinsic sympathomimetic activity (ISA)
(partial agonist) / Treat HTN / Masks hypoglycemic emergency (prevents tachycardia) in diabetics, exacerbates AV node block. / Blocking effect predominates over ISA as endog. NE is released.
Prazosin / Selective a1 antagonist (competitive),↓TPR & venous return / Treat HTN / Renal reflex may → fluid retention, so give diuretic too. Orthostatic hypotension and 1st dose syncope. / ↓BP does NOT cause reflex tachycardia.
Propranolol / Non-selective β-blocker (β1 & β2); ↓’s HR and force of contraction, so ↓’s O2 demand of heart.
Slows conduction @ AV node. / DOC for prophylaxis of stable angina and ischemia relief during acute coronary syndromes; also for HTN. Class II anti-arrhythmic drug (DOC for ventricle rate control w/A-fib). / Contraindicated (due to β2 block) in patients with COPD (asthma) or peripheral vascular disease.
Also masks hypoglycemic emergency (prevents tachycardia) in diabetics, exacerbates AV node block (due to β1-block). “Withdrawal syndrome” possible, →tachycardia… so↓dose gradually. / A DOC for supraventricular tachyarrhythmias (A-fib.), but secondary choice for V-tach.
Quinidine / Blocks Na+ and delayed rectifying K+ channels. Slows conduction through ventricles and prolongs ventricular action potential. / Class IA
anti-arrhythmic drug. / Risk of drug-induced arrhythmias (torsades de pointe), cinchonism (tinnitus, visual disturbances and anticholinergic effects), negative inotropic effect.
↑digoxin levels and ↓elimination of same – can be life-threatening! / Widens QRS complex (Na+ block) and lengthens Q-T interval (K+ block)
Reserpine / Sympatholytic, depletes NE from nerve endings in CNS & periphery. / Treat HTN / Hypotension (↓PVR and CO), insomnia, sedation, depression / Not widely prescribed – “historical interest”.
Sotalol / K+ channel blocker; also blocks β1 and β2- receptors. / Class III (and II) anti-arrhythmic drug. DOC for prophylaxis of A-fib. / Significant risk of drug-induced arrhythmias (torsades de pointe) – incidence 2-4%.
Beware β2 effects with asthma, etc.
Could aggravate CHF (β1-block, negative inotropism). / Prolongs Q-T interval. Good for patients w/ischemic heart disease due to β-block.
Streptokinase / Binds, activates plasminogen (without cleavage)→fibrinolysis. / Clot buster for acute MI, DVT, multiple PE / Bleeding! / Aprotinin may be used as antidote for excess bleed.
Sulfinpyrazone / Uricosuric agent: why is it on the cardiovascular drug list???
Verapamil / L-type Ca++-channel blocker;
Strong inhibition of cardiac contractility and conduction across SA and AV nodes. / A DOC for prophylaxis of variant angina.
Class IV anti-arrhythmic drug.
DOC for ventricular rate control in A-fib. / Don’t combine w/other drugs that ↓cardiac fxn! (β-blockers, digoxin). Avoid w/CHF, SA or AV node block, or hypotension. Side effects include hypotension, bradycardia, AV node block. / Strongest cardiac effects of the Ca++ blockers.
Prolongs P-R interval.