Cardiac Pharmacology Update

1. Cardiac Pharmacology Update 2011 Cardiac Issues Nursing Breakout Session Lani Steltz, PharmD. Pharmacist Yakima Regional Medical Center

2. Outline • Common Cardiac Medications by Class • Examples • Mechanism of Action (MOA) • Side Effects • Common Interactions • Questions

3. Angiotensin Converting Enzyme Inhibitors (ACE-I) • Examples: • Enalapril (Vasotec), Lisinopril (Prinivil/Zestril), Captopril (Capoten), Benazepril (Lotensin), Fosinopril (Monopril), Quinapril (Accupril), Ramipril (Altace) • MOA: • suppresses the renin-angiotensin-aldosterone system; prevention of the conversion of Angiotensin I (AT I) to Angiotensin II (AT II, which is a vasoconstrictor) • Vasodilation (↓ afterload, ↓ BP); • Prevents cardiac remodeling after MI (prevent development heart failure); Renal protective in DM • Side Effects: • ↓BP, ↑ K+, Cough, Angioedema, ↑ SCr & BUN, neutropenia, hepatotoxicity; teratogenic

4. Angiotensin Receptor Blockers (ARB) • Examples: • Candesartan (Atacand), Irbesartan (Avapro), Losartan (Cozaar), Olmesartan (Benicar), Telmisartan (Micardis), Valsartan (Diovan) • MOA: • blocks Angtiotensin II, a vasoconstrictor, at the receptor sites, effect similar to ACE I • Vasodilation (↓ afterload, ↓ BP); Prevents cardiac remodeling after MI (prevent development heart failure); Renal protective in DM • Side Effects: • ↓BP, ↑ K+, ↑ SCr & BUN, teratogenic • Same as ACE-I, except w/o cough

5. Beta Blockers (BB) • Examples: • Selective BB • Metoprolol (Lopressor/Toprol XL), Atenolol (Tenormin), Betaxolol (Corgard), Bisoprolol (Zebeta), Nebivolol (Bystolic) • Non-Selective BB • Propranolol (Inderal), Labetalol (Trandate), Carvedilol (Coreg), Nadolol (Corgard) • MOA: ↓HR, ↓BP, and ↓ force of contraction • Selective BB block the beta1 adrenergic receptors of the heart—blocking of catecholemines • Non-Selective BB blocks both beta1 receptors (heart) and beta2 receptors (bronchial and vasculature sites)

6. Beta Blockers (BB) • Side Effects: • bradycardia, hypotension, masks symptoms of hypoglycemia, fatigue, lethargy, wheezing/dyspnea nightmares, insomnia, impotence • Non-Selective BB: • Bronchospasm and vasoconstriction • Use w/ caution in asthma, COPD, PVD, DM

7. Calcium Channel Blocker (CCB) • Examples: • Non-Dihydropyridines—Verapamil (Calan/Covera/Verelan/Isoptin), Diltiazem (Cardizem/Tiazac/Diltia/Cartia/Diltzac/Dilacor); • Dihydropyridines—Amlodipine (Norvasc), Felodipine (Plendil), Isradipine (DynaCirc), Nicardipine (Cardene), Nifedipine (Procardia/Adalat), Nisoldipine (Sular) • MOA: ↓ HR, ↓ Contractility, vasodilation • inhibits influx Ca+ into cardiac and vascular smooth muscle cells

8. Calcium Channel Blockers (CCB) • Side Effects: • ↓ HR, ↓BP, edema, angioedema, gingival hyperplasia, HA, flushing, dizziness • Constipation (verapamil), CHF exacerbation (verapamil/diltiazem), drug interactions (verapamil/diltiazem)

9. Digoxin (Lanoxin) • MOA: • Increases force of heart contractions, ↓ HR • Side Effects: • Manifestations of Toxicity: • Anorexia, N/V/D, visual changes, arrhythmias (PVCs), bradycardia • Increased Risk of Toxicity: • Renal impairment, low K+/Mg+, elderly, hypothyroid; Drug interactions

10. Diuretics • Examples: • Loop— • Furosemide (Lasix), Bumetanide (Bumex), Torsemide (Demedex), Ethacryinic Acid • Thiazide— • Hydrochlorothiazide (HCTZ), Chlorthiazide (Diuril), Chlorthalidone, Metolazone (Zaroxolyn) • Potassium Sparing— • Amiloride, Triamterene; • Aldosterone Antagonists— • Spironolatone (Aldactone), Eplerenone (Inspra) • MOA: eliminates extracellular fluid • Loop: inhibits Cl- reabsorption in loop of Henle • Thiazide: inhibits reabsorption of Na+ and water, vasodilation • Potassium Sparing: inhibits K+ channels • Aldosterone Antagonists: block aldosterone

11. Diuretics—Side Effects • Loop: • ↓K+, ↓Na+, ↓Ca+, ↓Mg+; Ototoxicity, Photosensitivity, Dehydration • Thiazide: • ↓K+, ↓Na+, ↓Mg+; Hyperglycemia, ↑ Lipids, ↑Ca+, dehydration • Triamterene/Amiloride: • ↑ K+, GI upset, photosensitivity • Spironolactone, etc.: • ↑ K+, Gynecomastia, drowsiness, GI upset

12. Direct Vasodilators • Examples: Hydralazine, Minoxidil • MOA: • Relaxation smooth muscle, lowering pressure needed to push blood through vessels • Side Effects: • Hydralazine: • Headache, drug fever, peripheral neuropathy, hepatitis, skin reactions • Minoxidil: • Hair growth, fluid overload, use with BB to prevent reflex tachycardia

13. Nitrates • Examples: • Nitroglycerin, Isosorbide Mononitrate (ISMO, Monoket, Imdur), Isosorbide Dinitrate (Isordil) • MOA: • Relaxation of smooth muscle, lowering pressure needed to push blood through vessels • Side Effects: • Headache, flushing, hypotension, syncope, cyanosis (blue) may indicate methemiglobinemia

14. Anti-Adrenergic Agents • Examples • Alpha-1 Receptor Blocker—Doxazosin, Prazosin, Terazosin • Centrally Acting Agents—Clonidine, Methyldopa, Guanabenz, Guanfacine • MOA • Alpha-1 Receptor Blocker • Peripheral relaxation of smooth muscle causing vasodilation • Centrally Acting Agents • Stimulates alpha-2 adrenergic receptors in brain causing a peripheral reduction in sympathetic tone—↓ HR, ↓CO, ↓ peripheral resistance • Side Effects • Dizziness, drowsiness, syncope/hypotension, depression, dry mouth, rebound HTN

15. Anti-Thrombotics—Antiplatelets • Examples • Aspirin, Clopidrogel (Plavix), Prasugrel (Effient), Dipyridimole, Ticlodipine (Ticlid) • MOA • Inhibits platelet aggregation and clot formation • Side Effects • Bleeding • GI upset, thrombocytopenia

16. Anti-Thrombotics— Heparins, LMWH & Warfarin • Heparin, Enoxaparin (Lovenox), Dalteparin (Fragmin) • MOA—disruption of clotting cascade (antithrombin III) • Side Effects—bleeding, thrombocytopenia • Warfain (Coumadin) • MOA—disruption of vitamin K dependent clotting factors • Side Effects—bleeding, skin necrosis

17. Anti-Hyperlipidemic Agents • Statins (Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin) • MOA: blocks cholesterol synthesis and increases catabolism • Side Effects: HA, GI upset, elev LFT’s, myopathy, rhabdomyolysis; • **New FDA Warning not to exceed 40mg/day Simvastatin unless previously stable on dose without side effects. Do not increase patients beyond 40mg. • Fibric Acid Analogs (Gemfibrozil, Fenofibrate) • MOA: Decreases VLDL synthesis; increases VLDL/Triglyceride removal • Side Effects: elev LFT’s, myopathy, GI upset, diarrhea, cholelithiasis, rash/itching

18. Anti-Hyperlipidemic Agents • Cholesterol Absorption Inhibitor (Ezetimibe) • Side Effects: headache, angioedema • Omega 3 Fatty Acids (Lovaza) • Side Effects: halitosis, GI upset, weight gain, prolonged bleeding time • Niacin • Side Effects: flushing, itching, GI upset, hyperglycemia, elev LFT’s, elevated uric acid, myopathy w/ high dose statins/fibrates • Bile Acid Sequestrants • Side Effects: GI upset, bloating, constipation, drug interactions (decreases absorption)

19. Anti-Arrhythmic Agents • Class Ia Anti-Arrhythmic Agents • Depresses pacemaker rate, conduction and excitability • Quinidine • Side Effects: syncope, TdP, ↓ BP, n/v/d, HA, dizziness, tinitis, fever, thrombocytopenia • Procainamide • Side Effects: hypotension, TdP, SLE, n/v/d, fever, rash, hepatitis, agranulocytosis, HA, mood changes

20. Anti-Arrhythmic Agents • Class Ib—Lidocaine • Depresses abnormal cardiac activity, shortens action potential duration, prolongs diastole (extending time for recovery) • Side Effects: Hypotension, parasthesias, nausea, tremor, syncope, hearing disturbances, slurred speech, seizures • Class Ic—Propafenone • Similar to Quinidine, weak BB • Side Effects: metalic taste, proarrhythmias • Class II—Beta-Blockers

21. Anti-Arrhythmic Agents • Class III • Amiodarone • Broad spectrum of activity: lengthens action potential, weak CCB, non-competitive BB, alpha-receptor blocker • Effects: vasodilatation, bradycardia, heart block, TdP, pulmonary fibrosis, corneal deposits, visual disturbances, sun sensitivity, skin discoloration, constipation, hepatic dysfunction, ataxia, HA, tremor, drug interactions

22. Anti-Arrhythmic Agents • Class III, cont. • Dronedarone • Similar to amiodarone • Effects: bradycardia, TdP, GI upset, weakness, rash, liver injury, hepatic failure; new agent • Sotolol • Non-selective BB, prolongs action potential • Side Effects: fatigue, bradycardia, dizziness, dyspnea, proarrhythmias • Class IV—CCBs (Verapamil/Diltiazem)

23. Drug Interactions • Drugs affecting Absorption • Antibiotics alter GI Flora, affecting Warfarin • Drugs affecting Protein Binding • Drugs affecting Metabolism • Increases Metabolism of Medication • Rifampin ↑ warfarin metabolism, decreasing INR • Decreases Metabolism of Medication • Amiodarone inhibits hepatic enzymes from metabolizing key medications • Drugs affecting Excretion • Amiodarone decreases digoxin clearance

24. Drug Interactions to Consider • Cialis/Viagra/Levitra potentiate Nitrates/Vasodilators = Hypotension! • Important to know if patients are taking these medications

25. Warfarin Interactions • Warfarin—Everything! • “the biggies” • Amiodarone • Sulfamethoxazole (Septra/Bactrim) • Metronidazole (Flagyl) • Quinolones(Cipro, etc) • Rifampin

26. Warfarin Interactions

27. Drug Interactions to Consider • NSAIDs & ACE-I • Can reduce the antihypertensive effect of ACE-I or cause/worsen renal failure • Digoxin & Amiodarone • May need less digoxin if on chronic amiodarone • Drugs prolonging QT interval • Can cause arrhythmia when combined with other drugs prolonging QT interval

28. QT Prolongation • Anti-arrhythmic medications known to prolong QT Interval • Amiodarone • Dofetilide • Procainamide • Quinidine • Other medications with potential to prolong QT Interval • Droperidol • Erythromycin • Clarithromycin • Haloperidol • Methadone • Ziprasidone • Many others…

29. Questions • ????