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

3.  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.  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.  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—b locking of catecholemines › Non-Selective BB blocks both beta1 receptors (heart) and beta2 receptors (bronchial and vasculature sites)

6.  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.  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.  Side Effects: › ↓ HR, ↓BP, edema, angioedema, gingival hyperplasia, HA, flushing, dizziness › Constipation (verapamil), CHF exacerbation (verapamil/diltiazem), drug interactions (verapamil/diltiazem)

9.  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. 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.  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.  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.  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.  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.  Examples › Aspirin, Clopidrogel (Plavix), Prasugrel (Effient), Dipyridimole, Ticlodipine (Ticlid)  MOA › Inhibits platelet aggregation and clot formation  Side Effects › Bleeding › GI upset, thrombocytopenia

16.  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.  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.  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.  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.  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.  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. 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. › 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.  Cialis/Viagra/Levitra potentiate Nitrates/Vasodilators = Hypotension! › Important to know if patients are taking these medications

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

26. MedicationsEffect on PT/INRMechanism Estrogens, Vitamin K↓Increased synthesis of clotting factors Methimazole, Propylthiouracil↓ Reduced catabolism of clotting factors Barbituates, carbamazepine, chronic ETOH, dicloxacillin, nafcillin, rifampin, phenytoin↓Increased warfarin metabolism cholestyramine, colestipol, sucralfate↓Reduced warfarin absorption azathioprine, cyclophosphamide, cyclosporine, mesalamine↓Unexplained thyroid hormones↑ Increased catabolism of clotting factors cetotetan, vitamin E↑ Decreased synthesis of clotting factors Broad spectrum antibiotics↑ Impaired Vitamin K production by GI flora acute ETOH, allopurinol, amiodarone, azithromycin, ciprofloxacin, erythromycin, clarithromycin, fluconazole, fluorouracil, fluoxetine, ketoconazole, metronidazole, omeprazole, phenytoin, sulfamethoxazole, propafenone↑Decreased warfarin metabolism acetaminophen, androgens, vitamin C, clofibrate, corticosteroids, gemfibrozil, statins↑Unexplained aspirin, clopidrogel, NSAIDs, SSRIs, ticlodipine0Increased bleeding risk

27.  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.  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.  ????