Cardiac Pharmacology Update

2011 Cardiac Issues Nursing Breakout Session

Lani Steltz, PharmD.Pharmacist

Yakima Regional Medical Center

Outline

Common Cardiac Medications by Class› Examples› Mechanism of Action (MOA)› Side Effects

Common Interactions Questions

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

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

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)

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

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

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)

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

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

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

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

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

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

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

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

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

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)

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

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

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

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)

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

Drug Interactions to Consider

Cialis/Viagra/Levitra potentiate Nitrates/Vasodilators = Hypotension!› Important to know if patients are taking

these medications

Warfarin Interactions

Warfarin—Everything!› “the biggies”

Amiodarone Sulfamethoxazole (Septra/Bactrim) Metronidazole (Flagyl) Quinolones (Cipro, etc) Rifampin

Warfarin InteractionsMedications Effect on PT/INR Mechanism

Estrogens, Vitamin K ↓ Increased synthesis of clotting factors

Methimazole, Propylthiouracil ↓ Reduced catabolism of clotting factorsBarbituates, carbamazepine, chronic ETOH, dicloxacillin, nafcillin, rifampin, phenytoin ↓ Increased warfarin metabolism

cholestyramine, colestipol, sucralfate ↓ Reduced warfarin absorptionazathioprine, 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, ticlodipine 0 Increased bleeding risk

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

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…

Questions

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