Drugs Affecting the Cardiovascular System Felix Hernandez, M.D.

Diuretics Thiazide Diuretics Chlorothiazide MOA: inhibits sodium and chloride reabsorption in the distal tubule Indication: is the ideal starting agent for HTN. Is also used to treat chronic edema and hypercalcuria Side Effects: hypokalemia, hyponatremia, hyperglycemia, Contraindications: pregnancy, anuria

Diuretics Loop Diuretics Furosemide (Lasix) MOA: inhibits chloride reabsorption in the thick ascending loop. Causes high losses of potassium in the urine. Indications: preferred diuretic for patients with a low GFR and in hypertensive emergencies. Is also used for edema and to lower serum potassium levels Side Effects: hyponatremia, hypokalemia, hypocalcemia, dehydration, hypotension, ototoxicity Contraindications: anuria and electrolyte depletion

Diuretics Potassium Sparing Diuretics Amiloride MOA: directly increases sodium excretion and decreases potassium secretion in the DCT Indications: used in conjunction with other diuretics to treat HTN Side Effects: Hyperkalemia, glucose intolerance in DM patients Has a more rapid onset than Spironolactone Spironolactone (Aldactone) MOA: Antagonist of Aldosterone Indications: Used with thiazides for edema related to CHF, cirrhosis and nephrotic syndrome. Also used to diagnose and treat hyperaldosteronism Side Effects: Same as Amiloride plus endocrine imbalances (hirsutism, oily skin, acne)

Diuretics Osmotic Diuretics Mannitol MOA: osmotically inhibits sodium and water reabsorption Indications: ARF, brain edema, removing OD of some drugs Side Effects: headache, dizziness, polydipsia, confusion, chest pain

Presynaptic Adrenergic Blockers Clonidine  alpha 2 Methyldopa  methylnorepinephrine

Peripheral Anti-adrenergics Reserpine MOA: partially depletes catecholamine stores in the PNS and CNS causing a decrease in TPR, HR and CO Indications: seldom used for mild to moderate HTN Side Effects: parasympathetic predominance Contraindications: CHF, asthma, bronchitis, PUD, depression. All related to the parasympathetic predominance

Alpha and Beta Blockers Alpha-1 Blockers Prazosin Doxazosin (Cardura) Mixed alpha and beta blockers Labetolol Carvedilol (Coreg) Can cause further suppression of a failing heart Beta Blockers Atenolol Preferentially blocks Beta-1 receptors Metoprolol (Lopressor) Timolol

Vasodilators ACE Inhibitors MOA: Inhibit angiotensin converting enzyme in the lung which reduces the production of angiotensin II a vasoconstrictor. Also suppresses aldosterone. Indications: HTN, DOC for HTN with DM, CHF, MI for reperfusion Side Effects: first dose hypotension, dizziness, dry hacking cough Contraindications: pregnancy, bilateral renal artery stenosis Drugs: Captopril Lisinopril Enalapril

Vasodilators Angiotensin Receptor Blockers (ARB) MOA: antagonist at angiotensin II receptor Indications: HTN Side Effects: hypotension and dizziness Contraindications: pregnancy Drugs: Losartan (Cozaar) Valsartan (Diovan)

Direct Vasodilators Hydralazine MOA: relaxes arterioles (not veins) independent of sympathetic interactions. Causes a decrease in BP with a reflex tachycardia, increased CO and increased renal blood flow Indications: moderate HTN, can be used in pregnant women with HTN Side Effects: reflex tachycardia, fluid retention, Lupus like syndrome, peripheral neuritis with long term treatment due to vit. B6 Contraindications: patients with ischemic heart disease

Direct Vasodilators Nitroprusside MOA: is converted to nitric oxide which induces cGMP which then relaxes smooth muscles by dephosphorylating myosin Indications: Hypertensive crisis Side Effects: severe hypotension, cyanide toxicity and hepatotoxicity Contraindications: none

Calcium Chanel Blockers Verapamil (Isopten) MOA: blocks calcium influx causing dilation of peripheral arterioles and reducing afterload. Indications: DOC for acute paroxysmal supraventricular tachycardia, DOC to slow ventricular response in A-fib Side Effects: constipation, hypotension, bradycardia, edema, dizziness Contraindications: patients on IV Beta blockers or Digitalis, A-V node blocks, heart failure, hypotension

Calcium Chanel Blockers Diltiazem (Cardizem) MOA: dilates peripheral arterioles leading to a decreased afterload, increases oxygen supply to the myocardium by preventing sympathetic-induced coronary artery spasm. Indications: reduction of angina episodes, increased exercise tolerance in stable angina, HTN Side Effects: edema, headache, rash Contraindications: AV node block, SSS, hypotension, pulmonary congestion

Calcium Chanel Blockers Nifedipine (Procardia) MOA: more potent peripheral vasodilation, doesn’t dilate coronary arteries, causes a reflex in crease in HR and CO Indications: no longer used as a single agent due to toxicity Side Effects: MI, peripheral edema, pulmonary edema, transient hypotension, reflex tachycardia Contraindications: hypotension

Anti-anginal Agents Nitrates Nitroglycerin Isosorbide Dinitrate MOA: dilates large myocardial arteries to increase blood flow to the heart. Reduces cardiac preload by reducing venous tone which allows pooling of blood in the periphery Indications: DOC for angina. Used immediately before exercise or stress to prevent ischemic episodes Side Effects: hypotension with rebound tachycardia, cerebral ischemia, contact dermatitis with transdermal, aggravation of peripheral edema Isosorbide Dinitrate Used for prophylaxis of angina not for acute attacks Has a faster onset of action sublingual than oral

Cardiac Glycosides Digoxin MOA: inhibits sodium/potassium ATPase and increases the inward current of calcium. This leads to an increased contraction, increased CO and decreased heart size, venous return and blood volume. Causes diuresis by increased renal perfusion. Slows ventricular rate in A-fib by increased sensitivity of AV nodes to vagal inhibition. Increases peripheral resistance Indications: heart failure, A-fib, paroxysmal tachycardia Side Effects: bradycardia, nodal blocks, arrhythmias Contraindications: V-fib, severe bradyacrdia, allergic reactions to drug class

Drugs for Lipid Disorders Cholestyramine MOA: forms insoluble complexes with bile salts allowing them to be excreted in feces. The body compensates by increasing the number of LDL receptors and oxidizing cholesterol to bile acids Indications: LDL>190 or 160 with 2 risk factors Lipid Profile Effects: decreases TC, and LDL Increases Triglycerides, VLDL and HDL

Drugs for Lipid Disorders Niacin MOA: unclear, may reduce VLDL synthesis and secretion Indications: same as Cholestyramine Profile changes: Decreases TC, triglycerides, VLDL, and LDL Increases HDL

Drugs for Lipid Disorders Ezetimibe (Zetia) MOA: inhibits cholesterol absorption in the GI Indications: hypercholesterolemia Profile Changes: Decreases LDL and triglycerides Increases HDL

Statins MOA: inhibit HMG-CoA reductase in the liver which is the enzyme that catalyzes the rate limiting step in cholesterol synthesis. Indications: Same Profile Changes: Decreases TC, LDL, VLDL and Triglycerides Increases HDL Side Effects: Myalgia Drugs: Simvastatin (Zocor) Atorvastatin (Lipitor) Rosuvastatin (Crestor)

Anticoagulants Heparin MOA: binds to antithrombin III forming a complex which then binds to and inhibits activated clotting factors. Indications: DVT and PE prophylaxis post-op, maintaining extracorporeal circulation with open heart surgery and dialysis, and achieving immediate anticoagulation Side Effects: bleeding, hemorrhage, thrombocytopenia, necrosis at injection site Notes: Protamine Sulfate inactivates it and can be used as an antagonist if severe bleeding occurs. Monitor PTT

Anticoagulants Warfarin MOA: antagonizes vitamin K and inhibits the synthesis of vitamin K dependent clotting factors (II, VII, IX, and X) Indications: DVT, IHD, PE, artificial heart valves, A-fib Side Effects: bleeding, hemorrhage, necrosis Notes: Monitor PT

Antiplatelet Agents Aspirin/Ibuprofen Clopidogrel (Plavix) MOA: inhibits cyclooxygenase thus blocking platelet aggregation Indications: to reduce the risk of recurrent TIA or stroke, reduce risk of MI in patients with unstable angina or prior infarction Side Effects: GI ulceration, bleeding hemorrhage Clopidogrel (Plavix) MOA: blocks platelet aggregation by inhibiting ADP receptor Indications: reduction of atherosclerotic events Side Effects: neutropenia and same as aspirin

Thrombolytic Agents Streptokinase MOA: activates plasminogen to plasmin. Plasmin digests fribrin and fibrinogen into degradation products which also cause anticoagulation by inhibiting the formation of fibrin. Indications: to lyse thrombi in ischemic coronary arteries after infarction. PE, DVT, occluded cannula Side Effects: bleeding, bruising, rare but can have an anaphylactic response (strep toxin)

Thrombolytic Agents Tissue Plasminogen Activator (TPA) MOA: binds to fibrin, then activates fibrin-bound plasminogen to plasmin Indications: to reperfuse coronary arteries that are occluded Side Effects: hematoma at catheterization site Alteplase/Reteplase MOA: recombinant form of TPA Indications: Acute MI, Ischemic stroke, PE Side Effects: Bleeding