Drugs Affecting the Cardiovascular System

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

2. 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

3. 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

4. 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)

5. 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

6. Presynaptic Adrenergic Blockers • Clonidine  alpha 2 • Methyldopa  methylnorepinephrine

7. 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

8. 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

9. 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

10. 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)

11. 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

12. 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

13. 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

14. 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

15. 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

16. Anti-anginal Agents • Nitrates • Nitroglycerin • 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

17. 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

18. 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

19. 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

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

21. 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)

22. 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

23. 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

24. Antiplatelet Agents • Aspirin/Ibuprofen • 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

25. 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)

26. 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