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 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

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 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

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