Drugs Affecting the Cardiovascular System mashehabat@just.edu.jo

Drugs Affecting the following disorders CHF Disrythmias Angina Hypertension Hypercholestremia

Congestive Heart Failure The Problem: Heart cannot pump enough blood Causes: Htn, arteriosclerosis, valvular disease The Solution(s): Vasodilator Diuretics Inotropes } Goal is to increase cardiac output

Congestive Heart Failure The Problem: Heart cannot pump enough blood Causes: Htn, arteriosclerosis, valvular disease The Solution(s): Vasodilator Diuretics Inotropes } Goal is to increase cardiac output

Vasodilators How do they work? Mechanism 1: ACE converts Angiotensin I to Angiotensin II Angio II has effects as shown ACE inhibitors decrease A II End Results: Decrease fluid retention, afterload Examples: Enalapril, Captapril Angiotensin I ACE Angiotensin II ↑ Sympathetic Output ↑ Bradykinin Constrict Vascular Smooth Muscle ↑ Na+/H20 Retention

Other Vasodilators: Mechanism 2: Direct smooth muscle relaxants Nitrates Venous dilators Reduce preload Eg: sodium nitropruside Calcium channel blockers Amlodipine, felodipene

Diuretics Bottom line: they decrease fluid volumes Four Flavours: Carbonic anhydrase inhibitors Loop diuretics Thiazide diuretics K+-sparing

Diuretics: Sites of Action Carbonic Anhydrase Inhibitors Eg: Acetazolamide Thiazides Eg: Chlorothiazide Na+ Cl- HCO3- K+ - Sparing Eg: ? Na+ Na+ Cl- K+ K+ Loop Diuretics Eg: Furosemide

Inotropes Increase force of contraction All increase intracellular cardiac Ca++ concentration Eg: Digitalis (cardiac glycoside) Dobutamine (β-adrenergic agonist) Amrinone (PDE inhibitor)

How Digitalis Works Out Na+ Na+ ATP ADP + Pi Ca++ K+ Ca++ In Digitalis

Drugs for Treating Arrhythmias The Problem: Abnormal cardiac impulse formation/conduction Can be atrial, supraventricular, ventricular in origin The solution Several different classes of drugs All affect cardiac action potentials

Cardiac Action Potential Example of effects of Antiarrhythmics Quinidine (a Class I drug) Membrane Potential (mV) Sotalol (a Class III drug) Time (Seconds)

Actions of Antiarrhythmic Drugs Class of Drug Action I Na+ Channel Blocker II Β-Adrenoreceptor Blocker III K+ Channel Blocker IV Ca++ Channel Blocker

What is angina? What causes it? Antianginal Drugs What is angina? What causes it?

Angina Problem: Possible Solutions: Blood flow to myocardium is insufficient Causes: narrowed artery or arterial spasm Possible Solutions: Relax vascular smooth muscle Reduce work of the heart

Angina Drugs Organic nitrates Calcium Channel Blockers Β-Blockers Nitroglycerin Nitrate converted to nitric oxide Calcium Channel Blockers Diltiazem, Nifedipine Β-Blockers Propranolol Ca++ Nifedipine cGMP Propranolol Nitrate NO Pi Myosin Light Chain

Antihypertensive Drugs

What Determines Arterial Pressure? Heart Rate Filling Pressure ~ ~ Peripheral Resistance Arterial Pressure Cardiac Output X Contractility Arteriolar Radius

Antihypertensive Drugs The Problem: Sustained diastolic pressure can lead to CHF, infarction, end-organ damage Possible Solutions: Mild Htn can be treated with a single drug Severe Htn treated with several drugs, choice of which depends on patient needs

Some Examples of Antihypertensive Drugs Beta Blockers Atenolol, Metoprolol More selective than propranolol for β1 receptors Diuretics Hydrochlorothiazide, spironolactone ACE Inhibitors Captopril Calcium Channel Blockers Nifedipine, etc Centrally-Acting Drugs Clonidine Vasodilators Hydralazine

Hypertensive Crisis BP = 210/150 Drugs that may be used: Sodium Nitroprusside Dilates arterial and venous smooth muscle Diazoxide vasodilator Labetolol - and β-blocker Drug of choice

Lipid-Lowering Drugs The Problem: Solutions: High serum levels of cholesterol- and/or triacylglycerol molecules Solutions: Decrease lipoprotein synthesis Increase lipoprotein catabolism Increase cholesterol removal

How They Work Niacin: Simvastatin Colestipol Fatty Acid Liver Cell Inhibits lipolysis in fat cells Simvastatin Inhibits liver enzymes Colestipol Binds to bile salts Enzyme Lipid

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