Drugs Affecting the Cardiovascular System

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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

Angiotensin I

ACE

End Results:
Decrease fluid retention, afterload

Angiotensin II
Sympathetic Output Constrict Vascular Smooth Muscle Bradykinin Na+/H20 Retention

Examples:
Enalapril, Captapril

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
HCO3Na+ Cl-

Thiazides
Eg: Chlorothiazide

Na+ Na+ ClK+ K+

K+ - Sparing
Eg: ?

Loop Diuretics
Eg: Furosemide

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

How Digitalis Works

Out Na+ Na+

ATP

ADP + Pi

In

Ca++

Ca++

K+

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

Membrane Potential (mV)

Quinidine (a Class I drug)

Sotalol (a Class III drug)

Time (Seconds)

Actions of Antiarrhythmic Drugs

Class of Drug
I II III IV

Action
Na+ Channel Blocker -Adrenoreceptor Blocker K+ Channel Blocker Ca++ Channel Blocker

Antianginal Drugs
What is angina? What causes it?

Angina
Problem:
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
Nitroglycerin
Nitrate converted to nitric oxide

Calcium Channel Blockers

Diltiazem, Nifedipine

-Blockers
Propranolol

Ca++ Nifedipine cGMP Propranolol

Nitrate

NO Pi Myosin Light Chain

Antihypertensive Drugs

What Determines Arterial Pressure?

Heart Rate Filling Pressure

Arterial Pressure

~ ~

Cardiac Output

Peripheral Resistance
Arteriolar Radius

Contractility

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 1 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 -blocker Drug of choice

Lipid-Lowering Drugs
The Problem:
High serum levels of cholesterol- and/or triacylglycerol molecules

Solutions:
Decrease lipoprotein synthesis Increase lipoprotein catabolism Increase cholesterol removal

How They Work

Niacin:
Inhibits lipolysis in fat cells

Fatty Acid Liver Cell

Enzyme

Simvastatin
Inhibits liver enzymes Lipid

Colestipol
Binds to bile salts

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