Drugs Affectingcardiovascular System1

7/31/2019 Drugs Affectingcardiovascular System1

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Drugs Affecting

the Cardiovascular System

[email protected]


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Drugs Affecting the following disorders

CHF

Disrythmias

Angina Hypertension

Hypercholestremia


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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


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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


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Vasodilators

How do they work?

Mechanism 1:

ACE converts Angiotensin I toAngiotensin II

Angio II has effects as shown

ACE inhibitors decrease A II

End Results:

Decrease fluid retention,afterload

Examples:

Enalapril, Captapril

Angiotensin I

Angiotensin II

ACE

Sympathetic

Output

Constrict

Vascular Smooth

Muscle Na+/H20

Retention

Bradykinin


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Other Vasodilators:

Mechanism 2:

Direct smooth muscle relaxants

Nitrates

Venous dilators

Reduce preload

Eg: sodium nitroprusideCalcium channel blockers

Amlodipine, felodipene


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Diuretics

Bottom line: they decrease fluid volumes

Four Flavours:

Carbonic anhydrase inhibitors

Loop diuretics

Thiazide diuretics

K+-sparing


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Diuretics:Sites of Action

Na+

Cl-

K+

Na+

Cl-HCO3

-

Na+

K+

Carbonic AnhydraseInhibitors

Eg: Acetazolamide

Loop DiureticsEg: Furosemide

ThiazidesEg: Chlorothiazide

K+ - SparingEg: ?


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Inotropes

Increase force of contraction

All increase intracellular cardiac Ca++

concentration

Eg:

Digitalis (cardiac glycoside)

Dobutamine (-adrenergic agonist)

Amrinone (PDE inhibitor)


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How Digitalis Works

Ca++Ca++

Na+

K+ATP ADP + Pi

Out

In

Digitalis

Na+


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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


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Cardiac Action PotentialExample of effects of Antiarrhythmics

M

embranePotential

(mV)

Time (Seconds)

Quinidine (a Class I drug)

Sotalol (a Class III drug)


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Actions of Antiarrhythmic Drugs

Class of

Drug

Action

I Na+ Channel Blocker

II -Adrenoreceptor Blocker

III K+ Channel Blocker

IV Ca++ Channel Blocker


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Antianginal Drugs

What is angina?

What causes it?


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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


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Angina Drugs Organic nitrates

Nitroglycerin

Nitrate converted to nitric oxide

Calcium Channel Blockers

Diltiazem, Nifedipine

-Blockers

Propranolol

Nitrate NO

cGMP

Myosin Light Chain

Pi

Ca++

Nifedipine

Propranolol


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Antihypertensive Drugs


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What Determines Arterial Pressure?

Arterial Pressure Cardiac OutputPeripheral

Resistance~~ X

ArteriolarRadius

Heart

Rate

Contractility

Filling

Pressure


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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


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Some Examples of


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


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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


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Lipid-Lowering Drugs

The Problem:

High serum levels of cholesterol- and/or

triacylglycerol molecules

Solutions:

Decrease lipoprotein synthesis

Increase lipoprotein catabolismIncrease cholesterol removal


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How They Work

Niacin:

Inhibits lipolysis in fat cells

Simvastatin Inhibits liver enzymes

Colestipol

Binds to bile salts

Fatty Acid

Liver

Cell

Enzyme

Lipid


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See you on Saturday

11-12am

THANK YOU

Drugs Affectingcardiovascular System1

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