Drugs Affecting the Cardiovascular System

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Drugs Affectingthe Cardiovascular System

• Pharmacology 49.222
• Bill Diehl-Jones RN, PhD
• Faculty of Nursing and Department of Zoology

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Agenda

• Zen Review
• Drugs Affecting the following disorders
• CHF
• Disrythmias
• Angina
• Hypertension
• Hypercholestremia
• Clinical Gems

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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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VasodilatorsHow 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
? Sympathetic Output
? Bradykinin
Constrict Vascular Smooth Muscle
? Na/H20 Retention
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Other Vasodilators

• Mechanism 2
• Direct smooth muscle relaxants
• Nitrates
• Venous dilators
• Reduce preload
• Eg sodium nitropruside
• Calcium 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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DiureticsSites of Action
Carbonic Anhydrase Inhibitors Eg Acetazolamide
Thiazides Eg Chlorothiazide
Na Cl-
HCO3-
K - Sparing Eg ?
Na
K
Loop Diuretics Eg Furosemide
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Inotropes

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

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How Digitalis Works
Out
Na
Na
ATP
ADP Pi
Ca
K
Ca
In
Digitalis
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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
Quinidine (a Class I drug)
Membrane Potential (mV)
Sotalol (a Class III drug)
Time (Seconds)
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Actions of Antiarrhythmic Drugs
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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

Ca
Nifedipine
Propranolol
cGMP
Nitrate
NO
Pi
Myosin Light Chain
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Antihypertensive Drugs
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What Determines Arterial Pressure?

Peripheral Resistance

Arterial Pressure
Cardiac Output
X
Arteriolar Radius
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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

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Some Examples of Antihypertensive Drugs

• Beta Blockers
• Atenolol, Metoprolol
• More selective than propranolol for ß1 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 ß-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 catabolism
• Increase cholesterol removal

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How They Work
Fatty Acid
Liver Cell

• Niacin
• Inhibits lipolysis in fat cells
• Simvastatin
• Inhibits liver enzymes
• Colestipol
• Binds to bile salts

Enzyme
Lipid
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Clinical Gems