1. Drugs Affecting the Cardiovascular System

2. Drugs Affecting the following disorders
CHF
Disrythmias
Angina
Hypertension
Hypercholestremia

3. 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

4. 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

5. 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

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

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

8. 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

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

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

11. 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

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

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

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

15. 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

16. 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

17. Antihypertensive Drugs

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

19. 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

20. 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

21. 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

22. 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

23. 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

24. See you on Saturday 11-12am
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