1. Drugs Acting on the Heart
Munir Gharaibeh
Faculty of Medicine
Second Semester, 2010/2011

2. Munir Gharaibeh MD, PhD, MHPE
Heart Failure
Definition.
Factors Affecting Cardiac Output:
Preload.
Afterload.
Heart rate.
Contractility of heart muscle.
April 19
Munir Gharaibeh MD, PhD, MHPE

3. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

4. Munir Gharaibeh MD, PhD, MHPE
Heart Failure
Causes of Heart Failure:
Ischemic heart disease.
Hypertension.
Cardiomyopathy.
Valvular heart disease.
Etc….
April 19
Munir Gharaibeh MD, PhD, MHPE

5. Munir Gharaibeh MD, PhD, MHPE
Heart Failure
Clinical Picture:
Sympathetic compensation:
a- Tachycardia.
b- Increased myocardial contractility.
c- Vasoconstriction leading to redistribution of blood to important viscera
d- Renin release leading to increased plasma volume
Decreased cardiac output
Congestion.
April 19
Munir Gharaibeh MD, PhD, MHPE

6. Compensatory Mechanisms in Heart Failure
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Munir Gharaibeh MD, PhD, MHPE

7. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

8. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

9. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

10. Drugs used in Heart Failure
Most of the drugs are used only to relieve the symptoms, they do not really cure the disease.
Diuretics.
Angiotensin converting enzyme inhibitors(ACEI).
Positive inotropic drugs.
Vasodilators.
ß blockers.
April 19
Munir Gharaibeh MD, PhD, MHPE

11. Munir Gharaibeh MD, PhD, MHPE
Diuretics
Work directly on the kidneys to increase salt and water excretion.
They only relieve edema; pulmonary, leg edema, and heart distension.
May cause dehydration and hypokalemia.
In high doses, might decrease cardiac output.
They stimulate renin-angiotensin- aldosterone system.
Will be discussed later.
April 19
Munir Gharaibeh MD, PhD, MHPE

12. Angiotensin Converting Enzyme Inhibitors(ACEI).
Also used in hypertension.
Reduce salt and water retention.
Cause dilation of arterioles, and consequently, reduce the afterload, leading to enhancement of cardiac output.
Only drugs which prolong the survival of patients.
Can cause hypotension and hyperkalemia.
April 19
Munir Gharaibeh MD, PhD, MHPE

13. Angiotensin Converting Enzyme Inhibitors "ACEI"
Captopril
Enalapril
Lisinolapril
Quinalapril
Fosinolapril
All are similarly effective
Might differ in toxicity
April 19
Munir Gharaibeh MD, PhD, MHPE

14. Angiotensin Converting Enzyme Inhibitors "ACEI"
Toxicity:
Hypotension
Renal Impairment proteinurea
K+ retention
Cough
April 19
Munir Gharaibeh MD, PhD, MHPE

15. Angiotensin (AT1) Receptor Blockers (ARBs)
Losartan.
Candesartan.
Valsartan.
Irbesartan.
Telmisartan.
Not superior to ACEIs, but may be useful for patients who can not tolerate ACEIs because of cough.
April 19
Munir Gharaibeh MD, PhD, MHPE

16. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

17. Positive Inotropic Agents
Cyclic AMP Independent Agents:
Digoxin
Cyclic AMP Dependant Agents:
-adrenergic Agonists
April 19
Munir Gharaibeh MD, PhD, MHPE

18. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

19. Munir Gharaibeh MD, PhD, MHPE
Digitalis Glycosides
History:
Prototype for inotropic agents.
Egyptians Squill
Chinese Toad skin
William Withering Foxglove 1785
April 19
Munir Gharaibeh MD, PhD, MHPE

20. Munir Gharaibeh MD, PhD, MHPE
Digitalis Glycosides
Mechanism:
Inhibition of Na+/K+ ATPase
April 19
Munir Gharaibeh MD, PhD, MHPE

21. Munir Gharaibeh MD, PhD, MHPE
April 19
Munir Gharaibeh MD, PhD, MHPE

22. Munir Gharaibeh MD, PhD, MHPE
Digitalis Glycosides
Actions:
Positive Inotropic
Stimulate the vagus nerve
Block AV conduction.
Enhance ventricular electrical activity.
April 19
Munir Gharaibeh MD, PhD, MHPE

23. Munir Gharaibeh MD, PhD, MHPE
Digitalis Glycosides
Pharmacokinetics:
Long half life.
Loading dose required.
Can accumulate.
Acceptable plasma levels: 1-2 meq/liter.
April 19
Munir Gharaibeh MD, PhD, MHPE

24. Munir Gharaibeh MD, PhD, MHPE
Digitalis Glycosides
Toxicity:
G.I.T.
Visual.
Neurologic.
Cardiac: bradycardia, heart block, ventricular extrasystoles.
Interactions.
Treatment of Toxicity:
Stop the dug or reduce the dose.
Ensure adequate K+ level.
Cardiac pacemeker.
Digitalis antibodies( Digoxin Immune Fab)
April 19
Munir Gharaibeh MD, PhD, MHPE

25. Munir Gharaibeh MD, PhD, MHPE
Digitalis Glycosides
Therapeutic Benefits:
Nowadays, only indicated in CCHF associated with supraventricular arrhythmia.
Decreases morbidity.
Does not reduce mortality.
April 19
Munir Gharaibeh MD, PhD, MHPE

26. Positive Inotropic Agents
Cyclic AMP Dependent Agents:
-adrenergic Agonists:
All increase myocardial oxygen consumption, so not helpful for chronic use.
May be used (IV) for short term or in acute heart failure.
NE:
Was used in cardiogenic shock, but caused severe vasospasm and gangrene .
EP:
Still used in cardiac arrest, by intracardiac injection.
April 19
Munir Gharaibeh MD, PhD, MHPE

27. Positive Inotropic Agents
Dopamine:
Widely used in cardiogenic shock.
Low doses: stimulates DA1 receptors leading to renal vasodilation and improved renal function.
Intermediate doses: works on β1 receptors leading to positive inotropic actions.
High doses: stimulates α receptors leading to vasoconstriction and elevation of blood pressure.
Can cause arrhythmias and ischemic changes.
Dobutamine:
Selective β1 agonist, used intermittently (IV) in CCHF.
Has more inotropic than chronotropic actions.
April 19
Munir Gharaibeh MD, PhD, MHPE

28. Munir Gharaibeh MD, PhD, MHPE
Vasodilators
Affect preload and/or afterload without directly affecting contractility.
Consequently, can decrease myocardial ischemia, enhance coronary blood flow and decrease O2 consumption.
Can be used, only by expert hands, in acute heart failure and for short periods in CCHF.
Can be combined with ACEI, Diuretics and digitalis.
April 19
Munir Gharaibeh MD, PhD, MHPE