negative ionotropic drugs - used in congestive heart failure

1. CONGESTIVE HEART
FAILURE
Introduction
 Condition where the heart is unable to provide
enough perfusion to the peripheral organs to meet
metabolic demands
 Characterized by
1. Reduced cardiac output
2. Increased total peripheral resistance
Progressing to CHF, accompanied by peripheral and
pulmonary edema

2. Therapeutic overview of CHF
1. Reduced force of contraction
2. Decreased cardiac output
3. Increased total peripheral resistance
4. Development of edema
5. Decreased exercise tolerance
6. Ischemic heart disease
7. Ventricular remodeling, decreased function
8. Sudden death

3. GOALS
Alleviation of symptoms and improving the quality of life
Arrest ventricular remodeling
Prevent sudden death
NON DRUG THERAPY
Reduced cardiac work
Rest, weight loss
Low sodium diet

4. DRUG THERAPY
1. RENIN ANGIOTENSIN SYSTEM BLOCKERS
 ACE – INHIBITORS
 ANGIOTENSIN RECEPTOR BLOCKERS
2. DIURETICS
3. VASODILATORS
4. BETA- BLOCKERS
5. INOTROPIC DRUGS

5. DRUGS WITHOUT POSITIVE INOTROPIC EFFECT USED IN CHF
1. Diuretics : Furosemide, Spironolactone,
Eplerenone
2. Drugs acting on RAS :
 Angiotensin Receptor Blockers:
Losartan, Telmisartan
 ACE- Inhibitors: Captopril, Enalapril
3. Vasodilators: Hydralazine+Isosorbide
dinitrate, Nesiritide
4. Beta blockers : Carvedilol, Metoprolol,
Bisoprolol

6. DIURETICS
Mostly used drugs in heart failure management
Do not have direct effect on cardiac contractility
Acts mainly by
 Reducing venous pressure hence reducing ventricular
preload
Result:
Decreases salt and water retention.
Decreases edema and its symptoms
Reduction in cardiac size therefore improving pump efficiency

7. Furosemide ( Loop diuretic )
Used in symptomatic treatment of CHF
↓preload, ↓circulatory volume, improves pump efficacy
Removes peripheral edema, pulmonary congestion
MOA: Inhibit the cotransport of Na+/K+/2Cl-
Net loss of water and sodium
S/E: Hypokalemia, Ototoxicity, Hyperuricaemia,
Hyperlipidemia
Contraindication : Renal insufficiency, Pregnancy

8. Hydrochlorthiazide ( Thiazide diuretic )
Used less frequently in CHF, these are used in special
cases where resistance developed to loop diuretics
after chronic use
In such a situation, Hydrochlorthiazide may be added
with loop diuretics
MOA: inhibits Na+/Cl- cotransporter
S/E: Hypokalemia, Hypotension, Hyponatremia,
Hypercalcemia

9. Spironolactone
Aldosterone antagonist diuretics
Spiranolactone enhances diuresis by promoting sodium
and water excretion (while retaining potassium)
Added benefits like: decreases mortality & morbidity in
patients with severe CHF who are receiving ACE-I and
other drugs
Prevents myocardial as well as vascular fibrosis which is
responsible for pathological remodelling of heart
S/E: Major side effect is Hyperkalemia

10. RENIN ANGIOTENSIN SYSTEM

11. ACE-Inhibitors ( CAPTOPRIL)
Drugs of choice in CHF
Act by blocking ACE, which converts Angiotensin I to potent
Angiotensin II , as a result
1. Vasodilatation ( ↓Vascular resistance )
2. Decreased Aldosterone release leading to decreased salt and
water retention
3. Decreased Norepinephrine release , decreased Cardiac
remodelling
S/E: Hyperkalemia, Hypotension , Cough
Contraindication: Pregnancy, Renal artery stenosis,
Angioedema .

12. ARB’s ( LOSARTAN)
Considered in patients who are intolerant to ACE-I
Potent competitive antagonists of AT1 Receptor
The result is
1. Vasodilatation
2. Decreases Sympathetic activity
3. Decreased Aldosterone release
4. Decreased renal sodium reabsorption
S/E: Hyperkalemia, Renal failure, Hypotension
Contraindications: Pregnancy, Renal artery stenosis,
Hyperkalemia

13. Advantages
Improves symptoms
Improves exercise tolerance
Slows progression of disease
Prolonged survival in established cases

14. VASODILATORS
Effective in acute heart failure
Reduces preload( venodilatation)
Reduced afterload ( arteriolar dilatation)
Isosorbide dinitrate and Hydralazine reduce
remodeling

15. BRAIN NATRIURETIC PEPTIDE(BNP)
Nesiritide – synthetic BNP
Used in acute decompensated heart failure
Increases cGMP in the smooth muscle of Arteries and
Veins, hence decreasing their tone
It also causes diuresis
Adverse effect: Excessive Hypotension, Renal damage

16. BETA BLOCKERS
As a general rule, beta-blockers are contraindicated in
CHF
All beta-blockers are not beneficial in CHF
Bisoprolol, Carvedilol, Metoprolol are preferred, as these
drugs improve ventricular function and prolong survival
in these patients
The suggested mechanism for the favorable effects of the
above 3 drugs
1. Reduction in cardiac remodeling
2. Blunting of the adverse effects of higher circulating
levels of catecholamines ( including apoptosis)
3. Decreases heart rate

17. Thank you