Mwilu Daniel Muthusi

PHAM/MG/1991/09/19

DRUGS USED IN HEART FAILURE

Heart failure occurs when cardiac output is inadequate to provide required oxygen by the body oftenly
punctuated with cases of acute decompensation that requires hospitalisation in many cases.

Treatment is therefore is based on these main goals:(1) Reduction of symptoms and slowing progression
as much as possible during relatively stable periods and (2) managing acute episodes of decompesated
failure.

Below is a listing of drug groups used in heart failure.

1. Diuretics
2. Aldosterone receptor blockers
3. Angiotensin converting enzyme inhibitors
4. Beta blockers
5. Cardiac glycosides
6. Vasodilators
7. Beta agonists
8. Bipyridines
9. Natriuretic peptides

Diuretics

The main action mechanism of these drug class in heart failure is through reduction of venous pressure
and ventricular preload.

Loop diuretics eg furosemide,torsemide,bumetanide work by causing reduced NaCl and KCl

reabsorption in thick ascending loop of henle in the nephron.

The effects of these action causes increased salt and water excretion,reduced cardiac preload and
afterload and reduction in pulmonary and peripheral edema .

Thus,these drugs can be used in acute and chronic heart failure patients.

It also aids in treatment of severe hypertension and edematous conditions.

Side effects of loop diuretics

 1. Hypovolemia
2. Hypokalemia
3. Orthostatic hypotension
4. Ototoxicity
5. Sulfonamide allergies
6.

Contraindications of loop diuretics

1. Furosemide, torsemide, bumetanide are contraindicated in patients who are susceptible to

allergic cross reactivity due to sensitivity to sulfonamides though it may be very rare.

Drug-drug interactions

✓NSAIDS eg Indomethacin cause a reduction in furosemide -induced diuretic effects by blocking

formation of vasodilator prostaglandins in the kidney and this increases total peripheral resistance.

Dosage

Furosemide -20mg

Torsemide - 10mg

Bumetanide - 0.5 mg

Ethacrynic acid ~ 50mg

Thiazide diuretics egs Hydrochlorothiazide,

✓They work by reducing NaCl reabsorption in the distal convoluted tubule.

✓Hence, they have similar effects as seen in loop diuretics though less efficacious

✓Clinically, they have been utilised for mild chronic heart failure.

✓other clinical utilisations include hypercalciuria treatment and mild - moderate hypertension.

Side effects of thiazide diuretics

1.Hyponatremia

2.Hypokalemia
3.Hyperglycemia

4.Hyperuricemia

5.Hyperlipidemia

6.Sulfonamide allergy

Aldosterone antagonists eg spironolacton,Eplerenone

These work by causing blocking aldosterone receptors in the collecting tubules of nephron thus leading
to increased salt and water excretion and a reduction in cardiac remodeling.

Clinical application

✓Chronic heart failure

✓aldosteronism

✓Hypertension

Side effects

1. Hyperkalemia
2. Spirinolactone exhibits gynecomastia

Angiotensin converting Enzyme Inhibitors

✓Include Captopril,enalapril.
✓ They inhibit Angiotensin converting enzyme thus rducind all formation by inhibiting
conversion of angiotensin 1 to angiotensin 11
The net effect is arteriolar and venous dilation, reduction of aldosterone secretion and reduction
in cardiac remodeling.
Clinical application
✓ Chronic heart failure
✓Hypertension
✓Diabetic renal disease
Side effects include:
✓cough
✓hyperkalemia
✓angioneurotic edema

Angiotensin Receptor blockers eg losartan,candesartan,telmisartan

✓antagonises all effects at AT 1 receptors and produces similar effects as those mentioned in
ACEIs
 Clinical application
✓chronic heart failure
✓The drugs in this class are used in patients intolerant to ACEI's
Side effects of ARB's
1. Hyperkalemia
2. Angioneurotic edema

Beta blockers eg's Carvedilol,metoprolol,bisoprolol,nebivolol etc

These offer Beta 1 receptor blockade competitively thus lead to a reduction in heart rate and blood
pressure.

Clinical application

In chronic heart failure to slow progression and in moderate to severe heart failure.

Side effects

✓bradycardia

✓AV block

✓Acute cardiac decompensation

✓Bronchospasm

Cardiac glycoside -Digoxin

These act by causing Na+/K+ -ATPase resulting in reduction in Ca2+ stored in sarcoplasmic reticulum.
Thus these leads to increased cardiac contractility

However,they have cardiac parasympathomimetic effects like slowed heart rate and slowed Av
conduction.

Clinical applications

✓Chronic symptomatic heart failure

✓Rapid ventricular rate and atrial fibrillation

Toxicities of digoxin

1. Nausea and vomiting

2. Diarrhea
3. Cardiac arrhythmias

Interactions of Digoxin
  Area under the curve is increase by 16% by Eplerenone
 St Johns wort reduces digoxin levels
 Clarythromycin increases digoxin levels and may lead to digoxin toxicity.

Vasodilators

Venodilators eg Isosorbide dinitrate

 These,cause release of Nitric oxide activating guanyl cyclase thus promoting venodilation , and
reducing preload and ventricular stretch.

Clinical applications

 Acute and chronic heart failure

 Angina

Toxicities

1. Postural hypotension
2. Tachycardia
3. Headache

Arteriolar dilators eg hydralazine

Increases Nitric oxide synthesis in the endothelium;and its effects is a reduction in blood pressure and
afterload; besides increasing cardiac output.

Clinical application

Hydralazine reduces mortality rates of heart failure when used with organic nitrates.

Side effects

1. Tachycardia
2. Fluid like retention
3. Lupus like syndrome

Combined arteriolar and venodilators eg nitroprusside

These increase Nitric oxide synthesis causing a reduction in blood pressure and preload and after load.

Clinical applications

In acute cardiac decompensation in heart failure

Side effects

1. Hypotension
2. Thiocyanate and cyanide toxicities

Beta adrenoceptors

1.Dobutamine it is a beta selective agonist whose actions potentiate increase in cAMP.

It has a pharmacological effect of increasing cardiac contractility and output

Clinical application

✓Acute decompesated heart failure

✓Intermittent therapy in chronic heart failure

Side effects

1. Arrhythmias

Interactions

Additive effects when used with other vasodilators.

2.Dopamine

These activates dopamine receptors and at higher doses beta and alpha adrenoceptors.

Dopamine has the effects of increasing renal blood flow and at higher dose increasing cardiac force and
blood pressure.

Clinical applications

 Acute decompensated heart failure

Toxicities

Arrhythmias

Bipyridines eg Milrinone
The drug is a phosphodiesterase type3 inhibitor that causes a increase in cAMp levels by inhibiting its
break down.

It has a net effect of causing vasodilation thus reducing peripheral vascular resistance and also plays role
in increase in cardiac contractility.

Clinical applications

 Acute decompensated heart failure.

Toxicities

✓Arrhythmias

Interactions

Additive effects when used with arrhtymogenic agents.

Natriuretic peptide eg Nesiritide

These activates BNP receptors ,and increases cGMP .

Clinical applications

Acute decompensated failure

Toxicities

 Renal damage
 Hypotension

Other drugs

✓Levosimendan - for acute heart failure(approved in Europe)

References

1. K.G.,Betram,T.J.,Trevor, (2012), Basic and Clinical Pharmacology,13th Edition,Mc Graw Hill Education,
(pp 209-219).

2.J.B.,Morris,P.Sharma.,A.F.,Mir.,N.P.,Bennet, (2012), Clinical Pharmacology,12th Edition, ELSEVIER,

(pp443 - 449).