Drugs used in heart failure

Congestive cardiac failure (CCF) is the combined failure of both the left and right sides of the heart. The incidence of cardiac failure in the UK is between 1 and 5 per 1000 per year, and doubles for each decade of life after the age of 45. CCF occurs when the cardiac output does not meet the needs of the tissues. This is thought to be due to defective excitation–contraction coupling, with progressive systolic and diastolic ventricular dysfunction.

Cardiac glycosides

Prototypical cardiac glycosides are digoxin and digitoxin. The drugs in this class shift the Frank–Starling ventricular function curve to a more favourable position. Chemically, cardiac glycosides have an aglycone steroid nucleus (the pharmacophore) that causes positive inotropic. An unsaturated lactone ring is responsible for cardiotonic activity and by adding additional sugar moieties the potency and pharmacokinetic distribution can be modulated.

Route of administrations_ORAL

  • Indications: heart failure, supraventricular arrhythmias
  • Contraindications: Heart block, hypokalaemia associated with the use of diuretics (the lack of competition from potassium potentiates the effects of cardiac glycosides on the Na+/K+ ATPase pump).
  • Adverse effects: Arrhythmias, anorexia, nausea and vomiting, visual disturbances, abdominal pain and diarrhoea.

Therapeutic notes: The cardiac glycosides have a very narrow therapeutic window, and toxicity is therefore relatively common. If this occurs, the drug should be withdrawn and, if necessary, potassium supplements and antiarrhythmic drugs administered. For severe intoxication, antibodies specific tocardiac glycosides are available.

Phosphodiesterase inhibitors

Examples of phosphodiesterase (PDE) inhibitors include enoximone and milrinone. These have been developed as a result of the many adverse effects and problems associated with cardiac glycosides. There is no evidence that these improve the mortality rate.

Route of administration_intravenous

  • Indications: PDE inhibitors are given for severe acute heart failure that is resistant to other drugs.
  • Adverse effects: Nausea and vomiting, arrhythmias, liver dysfunction, abdominal pain, hypersensitivity.

Beta-Adrenoceptor agonists (dobutamine and dopamine)

Dopamine is a precursor of noradrenaline. It activates dopamine receptors and alpha- and beta-adrenoceptors. When administered by intravenous infusion, dopamine acts on:

  • Dopamine receptors, causing vasodilatation in the kidneys at low doses
  • alpha1-Adrenoceptors, causing vasoconstriction in other vasculature
  • beta1-Adrenoceptors, causing positive inotropic and chronotropic effects.

Dobutamine has no effect on dopaminergic receptors, but does activate beta1-adrenoceptors. If renal perfusion is not impaired, dobutamine and dopamine are a more appropriate means of treating shock than a-adrenoceptor agonists. This form of treatment maintains renal perfusion, and inhibits the activation of the RAS.

Route of administration

  • Indications: CCF (emergencies only), cardiogenic shock, septic shock, hypovolaemic shock, cardiomyopathy, cardiac surgery.
  • Contraindications: Tachyarrhythmias. Dopamine is contraindicated in people with phaeochromocytoma.
  • Adverse effects: Tachycardia and hypertension; dopamine causes nausea and vomiting and hypotension.
  • Therapeutic notes: Although low doses of dopamine cause vasodilatation, high doses cause vasoconstriction and may exacerbate heart failure.

Diuretics

Diuretics inhibit sodium and water retention by the kidneys, and so reduce oedema due to heart failure. Venous pressure and thus cardiac preload are reduced, increasing the efficiency of the heart as a pump. Spironolactone appears to have a beneficial effect in cardiac failure at doses lower than it would be expected to function as a diuretic.

Angiotensin-converting enzyme inhibitors

Captopril, enalapril, lisinopril and ramipril are examples of ACE inhibitors

Route of administration_Oral

  • Indications: Hypertension, heart failure and renal dysfunction (especially in diabetic patients to slowprogression of diabetic or reduced renal functional nephropathy).
  • Contraindications: Pregnancy, renovascular disease, aortic stenosis.
  • Adverse effects: Characteristic cough, hypotension, dizziness and headache, diarrhoea, muscle cramps.
  • Therapeutic notes: First-dose hypotension is relatively common, and should ideally be given just before bed.

Nitrates

The organic nitrates, glyceryl trinitrate (GTN), isosorbide mononitrate (ISMN) and isosorbide dinitrate (ISDN), can relieve angina within minutes.

Route of administration—Sublingual, oral (modified release), transcutaneous patches. GTN can be given by intravenous infusion.

  • Indications—Organic nitrates are given for the prophylaxis and treatment of angina, and in left ventricular failure.
  • Contraindications—Organic nitrates should not be given to patients with hypersensitivity to nitrates, or those with hypotension and hypovolaemia.
  • Adverse effects—Postural hypotension, tachycardia, headache, flushing and dizziness.
  • Therapeutic notes—To avoid nitrate tolerance, a drugfree period of approximately 8 hours is needed.

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