Cardiac Drugs in Heart Failure Patients Zoulikha Zair 28 th May 2013 N.B. some drugs overlap with treatment of hypertension….bonus revision wise!!!!

Question What are the NICE guidelines for the pharmacological treatment of left ventricular heart failure?

Answer NICE guidelines for treatment of LV heart failure: Diuretic - relief of congestive symptoms and fluid retention AND First line: – ACE-inhibitors or – Beta-Blockers Second line: – Add Aldosterone antagonist Angiotensin receptor antagonist Hydralazine with nitrate Third line: – Consider digoxin

Question How do ACE-inhibitors work? What are their side effects? Name a commonly used ACE-inhibitors

Answer ACE – inhibitor  vasodilator – Inhibits bradykinin breakdown (vasodilator) – Inhibits angiotensin converting enzyme  inhibits angiotensin II production Side effects – dry cough, elevated K levels, birth defects, low blood pressure Ramipril

Question How do ARBs work? What are their side effects? Name a commonly used ARB

Answer Inhibit action of Angiotensin II Reduce vascular resistance  Restore tissue perfusion  Reduce afterload Reduce aldosterone production  Natriuresis Hypotension, renal impairment, hyperkalaemia, angioedema Losartan

Question How do beta-blockers work? Name a selective beta1 blocker What are the unwanted side effects?

Answer Beta blockers reduce sympathetic stimulation of the heart by blocking beta-1 adrenergic receptors (Gs coupled  cAMP increase) in the heart – Reduced sympathetic stimulation also reduces arterial pressure and decrease cardiac contractility Dobutamine Unwanted side effects – increase left ventricular dimensions, cold periphery and heart failure

Question What is the mechanism of action for aldosterone antagonists? What are the side effects of aldosterone? Name an aldosterone antagonist

Answer Blocks action of aldosterone at DCT  Increase Na + and water excretion K + -sparing diuretic Especially effective combined with ACE-I / ARB Hyperkalaemia, gynaecomastia (only in some), hypotension, hypernatraemia, GI upset, impotence Eplerenone, spirnonolactone

Question What is the mechanism of action for hydralazine? What are the side effects of hydralazine?

Answer Unknown mechanism of action Dilates arteries & arterioles,  afterload s/e: Tachycardia, GI upset, headache, lupus-like syndrome

Questions How do nitrovasodilators work? What are the unwanted side effects and problems?

Answers Metabolised to NO  activate guanylate cyclase  increase in cGMP  fall in intracellular free calcium  vascular relaxation  increase in venous capacitance  fall in central venous pressure  reduce preload  reduction in ventricular dimensions and cardiac output Side effect – headache due to dilatation of intracranial arteries Also problem with quickly developing tolerance that can lead to abnormal constriction of coronary arteries following withdrawal – Either inactivated enzyme that converts GTN to NO or desensitisation of blood vessels to NO

Vascular Drugs