DIGOXIN
DIGOXIN
• Cardiac glycoside
• Inhibits magnesium dependent Na/K ATPase, resulting in increased intracellular Na and calcium with decreased K
• Has positive inotropic effect (increases strength of myocardial contraction) and negative chronotropic effect (reduces heart rate)
• Has low therapeutic index - small variations in dose can cause toxicity
• Excreted mainly by the kidneys (80%), although hepatic clearance becomes more important in renal failure. *Half life ~1-2 days with normal renal function.
• Toxicity increased by hypokalaemia (diuretics, beta-agonists, glucocorticoids) and hypomagnesaemia *
• Useful in the management of atrial fibrillation
TOXICITY
• Nausea, vomiting, diarrhoea
• Cardiac arrhythmias
• Blurred vision and disturbed colour vision
NIFEDIPINE - SIDE-EFFECTS *****
• Headache
• Hypotension and tachycardia
• Myocardial depression
• Constipation / diarrhoea
• Impotence and gynaecomastia
• Flushing (peripheral vasodilation) and peripheral oedema
• Increased frequency of micturiction
• Rash
• Gum hyperplasia and visual disturbance
NITRATES
• Glyceryl trinitrite, Isosorbide mononitrate
• Lipid soluble; nitric oxide (NO) donors
• NO acts by activating guanylate cyclase, resulting in increased cyclic GMP concentrations
• Cause smooth muscle relaxation - effect on veins / venules greater than the effect on arterioles, resulting in a greater reduction in cardiac pre-load
• Side-effects - flushing, sweating, headache, tachycardia, fainting
• Consumption of SH groups results in the development of tolerance
• GTN is rapidly inactivated by hepatic enzymes - sub-lingual administration is effective. ISMO is more stable and active orally
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