Ans: a (Na K ATPase) Ref: Tripathi, 6th ed, p. 499All cardiac glycosides are potent and highly selective inhibitors of the active transport of Na+ and K+ across cell membranes by their reversible binding to the alpha subunit of the. Na+, K+- ATPase the elimination 11 /2 for digoxin is 36 hours in patients with nonnal renal function. Digoxin is excreted by the kidney with a clearance rate that is proportional to the glomerular filtration rate. It is now recommended that digoxin be reserved for patients with heart failure who are in atrial fibrillation, or for patients in sinus rhythm who remain symptomatic despite maximal therapy with ACE inhibitors and beta adrenergic receptor antagonists. Although the drug has no net effect on mortality, it reduces hospitalization and death, from progressive heart failure at the expense of an increase in sudden death.Other than heart failure digitalis is useful in the management of atrial arrhythmias because of its cardioselective parasympathomimetic effects. In atrial flutter and fibrillation, the depressant effect of the drug on atrioventricular conduction will help control an excessively high ventricular rate. Digitalis has also been used in the control of paroxysmal atrial and atrioventricular nodal tachycardia.ToxicityExtracardiacAnorexia, nausea, vomiting are usually first symptoms of toxicity. Other complaints include fatigue, malaise, headache, mental confusion, restlessness, disorientation, psychosis and visual disturbances.CardiacAlmost every type of arrhythmia can be produced by digitalis: pulsus bigeminis, nodal and ventricular extrasystoles, ventricular tachycardia and fibrillation. Partial to complete A-V block, severe bradycardia.Atrial extra systoles, AF or atrial flutter have also been noted.Treatmenta) For tachyarrythmias:KC1 infusion 20 m mol /hr IV or give orally in mild cases.b) For ventricular arrythmias: Lidocaine IV repeated as required is the drug of choice.c) For supraventricular arrythmias: Propranolol may be given IV or oral depending on urgencyd) For A-V block and bradycardia: Atropine 0.6-1.2 mg IM may help: otherwise cardiac pacing is recommended.Therapy of toxicity manifested as visual changes or gastrointestinal disturbances generally requires no more than reducing the dose of the drug.Immunotherapy with purified Fab fragments from bovine antidigoxin antisera (DIGIBIND) provides an effective antidote for lifethreatening digoxin toxicity.Precautions and contraindicationsHypokalaemia:enhances digitalis toxicityby increasing its binding to Na+ K+ATPase elderly, renal or severe hepatic disease Myocardial infarction: sever arrythmias are more likely thyrotoxicosis-reduces responsiveness to digitalis.Myxedema: these patienst eliminate digoxin more slowly, toxicity can appearVentricular tachycardia:digitalis is contraindicated, may precipitate ventricular fibrillationIt is explicitly contraindicated in patients with Wolff-Parkinson-White syndrome and atrial fibrillation