Cardiac glycosides drug interactions with

Drug interactions with cardiac glycosides can be subdivided into six types, according to mechanism. Interactions with digoxin have been reviewed (SEDA-6, 173) (196-198). Drug interactions with digitoxin have been briefly reviewed in the context of its use in the treatment of congestive heart failure (199). 

Antman EM, Arnold M, Friedman PL, White H, Bosak M, Smith TW. Drug interactions with cardiac glycosides evaluation of a possible digoxin-ethmozine pharmacokinetic interaction. J Cardiovasc Pharmacol 1987 9(5) 622-7. 

If 50% of Europeans with essential hypertension are affected by this disease because of an elevated secretion of endogenous ouabain, then there might be a chance to block its interaction at the cardiac glycoside binding site of Na+/K+-ATPase and thus lower blood pressure. This therapeutic approach seems to be successfiil. Recent studies provide evidence that the cardenolide analogue Rostafuroxin (PST 2238 Fig. 4) at very low concentrations can overcome the ouabain-induced tise of hypertension in experimental animals [6]. This compound has recently entered the phase I of clinical trials and is certainly a prototype of a new class of antihypertensive drugs. 

Other drugs that may interact with cardiac glycosides include the following Albuterol, amphotericin B, beta-blockers, calcium, disopyramide, loop diuretics, nondepolarizing muscle relaxants, potassium-sparing diuretics, succinylcholine, sympathomimetics, thiazide diuretics, thioamines, and thyroid hormones. 

Cardiac glycosides interact with many other drugs some increase the risk of toxicity (for example amiodarone and verapamil) and others reduce it (for example cholestyramine, colestipol and antacids), but also reduce therapeutic effect. 

Established interactions. The CSM in the UK advises that, as potentially serious hypokalaemia may result from beta2 agonist therapy, particular caution is required in severe asthma, as this effect may be potentiated by theophylline and its derivatives, corticosteroids, diuretics, and by hypoxia. Hypokalaemia with concurrent use of thiazide and loop diuretics may be reduced or even abolished by the addition of spironolactone or high-dose triamterene. Plasma potassium levels should therefore be monitored in patients with severe asthma. Hypokalaemia may result in cardiac arrhythmias in patients with ischaemic heart disease and may also affect the response of patients to drugs such as the digitalis glycosides and an-tiarrhythmics. 

Except for the fact that the interaction of cardiac glycoside with the Na K ATPase is very complex, the mode of inhibition of the enzyme by these drugs is not understood. 

V. Drug or laboratory interactions. The positive inotropic effects of inamrinone are additive with other inotropic agents, including digitalis glycosides. These drugs can be used together, but the patient should be monitored for cardiac dysrhythmias. 

The weakening or even loss of potency in such derivatives of C[D-trans steroids has led to the tacit opinion that CfD-trans steroids as such cannot elicit inotropic activity and serve as potential cardiac drug candidates. Most remarkably, however, certain steroid representatives with trans junction of the rings C and D have recently been demonstrated to evolve similar or even higher interaction energies with human NaVK -ATPase compared with their CfD-cis counterparts [88]. This discovery has prompted studies on the impact of glycosidation on the biological activity of CfD-trans steroids in view of their possible suitability to serve as a novel type of pharmacophoric lead structure [22,183,184]. This is evaluated below. 

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