Quinidine Digoxin

Fromm et al. [61] have shown in Caco-2 cells, that the apical to basolateral flux of digoxin is 1.2% per hour, and the basolateral to apical flux is 8.9% per hour. This polarized flux can be normalized by the addition of increasing concentrations of quinidine (with 100 pM quinidine, digoxin flux rates are 2.7% per hour apical to basolateral and 3% per hour basolateral to apical). Such a profile is indicative of... 

The quinidine-digoxin interaction has been reviewed (SEDA-6, 173) (SEDA-7, 195) (SEDA-9, 159) (SEDA-10, 145) (SEDA-15, 166) (SEDA-18, 198). 

Doering W. Quinidine-digoxin interaction Pharmacokinetics, underlying mechanism and clinical implications. N Engl J Med 1979 301(8) 400. ... 

Doering, W., Fichth, B., Hermann, M. Besenfelder, E. (1982) Quinidine-digoxin interaction Evidence for involvement of an extrarenal mechanism. European Journal of... 

Quinidine Digoxin Increased digoxin levels due to decreased clearance displacement may play a role... 

Quinidine reduces the renal excretion of digoxin by 40 to 50%, and it also appears to have some effects on non-renal clearance, which includes a reduction in digoxin excretion in the bile. There is also evidence that increases in the rate and extent of absorption of digoxin from the gut occur. More recent studies show that the mechanism behind these effects on absorption and renal excretion is likely to be P-glycoprotein inhibition by quinidine.Digoxin also appears to cause a small reduction in the renal clearance of quinidine. Quinidine appears to increase digitoxin serum levels by reducing its non-renal clearance. 

Fichtl B, Doering W. The quinidine-digoxin interaction in pei >ective. CUn Pharmacokinet (1983) 8, 137-54. 

RameisH. Quinidine-digoxin interaction are the pharmacokinetics ofboth drugs altered ... 

The co-administration of drugs which inhibit the transporters involved in biliary excretion can reduce the biliary excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, biliary and urinary excretion of digoxin, both mediated by P-gp, are inhibited by quinidine which is an inhibitor of P-gp. 

Digoxin Inhibits AV nodal conduction by 1. Vagal stimulation 2. Directly slowing AV nodal conduction and prolonging AV nodal refractoriness 0.25 mg every 2 hours up to 1.5 mg 0.125-0.25 mg PO once daily Amiodarone, verapamil, quinidine inhibit digoxin elimination... 

P-gp-mediated transport. These authors underlined their results with P-gp knockout mice studies. Co-administration of digoxin and quinidine to wild-type mice resulted in a 73% increase in digoxin concentrations, whereas the increase for the knockout mice was only 20%. 

Fromm, M. F., Kim, R. B., Stein, M., Wilkinson, G. R., Roden, D. M., Inhibition of P-glycoprotein-mediated drug transport a unifying mechanism to explain the interaction between digoxin and quinidine, Circulation 1999, 99, 552-557. 

Angiotensin-converting enzyme inhibitors Cholinergics Bethanechol Neostigmine Cardiac agents Quinidine Digitalis Digoxin... 

Cardiac agents (digoxin, diuretics, hypotensives, quinidine)... 

Maintenance dose 0.125-0.25 mg PO/IV qd low potassium or magnesium levels potentiate toxicity reduce dose in renal failure toxicity indicated by nausea, headache, visual disturbances (yellow-green halos), ventricular arrhythmias. Quinidine, verapamil, and amiodarone elevate digoxin level. 

Digoxin uptake into rat hver shces showed a temperature-dependent component, compatible with the involvement of carrier-mediated uptake mechanisms. Quinine markedly inhibited the uptake of digoxin, in contrast to its diastereomer quinidine, which only slightly inhibited the digoxin uptake in rat liver slices. This stereoselective inhibition is in line with results obtained in isolated rat hepatocytes and isolated perfused rat hvers [90,91]. These results were also found after cryopreservation of the slices, indicating that carrier-specific phenomena can be studied after cryopreservation [92]. 

Drugs that may affect disopyramide include antiarrhythmics, beta blockers, cisapride, clarithromycin, erythromycin, fluoroquinolones, hydantoins, quinidine, thioridazine, rifampin, verapamil, and ziprasidone. Drugs that may be affected by disopyramide include quinidine, anticoagulants, and digoxin. 

Drugs that may affect amiodarone include hydantoins, cholestyramine, fluoroquinolones, rifamycins, ritonavir, and cimetidine. Drugs that may be affected by amiodarone include anticoagulants, beta-blockers, calcium channel blockers, cyclosporine, dextromethorphan, digoxin, disopyramide, fentanyl, flecainide, hydantoins, lidocaine, methotrexate, procainamide, quinidine, and theophylline. Drug/Lab test interactions Amiodarone alters the results of thyroid function tests, causing an increase in serum T4 and serum reverse T3 levels and a decline in... 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

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