Quinidine metabolism

Ha HR, Chen J, Leuenberger PM, Ereiburghaus AU, Eollath E. In vitro inhibition of midazolam and quinidine metabolism by flavonoids. Eur J Clin Pharmacol 1995 48(5) 367-371. 

Quinidine Metabolism inducible. Inhibits CYP2D6. Renal excretion susceptible to changes in urine pH. Additive effects with other agents that prolong the QTC interval. Acetazolamide [P] Decreased renal quinidine excretion due to increased urinary pH elevated serum quinidine. 

Orally effective, often substituting for quinidine. Metabolized via N-acetyitransferase (genotypic variation) to AT-acetyl procainamide (NAPA), an active metabolite, which prolongs APD. With IV use, this is less likely to occur. 

Besides catalyzing styrene and benzaldehyde, CYP enzymes play an important role in the metabolism of endogenous compounds as well as in pharmacokinetics and toxicokinetics. Joseph [228] developed a biosensor with human CYP3A4 as a novel drugscreening tool. It was constructed by assembling enzyme films on Au electrodes by alternate adsorption of a layer of CYP3A4 on top of a layer of PDDA. The biosensor was applied to detect verapamil, midazolam, quinidine, and progesterone. 

The answer is b. (Hardmanr p 906.) Cimetidine reversibly inhibits cytochrome P450. This is important in phase I bio transformation reactions and inhibits the metabolism of such drugs as warfarin, phenytoin, propranolol, metoprolol, quinidine, and theophylline. None of the other enzymes are significantly affected. 

Use of a hERG blocker in a patient also taking CYP3A4 inhibitors (e.g. antibacterial macrolides, azole antifungals, HIV protease inhibitors) or CYP2D6 inhibitors (quinidine, halofantrine, fluoxetine, paroxetine, thioridazine, terbinafine) the hERG blocker, if mostly metabolized by these CYP isoforms, may accumulate because... 

Quinidine and anti-CVP2D6 antibody inhibit DXM metabolism in rat brain microsomes DXM metabolism shows significant regional variation (Tyndaie et al., 1999). 

DXM metabolism in rat brain microsomes is inhibited by quinidine and anti-CYP2D6 antibody human brain required exogenous reductase (Voirol et al., 2000). 

Quinidine (155) and dihydroquinidine (157) have been used for a long time for the treatment of cardiac antiarrythmia. These cinchona alkaloids (and their analogues in the quinine and cinchonidine family) are metabolized in animals and humans [234,235] to give, among several products, the corresponding (3S)-3-hydroxy derivatives (156,159) [236-240], which were shown to be pharmaco-... 

Metabolism/Excretion - From 60% to 80% of a dose is metabolized via the liver into several metabolites. Quinidine is excreted unchanged (10% to 50%) in the urine within 24 hours. The elimination half-life ranges from 4 to 10 hours in healthy patients, with a mean of 6 to 7 hours. Urinary acidification facilitates quinidine elimination, and alkalinization retards it. In patients with cirrhosis, the elimination half-life may be prolonged and the volume of distribution increased. 

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. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Bertelsen, K.M., Venkatakrishnan, K., Von Moltke, L.L., Obach, R.S. and Greenblatt, D.J. (2003) Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine comparison with fluoxetine and quinidine. Drug Metabolism and Disposition The Biolo cal Fate of Chemicals, 31, 289-293. 

Drugs that have been associated with elevations in quinidine concentrations include acetazolamide, the antacids magnesium hydroxide and calcium carbonate, and the H2-receptor antagonist cimetidine. Cimetidine inhibits the hepatic metabolism of quinidine. Phenytoin, rifampin, and barbiturates increase the hepatic metabolism of quinidine and reduce its plasma concentrations. 

Amiodarone increases the hypoprothrombinemic response to warfarin (an oral anticoagulant) by reducing its metabolism. Patients receiving digoxin may undergo an increase in serum digoxin concentrations when amiodarone is added to the treatment regimen. Amiodarone interferes with hepatic and renal elimination of flecainide, phenytoin, and quinidine. 

Itraconazole contraindicated in patients with evidence of ventricular dysfunction (CHF) or a history of CHF Itraconazole is also a potent inhibitor of cytochrome P450 3A4 isoenzyme, which may increase plasma concentrations of drugs metabolized by this pathway. Serious cardiovascular events have occurred in patients taking cisapride, pimozide, levomethadyl, or quinidine concomitantly with itraconazole. 

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