Nicotine Cimetidine

FAD dependent oxidation of nucleophilic nitrogen, sulfur and phosphorus heteroatoms, e.g. conversion of nicotine to nicotine l -iV-oxide, cimetidine to cimetidine S-oxide... 

In vitro stndies have shown that there are distinct transport systems for both baso-lateral and apical uptake of nicotine (Takami et al. 1998). Nicotine has been shown to be actively transported by kidney cells, most likely by the organic ion transporter OCT2 (Zevin et al. 1998 Urakami et al. 1998). Cimetidine decreases renal clearance of nicotine by 47% in nonsmoking volunteers (Bendayan et al. 1990). This is consistent with the inhibition of basolateral uptake by cimetidine detected in vitro. Mecamylamine reduces renal clearance of nicotine in smokers dosed with intra-venons nicotine when urine is alkalinized, but not when nrine is acidified (Zevin et al. 2000). 

Bendayan R, SuUivan JT, Shaw C, Erecker RC, Sellers EM (1990) Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans. Eur J Chn Pharmacol 38(2) 165-169... 

Drugs that may affect HMG-CoA reductase inhibitors include alcohol, amiodarone, antacids, azole antifungals, bile acid sequestrants, cimetidine, cyclosporine, diltiazem, erythromycin, gemfibrozil, isradipine, nefazodone, niacin, nicotinic acid, omeprazole, phenytoin, propranolol, protease inhibitors, ranitidine, rifampin, St. John s wort, and verapamil. 

Drugs eliminated via renal mechanisms Coadministration of drugs that use the same renal cationic system, including hydrochlorothiazide (HCTZ), triamterene, cimetidine, ranitidine, quinidine, and nicotine, potentially could result in altered plasma levels of both agents. 

Nicotine Nasal Spray (Nicolrol NS) [Smoking Deterrent/ Cholinergic] Uses Aid to smoking cessation, relieve nicotine withdrawal Action Systemic delivery of nicotine Dose 0.5 mg/actuation 1-2 sprays/h, 10 sprays/h max Caution [D, M] Contra Life-threatening arrhythmias, unstable angina Disp Nasal inhaler SE Local irritation, tach, HA, taste p v sion Interactions T Effects W/ cimetidine, black cohosh t effects OF catecholamines, cortisol T hemodynamic AV blocking effects OF adenosine EMS See Nicotine Gum OD See Nicotine Gum... 

Taken with alcohol they potentiate the sedative effects and impairment of psychomotor performance. Hepatic enzyme induction by barbiturates or nicotine may reduce plasma levels. Cimetidine may increase levels by enzyme inhi bition. Some antipsychotic drugs may compete for similar metabolic pathways. 

Nicotine is an example of a compound that undergoes FM03-catalyzed N-oxidation, as shown in Scheme 11.27. About 4% of nicotine is stereoselec-tively metabolized to trans-(S)-(—)-nicotine N-V oxide in humans by FM03, whereas 30% of an administered dose appears as cotinine, a CYP2A6 product (34, 35). Other examples of FMO N-oxidation include trimethylamine, amphetamine, and the phenothi-azines (33). As described previously, FM03 catalyzes S-oxidation of substrates such as cimetidine, shown in Scheme 11.28, and chlorpromazine, also a CYP3A substrate (Scheme 11.22). 

Octi (Slc22al) Rat TEA, MPP+, NMN, monoamine neurotransmitters Drugs AZT, cimetidine, cladribine, cytambine, D-tubocurarine Corticosterone, guanidine, histamine, nicotine, o-methylisoprenaline Drugs clonidine, desipramine, mepiperphenidol, procainamide, reserpine, quinine, quinidine... 

CTN1 (SLC22A4) Human TEA, MPP+, L-carnitine, acetyl-L-carnitine Drugs pyrilamine, quinidine, verapamil D-carnitine, nicotine Drugs cephaloridine, cimetidine, procainamide, quinine... 

Octnl (Slc22a4) Rat TEA, MPP+ DMA, nicotine Drugs cimetidine, desipramine, imipramine, procainamide, verapamil... 

Octi Acyclovir, AZT, ganciclovir, indinavir, ritonavir, nelfinavir, saquinavir, amantandine, desipramine, nicotine, procainamide, vecuronium, cimetidine, clonidine, prazosin, reserpine, verapamil... 

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