Drug metabolism thioridazine

Secondary> hyperparathyroidism 30 mg PO daily Parathyroid carcinoma 30 mg PO bid titrate q2—4wk based on Ca PTH levels swallow whole take w/ food Caution [C, /—] w/ Szs Disp Tabs SE N/V/D, myalgia, dizziness, 4- Ca2+ Interactions T Effects W/ CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin T effects OF drugs metabolized at CYP2D6 such as TCA, thioridazine, flecainide, vinblastine EMS Monitor ECG for signs of hypocalcemia (T QT interval) OD May cause severe hypocalcemia calcium salts can be given... 

Phenytoin induces hepatic microsomal drug-metabolizing enzymes and thus reduces concentrations of haloperidol (663,664), thioridazine (664), and tiotixene (665). In two patients phenytoin reduced plasma clozapine concentrations and worsened psychosis (666). 

Drugs that may be affected by duloxetine include drugs extensively metabolized by CYP2D6 (eg, flecainide, phenothiazines, propafenone, tricyclic antidepressants, thioridazine), alcohol, CNS-acting drugs, MAOIs, and drugs highly bound to plasma proteins (eg, warfarin). 

Maynard, G.L. and Soni, P. (1996) Thioridazine interferences with imipramine metabolism and measurement. Ther Drug Monit 18 729-731. 

Most antipsychotic drugs are readily but incompletely absorbed. Furthermore, many undergo significant first-pass metabolism. Thus, oral doses of chlorpromazine and thioridazine have systemic availability of 25-35%, whereas haloperidol, which has less first-pass metabolism, has an average systemic availability of about 65%. 

Various factors may account for the variability in response to neuroleptics. These include differences in the diagnostic criteria, concurrent administration of drugs which may affect the absorption and metabolism of the neuroleptics (e.g. tricyclic antidepressants), different times of blood sampling, and variations due to the different type of assay method used. In some cases, the failure to obtain consistent relationships between the plasma neuroleptic concentration and the clinical response may be explained by the contribution of active metabolites to the therapeutic effects. Thus chlorpromazine, thioridazine, levomepromazine (methotrime-prazine) and loxapine have active metabolites which reach peak plasma concentrations within the same range as those of the parent compounds. As these metabolites often have pharmacodynamic and pharmacokinetic activities which differ from those of the parent compound, it is essential to determine the plasma concentrations of both the parent compound and its metabolites in order to establish whether or not a relationship exists between the plasma concentration and the therapeutic outcome. 

The effects of neuroleptic drugs on serum lipids in adults have been reviewed (439). Haloperidol and the atypical neuroleptic drugs ziprasidone, risperidone, and aripipra-zole, are associated with lower risks of hyperlipidemia, whereas chlorpromazine, thioridazine, and the atypical drugs quetiapine, olanzapine, and clozapine are associated with higher risks. Treatment of the metabolic disturbances caused by neuroleptic drugs has also been reviewed (440). 

Nakagami T, Yasui-Furukori N, Saito M, Mihara K, De Vries R, Kondo T, Kaneko S. Thioridazine inhibits risperidone metabolism a clinically relevant drug interaction. J Clin Psychopharmacol 2005 25 89-91. 

TCAs HALOPERIDOL Possible t haloperidol levels Inhibition of CYP2D6- and CYP1 A2-mediated metabolism of thioridazine Warn patients to report t side-effects of these drugs... 

IMATINIB 1. ANTIARRHYTHMICS -flecainide, mexiletine, propafenone 2. ANTIDEPRESSANTS - fluoxetine, paroxetine, TCAs, trazodone, venlafaxine 3. ANTIPSYCHOTICS -clozapine, haloperidol, perphenazine, risperidone, thioridazine 4. BETA-BLOCKERS - metoprolol, propanolol, timolol 5. DONEPEZIL 6. METHAMPHETAMINE Imatinib may cause t plasma concentrations of these drugs, with a risk of toxic effects Inhibition of CYP2D6-mediated metabolism of these drugs Watch for early features of toxicity of these drugs... 

The possibility of an in vivo oxidation to the 5,5-dioxide has been considered. In the case of thioridazine, Zehnder et found a 5,5-dioxide among the metabolization products of this drug. Salzman and Brodie supposed that the 5,5-dioxide might be an advanced metabolic product of chlorpromazine, but this has been contes-... 

If patient is taking drugs that inhibit thioridazine metabolism, including CYP450 inhibitors... 

Mibefradil inhibits CYP3A4 (2). Other drugs that are metabolized by this pathway accumulate as a result. Drugs that were commonly affected included amiodarone, astemizole, ciclosporin, cisapride, erythromycin, imi-pramine, lovastatin, propafenone, quinidine, simvastatin (9), tacrohmus (10), tamoxifen, terfenadine, thioridazine, and drugs that impair sinoatrial node function (for example beta-blockers) (6). 

Maynard GL, Soni P. Thioridazine interferences with imi-pramine metabolism and measurement. Ther Drug Mouit 1996 18(6) 729-31. 

Sulfoxide drugs and metabolites may be further oxidized to sulfones (-SO2-). The sulfoxide group present in the immunosuppressive agent oxisuran is metabolized to a sulfone moiety. In humans, dimcthylsulfoxide (DMSO) is found primarily in the urine as the oxidized product dimethylsul-fone. Sulfoxide metabolites, such as those of thioridazine, reportedly undergo further oxidation to their sulfone -SO,-derivatives.3 ... 

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