Drug metabolism venlafaxine

These types of antidepressant were introduced around 10 years after the SSRIs. They include the serotonin noradrenaline reuptake inhibitor venlafaxine and the selective noradrenaline reuptake inhibitor reboxetine. Although there are fewer data about these drugs, clinical experience has shown they are well tolerated and, unlike the SSRIs, they are only weak inhibitors of drug metabolism (Kent, 2000). Depression is a common psychiatric disorder seen in the elderly and often remains untreated or inadequately treated (Forsell and Fastbom, 2000). Venlafaxine was shown to improve the mood in a group of 36 older patients without any effect on cognitive function, an important consideration where there is the possibility of the coexistence of mild or undiagnosed dementia (Tsolaki et al., 2000). 

Single-dose venlafaxine does not alter the single-dose pharmacokinetic profile of drugs metabolized by CYP3A4 (alprazolam and diazepam). When milnacipran was administered with lorazepam in healthy volunteers, no changes in the pharmacokinetics of any drug were detected. 

Fluvoxamine inhibits liver drug-metabolizing enzymes. Dosages of alprazolam, theophylline, and warfarin must be reduced if any of these drugs are given concomitantly with fluvoxamine. Nefazodone may also decrease the metabolism of benzodiazepines, and venlafaxine may inhibit haloperidol metabolism. The answer is (B). 

Both venlafaxine and trimipramine can cause seizures, although usually after overdose. Either a pharmaeokinetic interaetion involving inhibition of drug metabolism by the isoenzyme CYP2D6, or a pharmacodynamic interaction may have resulted in seizures. ... 

Venlafaxine is metabolized to its active metabolite, ODV, by cytochrome P-450 2D6. Therefore, the potential exists for a drug interaction between venlafaxine and drugs that inhibit this isoenzyme. 

Because most antidepressants require oxidative metabolism as a necessary step in their elimination, they can be the target of a pharmacokinetic drug-drug interaction, as well as the cause. The CYP enzymes mediating the biotransformation of the various antidepressants are also shown in Table 7-30. CYP 1A2 and 3A3/4 are induced by anticonvulsants such as barbiturates and carbamazepine. As expected, coadministration of these anticonvulsants has been shown to lower plasma levels of TCAs and would be predicted to have the same effect on nefazodone, sertraline, and venlafaxine. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

MAOIs DULOXETINE, VENLAFAXINE Risk of severe hypertensive reactions and of serotonin syndrome > For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. Due to impaired metabolism of these amines, there is an accumulation of serotonin and norepinephrine in the brain and at peripheral sites Do not co-administer duloxetine and venlafaxine prior to 14 days after discontinuing an MAOI, and do not co-administer MAOI for 5 days after discontinuing duloxetine, 1 week after venlafaxine... 

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... 

CANNABIS SERTRALINE, VENLAFAXINE Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

Drugs used in the treatment of depression and psychosis can alter the metabolism of terfenadine. When the antidepressant venlafaxine was given to steady state (37.5 mg bd for 3 days and then 75 mg bd for 5 days), the pharmacokinetics of a single dose of terfenadine 120 mg were not altered and there were no changes in the electrocardiogram (13). The authors concluded that cardiotoxicity is unlikely to arise with co-administration of terfenadine and venlafaxine. 

At steady state, venlafaxine weakly inhibits the metabolism of risperidone however, this interaction is unlikely to be of clinical significance. Co-administration of milnacipran and levomepromazine increases the milnacipran plasma concentration because of a modification of the apparent total clearance of the drug. 

This drug significantly increases the plasma concentration of venlafaxine. The oral clearance of diphenhydramine, in both extensive and reduced metabolizers, is reduced by 6% and 18%, respectively. 

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