Antidepressant drugs therapeutic plasma concentration

The answer is a. (Hardman, p 436J The most common side effects associated with tricyclic antidepressants are their anti muscarinic effects, which may be evident in over 50% of patients. Clinically, the anti muscarinic effects may manifest as dry mouth, blurred vision, constipation, tachycardia, dizziness, and urinary retention. At therapeutic plasma concentrations, these drugs usually do not cause changes in the EKG Direct cardiac effects of the tricyclic antidepressants are important in over dosage. 

Tricyclic antidepressants Despite the numerous publications over the past 30 years on the determination of the TCAs (Tricyclic Antidepressants) by HPLC to establish possible therapeutic windows, both therapeutic drug monitoring and pharmacokinetic calculations have revealed there is considerable variation (10- to 50-fold) in plasma concentrations between individuals with these drugs. The plasma concentrations are usually in the range of 50-300 ng/ml. 

In SUMMARY, it would appear that a detailed knowledge of the pharmacokinetics of the main groups of psychotropic drugs is only of very limited clinical use. This is due to limitations in the methods for the detection of some drugs (e.g. the neuroleptics), the presence of active metabolites which make an important contribution to the therapeutic effect, particularly after chronic administration (e.g. many antidepressants, neuroleptics and anxiolytics), and the lack of a direct correlation between the plasma concentration of the drug and its therapeutic effect. Perhaps the only real advances will be made in this area with the development of brain imaging techniques whereby the concentrations of the active drug in the... 

While effects of P-glycoprotein polymorphisms have been reported for intestinal uptake, no such studies exist for effects on blood-brain barrier penetration. If certain polymorphisms were to alter intracerebral concentrations of specific antidepressants, prior knowledge of the patients relevant P-glycoprotein genotypes could prevent the administration of a drug that might never reach therapeutic intracerebral levels despite a normal plasma concentration. 

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. 

IRINOTECAN 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS -St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentrations of irinotecan and risk of 1 therapeutic efficacy. The effects may last for 3 weeks after discontinuation of CYP-inducer therapy Due to induction of CYP3A4-mediated metabolism of irinotecan Avoid concomitant use when ever possible if not, t dose of irinotecan by 50%... 

Several LC-MS and LC-MS/MS methods were developed in plasma for only one antidepressant and, sometimes, its major metabolite(s) to perform pharmacokinetic, bioavailability, or bioequivalence studies. Analytical methods developed for these purposes require very low LLOQ values and, usually, narrow linear ranges covering the low range of the therapeutic concentrations are validated. In this context, several methodologies were described for the determination of fluoxetine [94, 95, 98-100], paroxetine [44, 71, 85, 101, 102], venlafaxine [48, 61, 64, 86, 103,104], sertraline [62, 68, 83], citalopram [46, 89] and escitalopram [105], mianserine [106, 107], mirtazapine [42], trazodone [84], nefazodone [51, 81], duloxetine [47, 50, 73], and bupropion [43], Deuterated analogues of the analyte of interest or of other drugs were employed by few authors as IS [43, 61, 73, 81, 85, 99] however, in most of these methods, another antidepressant or other therapeutic drug was used for this purpose. 

Plasma levels of some of the tricyclic antidepressants can be measured by clinical laboratories. Therapeutic concentrations are usually less than 0.3 mg/L (300 ng/mL). Total concentrations of parent drug plus metabolite of 1 mg/L (1000 ng/mL) or greater are usually associated with serious poisoning. Generally, plasma levels are not used in emergency management because the QRS interval and clinical manifestations of overdose are reliable and more readily available indicators of toxicity. 

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