The traditional dose-response method of medication adjustment depends on several assumptions that are not met in the case of tricyclic antidepressants (TCAs), which makes therapeutic drug monitoring (TDM) particularly useful with these drugs. TDM can facilitate treatment by providing objective guidelines for dose adjustment. It provides a means of assessing compliance, ensuring an effective concentration, and avoiding toxicity. The latter is an often-overlooked benefit of therapeutic monitoring of TCAs and yet is just as important as improving response. The cardiac and central nervous system toxicity of TCAs is concentration-dependent and potentially life-threatening. Such toxicity will predictably occur in up to 5% of patients on standard antidepressant doses of TCAs when TDM is not used to rationally adjust the dose. Without TDM, such toxicity is difficult to detect early. A cost/benefit analysis supports the cost effectiveness of TDM as a standard part of TCA chemotherapy when doses in the 100-300 ng/day range are used.
The Ion Trap Detector (ITD) is being increasingly demonstrated as a versatile design, allowing electron impact (EX) and chemical (CI) ionization, and even the promise of MS/MS capability. Laboratories are beginning to utilize the design as a low-cost alternative to the familiar quadruple mass filter. In many cases, spectra from an ITD are virtually identical to those produced in a quadrupole mass spectrometer, but this cannot always be assumed. This report presents a significant example of CI mass spectra using a ITD which are totally unlike those from a conventional instrument. The example here is the methane CI mass spectrum of tetradecane, although the mass spectra of all n-alkanes which we have examined with the ITD show the same characteristics.
We investigated the effect of disulfiram (Antabuse) on the activity of alcohol dehydrogenase (EC 1.1.1.1) in vitro. We observed a time-dependent inhibition of this dehydrogenase by disulfiram and diethyldithiocarbamate similar to that obtained for aldehyde dehydrogenase (EC 1.2.1.3). These results suggest a possible explanation for various side effects observed in the clinical use of Antabuse.
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