Anxiolytic drugs pharmacokinetics

Mahmood, I. and Sahajwalla, C. (1999) Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug. Clin Pharmacokinet 36 277-2 7. 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

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... 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

In principle, all drugs with damping action on the central nervous system could be used as anxiolytics or hypnotics, but the pharmacological and/or pharmacokinetic properties of most compounds are not appropriate for their therapeutic use ... 

Table 10.1 Pharmacokinetic properties of some anxiolytic and hypnotic drugs...

The individual benzodiazepines show small differences in their relative anxiolytic, anticonvulsant, and sedative properties. However, the duration of action varies widely among this group, and pharmacokinetic considerations are often important in choice of drug. 

The choice of drug as hypnotic and anxiolytic is determined by pharmacokinetic properties (see before, and Table 19.8). 

Although drug interactions may occur through a variety of mechanisms, most occur because of pharmacodynamic or pharmacokinetic interactions. Common examples of pharmacodynamic interactions resulting in enhanced effect include the excess sedation that can occur when antipsychotics are used concomitantly with other medications that have sedative side effects (e.g., mood stabUizers, hypnotics, alcohol, antidepressants, anxiolytics, or antihistamines). 

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