Benzodiazepines pharmacological effects

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

Otherwise, if benzodiazepines are combined with disulfiram the pharmacologic effect may be greater than expected, and the dose of benzodiazepine may need to be lowered. 

As with all of the examined drugs in this chapter, methyprylon is intended for treating insomnia. The pharmacological effects of methyprylon are similar to those of barbiturates. However, barbiturates are beginning to give way, thanks to the introduction of benzodiazepines into medical practice. Synonyms for this drug are noctar, noludar, and others. 

Zolpidem (1) is an effective hypnotic agent indicated for the short-term treatment of insomnia. Zolpidem interacts with the GABAa receptor, and its pharmacological effect is blocked by the benzodiazepine-receptor antagonist fiumazenil (Sanger and Depoortere, 1998). Zolpidem displaces benzodiazepines more selectively from the cerebellum than the hippocampus or spinal cord, consistent with preferential interaction with the ajGABAA receptor subtype (sometimes referred to as the benzodiazepine coi receptor). Studies... 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

Benzodiazepines exert their pharmacological effect mainly by potentiation of neural inhibition in CNS which is mediated by GABA. 

Vgontzas AN, Kales A, Bixler EO. Benzodiazepine side effects role of pharmacokinetics and pharmacodynamics. Pharmacology 1995 51 205-223. 

Benzodiazepines are a family of compounds that share the same basic chemical structure and pharmacological effects. Although the more famous members of this family are associated with treating anxiety (e.g., diazepam [Valium] see later in this chapter), several benzodiazepines are indicated specifically to promote sleep (Table 6-1). These agents exert hypnotic effects similar to those of nonbenzodiazepines—such as the barbiturates—but benzodiazepines are generally regarded as safer because there is less of a chance for lethal overdose.22 Benzodiazepines, however, are not without their drawbacks, and they can cause resid-... 

The formation of active metabolites has complicated studies on the pharmacokinetics of the benzodiazepines in humans because the elimination half-life of the parent drug may have little relationship to the time course of pharmacologic effects. Those benzodiazepines for which the parent drug or active metabolites have long half-lives are more likely to cause cumulative effects with multiple doses. Cumulative and residual effects such as excessive drowsiness appear to be less of a problem with such drugs as estazolam, oxazepam, and lorazepam, which have shorter half-lives and are metabolized directly to inactive glucuronides. Some pharmacokinetic properties of selected benzodiazepines are listed in Table 22-1. 

In CONCLUSION, evidence has been presented to show that the benzodiazepines produce their variety of pharmacological effects by activating specific receptors that form part of the main inhibitory neurotransmitter receptor system, the GABA receptor, in the mammalian brain. Different classes of benzodiazepine receptor ligands have been developed which can alleviate anxiety or produce anxiety according to the fine structural changes that occur when the drugs interact with the benzodiazepine receptor. 

For the acute relief of anxiety or panic attacks, benzodiazepines are often useful, usually on an as-needed basis. Many clinicians are reluctant to prescribe these medications for an extended period of time (due to risks associated with physiologic dependence, withdrawal, or abuse), but for the relief of acute symptoms, benzodiazepines are a valuable therapeutic modality. Although a wide variety of benzodiazepines are currently available, they are all qualitatively similar in terms of their pharmacologic effects and side effect potential. Clonazepam and alprazolam are the two benzodiazepines used most commonly to treat anxiety disorders. 

Benzodiazepine receptors are present in the cerebral cortex, thalamus, hippocampus, hypothalamus, cerebellar cortex and spinal cord. Each of the major pharmacological effects of benzodiazepines is attributable to the effect of the benzodiazepines on chloride charmels at these sites in the CNS sedation, muscle relaxation and an anticonvulsant effect. In humans, they are considered effective anxiolytics and they produce amnesia. 

Benzodiazepines exert multiple pharmacologic effects on CNS structures, including sedation, hypnosis, decreased anxiety, muscle relaxation, and anticonvulsant activity. 

Benzodiazepines get attached to receptor sites that are highly specific. By combining with receptor sites, they elicit a pharmacologic effect. 

A wide difference in milligram potency exists between the benzodiazepine compounds however, when dosage adjnstments are made, all agents share similar anxiolytic and sedative-hypnotic activity. The variations in lipid solubility between componnds inflnence the pharmacokinetic properties of benzodiazepines. Different pharmacokinetic and pharmacodynamic properties can assist the clinician in choosing an appropriate anxiolytic (Table 69-9). After a single dose, the onset, intensity, and duration of pharmacological effects are important factors to consider when using benzodiazepines for the short-term, intermittent, or as-needed treatment of anxiety. 

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