Anxiolytics and hypnotics

Benzodiazepines BDZs The most important group and widely used group in the treatment of anxiety and insomnia. They selectively bind to the GABAA receptors which mediate inhibitory effects in the CNS. BDZs enhance the response to GABA by facilitating the opening of GABA activated chlorine channels.

Benzodiazepines.
They bind to a regulatory site different from the normal GABA binding site and act to increase the affinity of GABA for the receptor. Benzodiazepines thus act to increase the frequency of chlorine channel opening but no change in the opening time.

BDZs
Therapeutic uses include the following Anxiolytic Anti-epileptic Hypnotics Reduction in muscle tone and co-ordination With the exception of Alprazolam they do not have effect on depressed patients.

 BDZs reduce time taken to sleep and also tend to increase the total sleeping time thus is useful in the treatment of insomnia. All BDZs have an anticonvulsant effect. They are highly effective against chemically induced convulsions (Pentylenetetrazol) They have effect on GABA not Glycine receptors

 Diazepam and Clonazepam exhibit anticonvulsive effects Classified into short-acting medium-acting and long-acting. Have a high lipid affinity and tend to accumulate in fat cells. After oral admin they are almost fully absorbed from the GIT.

 May also be given IV and IM Short acting; lorazepam, midazolam, oxazepam Medium acting; alprazolam, nitrazepam Long acting; diazepam, clonazepam, flurazepam

Side effects
Tolerance and dependence Drowsiness, confusion, amnesia, reduced motor co-ordination Short acting BDZs cause quick withdrawal symptoms compared to longer actings.

5-HT1A agonists
Buspirone is a typical and clinically important member of this group. It is a partial agonist at the receptor. 5-HT1A recptors are autoinhibitory receptors that reduce the release of 5-HT and other mediators. Very slow to exert full effects taking weeks before maximum effects thus has a complex mechanism of action

Buspirone.
Ineffective in the treatment of panic attacks orsevere anxiety states No motor disturbances, withdrawal effects or sedation experienced, however its main side effects are dizziness, nausea and headaches.

Barbiturates.
Barbiturates enhance GABA activity. They bind to a GABA receptor different from the BDZ receptor. They act after binding to the GABA chlorine channel to increase the mean opening time of the GABA chlorine channels. Cause severe respiratory depression, dependence and tolerance compared to BDZs.

Barbiturates.
Mainly used barbiturate is phenobarbitone but their use as anxiolytics or hypnotics is becoming obsolete.

SSRIs.
Fluoxetine, paroxetine, sertraline. Mainly used as anti-depressants but their anxiolytic action is independent of their antidepressant effect TCA (Amitriptylline) may also be used as an hypnotic as well as being an anti-depressant.

 Sedating anti-histamines e.g. promethazine are safe hypnotics for ocassional insomnia. Zopiclone and zolpidem act on the benzodiazepine receptors but are not BDZs themselves. Propranolol may be effective in alleviating the autonomic symptoms of anxiety e.g. muscle tremor, restlessness, sweating