Sedative Hypnotics and Antianxiety Drug

GABA (γ-aminobutyric acid), is a Cl- ion channel
• Activated by GABA, inhibitory neurotransmitter in the CNS.- five subunits (α, β, and γ)- “GABA-A” isoform consists of two α1, two β2, and one γ2 subunits - 2 GABA binds at two locations between adjacent α1 and β2 subunits.

Sedatives-hypnotics bind GABA-A receptors in the CNS.

Antidepressants-

Selective serotonin reuptake inhibitors (SSRIs, such a escitalopram).

Selective serotonin&norepinephrine reuptake inhibitors(venlafaxine).

Lower potential for physical dependence than benzodiazepines-became first-line treatment for generalized anxiety disorders.

First-line agents in patients with concerns for addiction or dependence or a history of addiction or dependence to other substances.

Buspirone

Useful for the chronic generalized anxiety disorder

partial agonist of serotonin (5-HT1A) receptors and has affinity for
brain dopamine D2 receptors & 5-HT2A serotonin receptors.

adverse effects is low , NO anticonvulsant and muscle-relaxant properties, minimal sedation,psychomotor and cognitive dysfunction , No withdrawal symptoms & dependence, It does not potentiate the CNS depression of alcohol.

disadvantage of a slow onset of action.

Not effective for short-term or “as-needed” treatment of acute anxiety

Barbiturates

negative properties

At high doses, may act as a GABA-mimetic, directly activating chloride channels.

block excitatory glutamate AMPA receptors.

block high-frequency sodium channels


Classification

Pentobarbital, Secobarbital, Amobarbital- Short-acting barbiturates that are effective as sedatives and hypnotics (but not antianxiety).

Phenobarbital - Long-acting – duration of action > 1 day- used to treat seizures.

Thiopental - Ultra-short acting – Given IV for induction of anesthesia.


Therapeutic uses

Anticonvulsant: Phenobarbital used in long-term management ,

Anxiety:

Anesthesia : thiopental

Barbiturates induce P450 system-


Z-drugs

Zolpidem, Zaleplon, Eszopiclone

benzodiazepine receptor family, BZ1.

no muscle-relaxing properties and no anticonvulsant effects.
• Few withdrawal effects, minimal rebound insomnia, little or no tolerance.


Ramelteon

Selective agonist at melatonin receptors MT1 & MT2 , induces and promotes sleep

treatment of insomnia, Can be administered long-term- potential for abuse is minimal- no evidence of dependence or withdrawal effects


Chloral Hydrate

short-term treatment of insomnia and as a sedative before minor medical or dental treatment.

very narrow therapeutic window. High doses depress respiration & BP.

active metabolite- Trichloroethanol.

unpleasant taste & is irritating to GI tract and causes epigastric distress

Antihistamines

1st generation antihistamines have sedating properties.

side effect : anticholinergic effects)

Ethanol

Ethanol synergizes with many other sedative agents producing severe CNS depression - benzodiazepines, antihistamines, or barbiturates

Disulfiram:

Naltrexone

Acamprosate