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