Anxiolytic and Hypnotic Drugs Quiz

Anxiolytic and Hypnotic Drugs

• Benzodiazepines are widely used anxiolytic drugs, considered safe and effective.
• Mechanism of action: Benzodiazepines act on GABA receptors.
• GABA is the major inhibitory neurotransmitter in the central nervous system (CNS).
• GABA receptors are composed of five subunits (α, β, and γ) spanning the postsynaptic membrane.
• GABA binding triggers chloride channel opening, allowing chloride ions to enter.
• Influx of chloride ions hyperpolarizes the neuron, decreasing neurotransmission by inhibiting action potential formation.

Therapeutic Uses

• Anxiety disorders: Not for everyday stress, reserved for severe anxiety, short-term use to avoid tolerance and severe withdrawal. Longer-acting agents are preferred over shorter-acting ones.
• Muscular disorders: Useful for muscle spasms (e.g., muscle strain), muscle spasticity in multiple sclerosis and cerebral palsy.
• Seizures: Useful in absence epilepsy and grand mal seizures, acute alcohol withdrawal.
• Sleep disorders: All benzodiazepines have sedative effects but not all are hypnotics; they reduce latency to sleep onset and increase stage 2 non-REM sleep.

Classification of Benzodiazepines

• Long-acting: Diazepam, clonazepam, chlordiazepoxide, clorazepate, flurazepam
• Intermediate-acting: Lorazepam, alprazolam, temazepam
• Short-acting: Triazolam, midazolam, oxazepam

Dependence

• Benzodiazepines can cause psychological and physical dependence, especially with high doses.
• Withdrawal symptoms include confusion, anxiety, agitation, restlessness, insomnia, and tension.

Adverse Effects

• Common: Drowsiness, confusion, ataxia (at high doses).
• Precautions: Avoid in liver disease, acute narrow-angle glaucoma, pregnancy, and breastfeeding. Alcohol and other CNS depressants enhance benzodiazepine effects.

Other Anxiolytics and Hypnotics

• Zolpidem: Not a benzodiazepine but acts on the same receptor; shorter duration, less rebound withdrawal.
• Hydroxyzine: Antihistamine with antiemetic (anti-vomiting) and sedative properties, used before surgery.
• Flumazenil: Benzodiazepine antagonist, rapidly reverses benzodiazepine effects, short half-life, repeated doses may be needed to maintain reversal.

Barbiturates

• Formerly used for sedation/sleep maintenance, but are now largely replaced by benzodiazepines due to concerns about enzyme induction, tolerance, dependence, and narrow safety margin.
• Mechanism of action: interact with GABA receptors, block excitatory glutamate receptors.
• Individual drugs: Thiopental (ultra-short-acting), phenobarbital (long-acting) used in various neurological conditions.
• Non-barbiturate sedatives: Chloral hydrate (pro-drug, converted to trichloroethanol, sedative and hypnotic)

Antihistamines

• e.g., Diphenhydramine.
• Mild sedative properties; used in mild insomnia situations.

Ethanol

• Anti-anxiety and sedative effects but toxic potential outweighs benefits.
• Chronic use can lead to liver disease, gastritis, and nutritional deficiencies; also causes cardiotoxicity.
• Benzodiazepines are the treatment of choice for alcohol withdrawal.

Disulfiram

• Blocks acetaldehyde oxidation, causing unpleasant effects (flushing, tachycardia) upon alcohol ingestion; used to discourage alcohol consumption (aversive therapy).

Buspirone

• Anxiolytic; acts on serotonin receptors, does not have significant dependence issues, suitable for some older adults.

Melatonin

• Secreted by the pineal gland; improves sleep-wake cycle.
• Ramelteon is a melatonin receptor agonist.
• Side effects often involve gastrointestinal issues.

Additional Information (from the last few pages)

• The antidote to diazepam overdose is Flumazenil.
• Disulfiram is used to discourage alcohol consumption.
• Flumazenil is the best agent for benzodiazepine overdose in the emergency room.