SEDATIVE AND HYPNOTIC DRUGS

Anxiolytic drugs are used to treat the symptoms of anxiety, where as hypnotic drugs used to treat insomnia. The same drugs are used for both purposes.

Classes of anxiolytic and hypnotic drugs: The main groups of the drugs are:

1. Benzodiazepines. Benzodiazepines are the most important group, used as sedative and hypnotic agents.
2. 5- HT_1A receptor agonist (e.g. buspirone). It is recently introduced anxiolytic.
3. Barbiturates (phenobarbitone). They are nowadays less commonly used as sedative- hypnotics.
4. b -adrenoceptor antagonists (e.g. propranolol). They are used to treat some forms of anxiety, where physical symptoms (sweating, tremor, and tachycardia), are troublesome. They are not used as hypnotics.
5. Miscellaneous drugs (chloral hydrate, paraldehyde, and diphenhydramine). These drugs are not commonly recommended for axiety or insomia.

Benzodiazepines

Benzodiazepines are well absorbed when given orally. They bind strongly to plasma proteins, however, many of them accumulate gradually in the body fat (i.e. they are highly lipid soluble). Benzodiazepines are inactivated by the liver and excreted in the urine.

Based on their duration of action roughly divided into short acting (flurazepam, triazolam), medium acting (alprazepam, lorazepam) and long acting compounds (diazepam, chlordiazepoxide, clonazepam).

Pharmacodynamics

Act by binding to a specific regulatory site on the GABA_A receptor, thus enhancing the inhibitory effects of GABA. Central nervous system effects of benzodiazepines include:

1. Reduction of anxiety and aggression.
2. Sedation and induction of sleep.
3. Reduction of muscle tone and coordination.
4. Anticonvulsant effects.

Clinical Uses

• Treatment insomnia
• Anxiety
• Preoperative mediations
• Acute alcohol withdrawal
• As anticonvulsants
• Chronic muscle spasm and spasticity

Unwanted effects

• Toxic effects due to acute overdosage causes prolonged sleep.
• Unwanted effects occurring during normal therapeutic use includes: drowsiness, confusion, amnesia, and impaired motor coordination.
• Tolerance and dependance: Pharmacokinetic and tissue tolerance and also cause physical dependance. i.e. stopping benzodiazepines treatment after weeks or months causes an increase in symptoms of anxiety.

5 – HT_1A receptor agonist

Buspirone is a potent agonist of. 5 – HT_1A receptors. Anxiolytic effects take days to weeks to develop. Buspirone does not cause sedation, motor incoordiation and withdrawal effects. The main side effects are nausea, dizziness, headache, and restlessness.

Barbiturates

They are non-selective CNS depressants, which produce effects ranging from sedation and reduction of anxiety, to unconsciousness and death from respiratory and cardiovascular failure.

Barbiturates act by enhancing action of GABA, but less specific than benzodiazepines. They are potent inducers of hepatic drug metabolizing enzymes, hence likely to cause drug interaction. Tolerance and dependance occur, more than benzodiazepines.