Anxiolytic and hypnotic drugs

overview Anxiety is an unpleasant state Disorders involving anxiety are the most common mental disturbances Function clinically as both anxiolytic and hypnotic (sleep-inducing) agents.

benzodiazepines The most widely used anxiolytic drugs More effective and safer than barbiturates and meprobamate

Mode of action Binding of -aminobutyric acid to its receptor Triggers an opening of a chloride channel Causes a small hyperpolarization that moves the postsynaptic potential away

Actions Reduction of anxiety: at low doses, the benzodiazepines are anxiolytic. Sedative and hypnotic actions: Anticonvulsant: Muscle relaxant:

Therapeutic uses Anxiety disorders: in treating the anxiety that accompanies some forms of depression and schizophrenia.

Therapeutic uses Muscular disorder: in the treatment of skeletal muscle spasms. Spasticity such as multiple sclerosis and cerebral palsy.

Therapeutic uses Seizures: clonazepam is useful in the chronic treatment of epilepsy, whereas diazepam is the drug of choice in terminating grand mal epileptic seizures and status epilepticus.

Therapeutic uses Sleep disorders: flurazepam: reduces both sleep-induction time and the number of awakenings, and increases the duration of sleep. Temazepam: is useful in patients who experience frequent wakening Triazolam: used to induce sleep in patients with recurring insomnia.

Pharmacokinetics Absorption and distribution: lipophilic, rapidly and completely absorbed after oral administration Duration of actions Fate: metabolized by the hepatic microsomal metabolizing system and are excreted in urine

Dependence Psychological and physical dependence on benzodiazepines can develop Withdrawal symptoms: including confusion, anxiety, agitation, restlessness, insomnia, and tension.

Adverse effects Drowsiness and confusion: ataxia occurs at high doses Cognitive impairment Precautions: They potentiate alcohol and other CNS depressants.

barbiturates Mode of actions: interfere with sodium and potassium transport across cell membranes. This leads to inhibition of mesencephalic reticular activating system.

Actions Depression of CNS: at low doses, the barbiturates produce sedation. At higher doses, the drugs cause hyponsis, followed by anesthesia

Actions Respiratory depression: suppress the hypoxic and chemoreceptor response to CO2 Enzyme induction: barbiturates induce P-450 microsomal enzymes in the liver

Therapeutic uses Anesthesia: thiopental are used intravenously to induce anesthesia Anticonvulsant: phenobarbital is used in long-term management of tonic-clonic seizures, status epilepticus, and eclampsia Anxiety: mild sedatives to relieve anxiety, et.al Most have been replaced by the benzodiazepines

Pharmacokinetics Absorbed orally and distributed widely throughout the body

Adverse effects CNS: drowsiness, impaired concentration, and mental and physical sluggishness. Drug hangover: produce a feeling of tiredness well after the patient awakes. Precautions: increase porphyrin synthesis. Addiction: abrupt withdrawal may cause tremors, anxiety, weakness, seizures. et.al.