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ANXIOLYTIC AND HYPNOTIC DRUGS.

SEDATIVES,HYPNOTICS(BENZODIAZEPINES,BARBITURATES),ALCOHOL.

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Lecture Objective

Anxiolytic and Hypnotic drugs.

  • BENZODIAZEPINES
    • Alprazolam - Triazolam - Flurazepam
    • Chlordiazepoxide - Diazepam - Lorazepam
    • Clonazepam - Estazolam - Quazepam
    • Clorazepate - Oxazepam - Temazepam

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  • BENZODIAZEPINE ANTAGONIST
    • Flumazenil
  • OTHER ANXIOLYTIC DRUGS.
    • Buspirone
    • Hydroxyzine
    • Antidepressants

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  • BARBITURATES
    • Amobarbital
    • Phenobarbital
    • Pentobarbital
    • Secobarbital
    • Thiopental
  • OTHER HYPNOTIC AGENTS
    • Antihistamines
    • Chloral hydrate
    • Ethanol
    • Zaleplon
    • Zolpidem

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Definition of Anxiety.

  • An unpleasant state of tension, apprehension or uneasiness arising from an unknown source.

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Physical symptoms.

  • Tachycardia
  • Sweating
  • Trembling
  • Palpitations

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BENZODIAZEPINES

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Classification of Benzodiazepines.

Long-acting.

  • Clorazepate
  • Chlordiazepoxide
  • Diazepam.
  • Flurazepam
  • Quazepam.

Intermediate-acting.

  • Alprazolam
  • Estazolam
  • Lorazepam
  • Temazepam.

Short-acting.

  • Triazolam.
  • Oxazepam.

Duration of action 1- 3 days

Duration of action 10 – 20 hrs.

Duration of action 3 – 8 hrs.

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Mechanism of action.

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Actions of Benzodiazepines.

  • Reduction of anxiety
  • Sedative and hypnotic actions
  • Anterograde amnesia
  • Anticonvulsant
  • Muscle relaxant

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Therapeutic uses.

  • Anxiety disorders.
    • Panic disorders.
    • GAD
    • SAD
    • Post traumatic stress disorders
    • COD

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  • Muscular disorders.
    • Skeletal muscle spasms
    • Spasticity from degenerative disorders e.g. cerebral palsy.
  • Amnesia
    • Midazolam – injectable BZ for induction of anesthesia
  • Seizures
    • Clonazepam (epilepsy)
    • Diazepam
    • Lorazepam.
    • Chlordiazepoxide, Clorazepate (alcohol withdrawal and alcohol related seizures)
  • Sleep disorders.
    • Flurazepam
    • Temazepam
    • Triazolam

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Pharmacokinetics.

  • Good oral bioavailability
  • Lipophilic
  • Metabolized by hepatic microsomal system.
  • Excreted in the urine as glucuronides
  • Crosses placental barrier.

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Dependence.

  • Physical and psychological dependence.

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Adverse effects.

  • Drowsiness and confusion.

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  • Ataxia
  • Cognitive impairment

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Contraindications.

  • Hepatic dysfunction.
  • Narrow angle glaucoma.

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BENZODIAZEPINE ANTAGONIST.

Flumazenil.

  • GABA receptor antagonist.
  • i.v use only.

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Other anxiolytic agents/non benzodiazepines.

  • Buspirone.
  • Hydroxyzine
  • Antidepressants

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BARBITURATES.

Introduction.

  • Mainstay of treatment to sedate or induce and maintain sleep.
  • Cause tolerance, dependence, withdrawal symptoms.
  • Coma in toxic doses.

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Mechanism of action.

  • Interaction with GABA receptors, which enhances GABAergic transmission.
  • Barbiturates potentiate GABA action on chloride entry into the neuron.
  • Barbiturates also can block excitatory glutamate receptors.
  • Barbiturates also can block high-frequency sodium channels.
  • All of these molecular actions lead to decreased neuronal activity.

Actions of barbiturates.

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Actions of barbiturates.

  • Depression of CNS.
  • Respiratory depression.
  • Enzyme induction.

Therapeutic uses.

  • Anesthesia.
    • Thiopental
  • Anticonvulsant.
    • Tonic-clonic seizures.
    • Status epilepticus.
    • Eclampsia.
    • Recurrent febrile seizures.
    • Phenobarbital
  • Anxiety.

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Pharmacokinetics.

  • Good oral bioavailability.
  • Wide redistribution.
  • Cross the placental barrier.
  • Metabolized in the liver
  • Excreted in the urine.

Adverse effects.

  • CNS
  • Drug hangover
  • Precautions.
    • Induce P450 system
    • Porphyria.
  • Physical dependence
  • Poisoning.

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OTHER HYPNOTIC AGENTS.

Ethanol.

  • Ethanol (ethyl alcohol) has anxiolytic and sedative effects.

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  • Its toxic potential outweighs its benefits.

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  • It is a CNS depressant, producing sedation and hypnosis with increasing dosage.

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  • Ethanol has a shallow dose-response curve, thus sedation occurs over a wide dosage range.

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  • It has a volume of distribution close to that of total body water.

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  • Ethanol is metabolized primarily in the liver, first to acetaldehyde by alcohol dehydrogenase then to acetate by aldehyde dehydrogenase.

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  • Elimination is mostly through the kidney, but a fraction is excreted through the lungs.

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Disulfiram.

  • This blocks the oxidation of acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase.

Naltrexone.

  • This is a long acting opiate antagonist.

Acamprosate.

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