CNS Depressants/Antianxiety Agents

1. CNS depressants

   1. Barbiturates

      1. Classification according to their rate of onset and duration of action

         1. Ultrashort-acting barbiturates

            1. Thiopental

            2. Thiamylal

         2. Short- to intermediate-acting barbiturates

            1. Secobarbital

            2. Pentobarbital

         3. Long-acting barbiturates

            1. Phenobarbital

      2. Pharmacokinetics

         1. Rate of distribution depends on their lipid solubility.

         2. Metabolism can be altered by induction of hepatic enzymes.

      3. Mechanism of action

         1. Bind to a specific site on GABA_A receptors

         2. Facilitate the actions of GABA

         3. Can activate the GABA_A receptor directly at large concentrations

      4. Clinical uses

         1. Induction of anesthesia

         2. Treatment of some forms of epilepsy

      5. Adverse effects

         1. CNS depression (i.e., sedation)

         2. Respiratory depression

         3. Tolerance

         4. Dependence

         5. Abuse

      6. Drug interactions

         1. Additive effects with other CNS depressants

         2. Induction of hepatic enzymes can accelerate metabolism of other drugs.

   2. Benzodiazepines

      1. Classification according to their rate of onset and duration of action

         1. Short-acting

            1. Midazolam

1. Intermediate-acting

   1. Lorazepam

   2. Oxazepam

   3. Temazepam

   4. Alprazolam

   5. Triazolam

2. Long-acting

   1. Flurazepam

   2. Diazepam

   3. Clonazepam

   4. Chlordiazepoxide

1. Pharmacokinetics

   1. Metabolism can result in the formation of active metabolites.

2. Mechanism of action

   1. Bind to a specific site on the GABA_A receptor

   2. Facilitate the actions of GABA

   3. Do NOT activate the GABA_A receptor directly

3. Clinical uses

   1. Anxiolytic effects

   2. Sedative effects

   3. Muscle relaxant effects

   4. Anticonvulsant effects

   5. Induction of anesthesia

4. Adverse effects

   1. CNS depression (i.e., sedation)

   2. Anterograde amnesia

   3. Respiratory depression

   4. Tolerance

   5. Dependence

   6. Abuse potential

5. Drug interactions

   1. Additive effects with other CNS depressants

2. Anxiety

   1. Types of anxiety disorders

      1. Generalized anxiety disorder—persistent state of heightened anxiety with increased levels of motor tension and autonomic hyperactivity

      2. Panic disorder—recurrent, discrete periods of sudden and intense fear or discomfort accompanied by autonomic arousal

   2. Treatment of anxiety disorders

      1. Benzodiazepines

         1. Immediate anxiolytic effects

         2. Alprazolam—only benzodiazepine marketed for panic disorder

      2. Buspirone

         1. Serotonin agonist

         2. Long latency to obtain anxiolytic effects

         3. Not effective in treating panic disorder

         4. Adverse effects include headache, dizziness and nausea

      3. Antidepressants—first choice for treatment of panic disorder

         1. SSRIs

         2. Tricyclic antidepressants

         3. MAO inhibitors

      4. Beta blockers—used to prevent performance anxiety

3. Insomnia

   1. Causes of insomnia

      1. Stress or emotional upset

      2. Aging

      3. Medical and psychiatric illness

      4. Drugs/Alcohol

      5. Sleep cycle disruption (jet lag)

2. Treatment of insomnia

   1. Benzodiazepines

      1. Triazolam

      2. Flurazepam

      3. Temazepam

      4. Zolpidem

      5. Zaleplon

   2. Antidepressants

   3. Antihistamines

Category: Pharmacology Notes