Medical Pharmacology Chapter 12:  Anxiolytics and Sedative-Hypnotics

• Advantages and disadvantages of each class relative to the others (Benzodiazepines vs Barbiturates)

  • Benzodiazepines have proven far safer than barbiturates for pharmacological hypnosis and both safer and more effective in management of generalized anxiety disorder.

  •  The use of barbiturates therefore has declined as a result of more favorable pharmacological properties associated with benzodiazepines.

    • Tolerance to barbiturates occurs more often than that observed with benzodiazepines

    • Barbiturate abuse liability is greater than with benzodiazepines.

    • Barbiturate use may be accompanied by significant drug-drug interaction.

    • Barbiturates lack CNS specificity

  • Prominent barbiturate use:

    • Barbiturates are used as therapeutic/diagnostic aids in psychiatry

    • Barbiturates also are effective in  reducing cerebral edema following surgery, head injury or cerebral ischema.

    • Barbiturates are also effective antiepileptic medications

     

• Major drugs and drug classes used to treat anxiety

  • Chlordiazepoxide (Librium), Diazepam (Valium), Oxazepam (Serax), Clorazepate (Tranxene), Lorazepam (Ativan),Alprazolam (Xanax), Halazepam (Paxipam), barbiturates (rarely), buspirone.

    • Diazepam

      Diazepam Clinical Uses Reduce anxiety prior to surgery; may reduce amount of inhalational agent required. Drug of choice by IV for termination of status epilepticus Anxiolytic Reduce anxiety prior to endoscopy and cardioversion Mangement of acute ethanol withdrawal Adverse Effects: Contraindications by injection: shock, coma, acute alcohol intoxication, infants < 30 days old by tabet: children less than 6 months; acute narrow angle glaucoma, untreated open angle glaucoma, during or within 14 days of MAO inhibitor therapy; safe use in pregnancy not established. Cautious Use: Impaired renal or hepatic function Mental depression Drug abuse Addiction prone patients Elderly or in patients with COPD (I.V) Side Effects (Partial Listing): CNS: drowsiness, fatigure, amnesia CV: hypotension, cardiovascular collapse Eye: Blurred vision GI: dry mouth, nausea, constipation GU: gynecomastia (prolonged use), incontinence, urinary retention Shannon, M.T., Wilson, B.A., Stang, C. L. In, Govoni and Hayes 8th Edition: Drugs and Nursing Implications Appleton & Lange, 1995, pp 396-397.

    • Benzodiazepines are commonly used for management of generalized anxiety disorder.

      • Most, but not all, clinical research studies have shown that benzodiazepines are more effective than placebo in treating anxiety.

    • Factors that have promoted the popularity of these drugs include:

      •  Safety

      •  Pharmacology

      •  Patient demand.

    • Benzodiazepines may be more efficacious and certainly safer in management of anxiety compared to barbiturates.

      • Barbiturates and non-barbiturates such as meprobamate have been used in the past to manage anxiety.

        • However, these drugs are now rarely used.

      • Barbiturates are also infrequently used for this indication because of:

        • Excessive sedation/intoxication at anxiolytic dosages

        • Tolerance

        • Physical dependence

        • Potentially life-threatening withdrawal reactions

        • Life-threatening toxicity with overdosage.

  • Buspirone

    • Buspirone,which has selective affinity of 5-HT_1A, is a relatively new anxiolytic.

    • Buspirone seems most effective in mild anxiety and is not effective compared to benzodiazepines and certain antidepressant agents in treatment of panic disorder.

    • Buspirone does not exhibit cross-tolerance with benzodiazepines or other sedative-hypnotics.

Baldessarini, R. J., Drugs and the Treatment of Psychiatric Disorders, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp. 421-427.

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