Psychology 20 - Sedative Hypnotics Lecture Notes

Sedative Hypnotics Overview

  • Sedative hypnotics are a class of drugs primarily used for:

    • Treatment of anxiety (anxiolytics).

    • Managing insomnia (historically more common).

    • Controlling epilepsy by suppressing neuronal excitability.

Historical Context

  • High prevalence of anxiety in the population has led to a need for anxiolytic drugs.

  • Alcohol was one of the earliest substances used to reduce anxiety.

    • Alcohol is not a suitable anxiolytic due to significant side effects, including:

    • Behavioral impairment

    • Strong physical dependence and withdrawal symptoms.

  • Early sedative hypnotics include chloral hydrate, synthesized in the early 1800s.

    • First extensively used, now associated with recreational abuse and physical dependence.

    • Historical references include:

    • "Quarterly Journal of Inebriety"

    • Usage as "knockout drops" or Mickey Finn, leading to inappropriate drugging.

Drug Classes

  • Two main classes of anxiolytics and sedatives:

    1. Barbiturates

    • Oldest class

    • Parent compound synthesized by Adolphe von Baeyer in 1864 through:

      • Combining malonic acid (found in apples) with urea (found in urine).

    • Initial compound: barbituric acid, not effective until modified.

    • First effective barbiturate: Diethylbarbituric acid (trade name: Veranol).

      • Derived from barbituric acid with two diethyl groups added.

      • Named after the peaceful city of Verona.

    1. Benzodiazepines

    • Emerged in the 1960s.

Classification of Barbiturates

  • Classified into categories based on onset and duration of action:

    • Long-acting: e.g., Phenobarbital

      • Onset in about 1 hour, duration ~6 hours.

    • Intermediate-acting: e.g., Amobarbital (trade name Amitol)

      • Onset ~30 minutes, duration ~6 hours.

      • Street names include blue angels, blue dolls.

      • Historically used as a truth serum, but does not guarantee truthful responses.

    • Short-acting: e.g., Pentobarbital (trade name Nimbutal)

      • Commonly abused; known street names include yellow jackets.

    • Ultra short-acting: e.g., Thiopental and Hexobarbital.

      • Used as presurgical anesthetics. Not commonly abused except for propofol (Milk of Amnesia, involved in high-profile cases like Michael Jackson's death).

Effects and Risks of Barbiturates

  • All barbiturates produce:

    • Sedation

    • Anxiety reduction

    • Reduced euphoria at lower doses

    • Interference with REM sleep and potential for REM rebound after discontinuation.

  • Risks include:

    • Low therapeutic index (risk of overdose and death).

    • Severe withdrawal symptoms similar to alcohol:

    • Increased neuronal excitability leading to convulsions and seizures.

  • Alcohol and barbiturates act synergistically, heightening the risk of fatal reactions.

Neurochemical Mechanism

  • Barbiturates enhance GABAergic activity (GABA is an inhibitory neurotransmitter):

    • Occupy a satellite receptor site on the GABA receptor, prolonging the opening of ion channels.

    • Reduce glutamate transmission (excitatory neurotransmitter), causing profound amnesia.

Development of Tolerance and Dependence

  • Tolerance develops rapidly to the reinforcing effects of barbiturates relative to lethal effects, closing the gap between effective and lethal doses:

    • Cross-tolerance with alcohol exists.

  • Withdrawal symptoms mirror the drug effects and can lead to severe complications without medical supervision.

Other Anxiolytic Options Developed

  • Other drugs developed for anxiety treatment in the past during barbiturate popularity included:

    • Mefenacin Carbonate (not effective as an antibacterial but noted for calming effects).

    • Meprobamate (trade names Milltown, Equanil) - marketed as a tranquilizer in 1955:

    • Similar issue with physical dependence as barbiturates but remains in use for anxiety treatment today.

    • Methaqualone (trade name Quaalude): originally an antimalarial, became popular for its calming effects, linked to significant abuse and notable deaths (including Jimi Hendrix, Elvis Presley).

Conclusion

  • The barbiturates had their peak use in the 1950s and 60s but declined due to the introduction of benzodiazepines, which had a better safety profile.

  • Sedative hypnotics continue to be problematic due to their potential for dependence, abuse, and dangerous interactions with other substances (especially alcohol).

  • The lecture affirms the importance of understanding both historical implications and current medical practices surrounding these medications.