2020 lecture 20

Lecture 20: Sedative Hypnotics in Psychology 20

Introduction to Sedative Hypnotics

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

    • Treatment of anxiety (anxiolytics)

    • Treatment of insomnia (difficulty falling asleep and staying asleep)

  • Although their usage for insomnia is diminished compared to the past, they are still used occasionally for controlling epilepsy due to their ability to suppress neuronal excitability.

  • Significant recreational use of these drugs exists.

The Role of Anxiety in Society

  • A substantial proportion of the population experiences some form of anxiety, necessitating the availability of drugs for treatment.

    • Anxiety is a condition experienced throughout human history.

  • Alcohol was one of the earliest substances used to alleviate anxiety:

    • While alcohol has anxiolytic properties, it has undesirable side effects, including:

    • Behavioral impairment

    • Strong physical dependence and withdrawal symptoms.

Historical Context of Sedative Hypnotics

  • Discussion of early sedative hypnotics:

    • Chloral hydrate was first synthesized in the early 1800s and was commonly used through the 1800s.

    • Chloral hydrate is associated with addiction, as documented in the Quarterly Journal of Inebriety.

  • Chloral hydrate was used as "knockout drops" or "Mickey Finn":

    • These terms refer to administering chloral hydrate covertly in drinks to incapacitate someone for exploitative purposes.

    • Such practices of administering incapacitating drugs for sexual exploitation are historically long-standing.

Development of Anxiolytics: Barbiturates and Benzodiazepines

  • Barbiturates:

    • Historically the first class of anxiolytics, synthesized from barbituric acid created by Adolphe von Baeyer in 1864.

    • Barbituric acid:

    • Parent compound synthesized by combining malonic acid (from apples) with urea (found in urine).

    • Diethylbarbituric acid was the first modification and effective barbiturate, marketed as Barbitol (trade name Veranol).

    • Variations in barbiturates created different effects based on duration and onset:

    • Long Acting: Phenobarbital (onset ~1 hour, duration ~6 hours)

    • Intermediate Acting: Amobarbital (blue pills/capsules, trade name Amitol)

    • Short Acting: Pentobarbital (generic Nimbutal, yellow capsules, street names include "yellow jackets")

    • Ultra Short Acting: Use in presurgical anesthetics, involved drugs include hexobarbital and thiopental.

Classification of Barbiturates

  • Classification based on onset and duration of effects:

    • Long Acting (Phenobarbital): Onset ~1 hour, duration ~6 hours.

    • Intermediate Acting (Amobarbital): Commonly referred to as "blue pills" or "blue angels".

    • Short Acting (Pentobarbital): Yellow capsules; street names include "yellow jackets" and "abbots".

    • Ultra Short Acting: Used for induction of anesthesia; includes drugs like Propofol, associated with cases of abuse and celebrity deaths.

Neurochemical Mechanisms of Action

  • Barbiturates exert their effects via the GABA neurotransmitter system:

    • GABA (inhibitory neurotransmitter) binds to its receptor, promoting neuronal inhibition.

    • Barbiturates add to GABA's effects by binding to a secondary site on the GABA receptor, increasing ion channel opening duration and further inhibiting neuronal activity.

  • They also interfere with glutamate transmission, contributing to amnestic effects (memory loss).

Effects and Risks of Barbiturates

  • Effects include:

    • Sedation and relaxation

    • Reduced anxiety

    • Amnesia at higher doses

    • Possible dependence and withdrawal effects, including the potential for overdose.

    • Low therapeutic index indicates a narrow margin between therapeutic and lethal doses, increasing overdose risk.

Development of Tolerance and Physical Dependence

  • Barbiturates show clear signs of tolerance, particularly to reinforcing effects, not necessarily lethal ones:

    • Cross-tolerance with alcohol occurs, leading to reduced effects of either drug when taken together due to similar neurobiological pathways.

    • Withdrawal symptoms can be severe and mirror those of alcohol withdrawal, including convulsions and delirium tremens (DTs).

Alternative Sedative Hypnotics: Mefenacin and Meprobamate

  • Mefenacin carbonate developed accidentally while researching antibacterial compounds:

    • Not effective as an antibacterial but noted for its calming properties.

    • Later modified to create meprobamate (trade names Milltown and Equanil), which became popular as an anxiolytic and sedative, though it also produced physical dependence and withdrawal symptoms.

  • Meprobamate:

    • Phrase "tranquilizer" first used with this drug in a medical context.

Methaqualone (Quaalude)

  • Originally developed as an antimalarial but found to have sedative effects:

    • Became widely used both recreationally and in medicine during the 1960s.

    • Street names include "disco biscuits" and "ludes".

  • Presence in popular culture and involvement in notable drug-related deaths, notably associated with sexual assaults in recent history.

Conclusion

  • Examined sedative hypnotics, their historical context, levels of medical use versus recreational abuse, and detailing of specific drugs including barbiturates, meprobamate, and methaqualone.

  • Transition toward examining the next class of anxiolytics, benzodiazepines, in upcoming lectures.