Sedative-Hypnotics: Barbiturates and Benzodiazepines Lecture Notes

Vocabulary flashcards covering the pharmacological properties, medical uses, and mechanisms of action of sedative-hypnotics including barbiturates, benzodiazepines, and GHB.

Sedative-hypnotics

A diverse group of compounds that depress the Central Nervous System (CNS) and behavior, including alcohol, barbiturates, and benzodiazepines.

Barbituric acid

The foundation of all barbiturates, first synthesized by von Baeyer in 1864.

Barbital (1903)

The first barbiturate drug to be marketed.

Lipid solubility

A pharmacokinetic factor where high levels allow barbiturates to reach the brain quickly, but also lead to brief durations due to redistribution to body fat stores.

Ultra-short-acting barbiturates

Barbiturates like Thiopental (Pentothal) with high lipid solubility, an onset of $10-20\,s$, and a duration of $20-30\,min$ used for intravenous anesthesia.

Long-acting barbiturates

Barbiturates like Phenobarbital (Luminal) with low lipid solubility and a duration of $10-12\,h$ used for prolonged sedation and seizure control.

Slow-wave sleep

Deep sleep that is reduced along with REM sleep by chronic use of barbiturates.

Benzodiazepines (BZs)

Anxiolytics like Valium and Librium that progressively replaced barbiturates for treating anxiety, insomnia, and alcohol withdrawal due to their higher safety margin.

Therapeutic Index

The ratio calculated as $\text{LD}<em>{50} / \text{ED}</em>{50}$ used to measure drug safety; it is much higher for benzodiazepines than for barbiturates.

Flunitrazepam (Rohypnol)

A rapid-onset benzodiazepine sometimes used in date rape cases.

GHB (gamma-hydroxybutyrate)

A GABA analog and popular "club drug" that acts as a low-affinity agonist of $GABA_B$ receptors and occurs naturally in the brain in small quantities.

GABA (gamma-aminobutyric acid)

The most important inhibitory neurotransmitter in the adult, vertebrate brain, synthesized from glutamate.

vGAT

The vesicular GABA (and glycine) transporter used in GABA transmission.

GAT-1, 2, 3

Membrane GABA transporters located on both neurons and glia.

GABAA Receptors

Ionotropic ligand-gated chloride ($Cl^-$) channels consisting of 5 subunits (usually $2\alpha$, $2\beta$, and a $\gamma$ or $\delta$).

GABAB Receptors

Metabotropic G-protein-coupled receptors for GABA.

Muscimol

A specific agonist for $GABA_A$ receptors.

Bicuculline

A specific antagonist for $GABA_A$ receptors.

Allosteric modulators

Drugs like BZs and barbiturates that do not bind to the same site as GABA but enhance the ability of GABA to cause chloride influx through the receptor.

Diazepam effect on GABAA

Causes $GABA_A$ channels to open more frequently in the presence of GABA.

Phenobarbital effect on GABAA

Causes $GABA_A$ channels to stay open for longer durations in the presence of GABA.

$\alpha 1$-containing receptors

Subtypes of $GABA_A$ receptors required for the sedative and amnesic effects of benzodiazepines.

$\alpha 2$-containing receptors

Subtypes of $GABA_A$ receptors required for the anxiolytic effects of benzodiazepines.

Disinhibition

The process by which benzodiazepines increase the activity of dopaminergic neurons by inhibiting GABAergic interneurons.