Katzung 12th ed - Chapter 22 - Sedative-Hypnotic Drugs (1) Flashcards
What is the basic chemical structure of most benzodiazepines?
3 rings (2 hexacarbon rings and one ring that contains two N atoms in place of C), and a side group.
What is important about sedative-hypnotic drugs and pregnancy?
All sedative-hypnotic drugs cross the placental barrier.
What is the method of clearance for all benzodiazepines?
Hepatic metabolism, Renal excretion.
What is important about the metabolites produced by phase I reactions of diazepam?
These phase I metabolites are pharmacologically active, with a long half-life of 24-48hrs. These include desmethyldiazepam, oxazepam and temazepam.
What is important about the dose-response curve of barbiturates? How is this thought to be different for benzodiazepines and other newer drugs?
Barbiturates have lethal cumulative effects, because the dose-response curve increases linearly. In contrast, newer agents have a plateau effect after the dose surpasses a certain level.
What is the basic effect of GABA-A receptor activation at the molecular level?
The GABA-A receptor functions as a chloride ion channel. Activation results in chloride ion passage into the cell, which hyperpolarizes the membrane.
Benzodiazepines and Flumazenil bind to: GABA-A or GABA-B receptors?
GABA-A. (very low affinity for GABA-B).
Do benzodiazepines bind to GABA receptors at the same site as GABA does? How do benzodiazepines affect the GABA receptor?
Benzodiazepines bind to the alpha-subunit of the GABA receptor, whereas GABA binds to the beta-subunit. Benzodiazepines thereby exert their effects allosterically. They do not directly cause the chloride ion channel to open. Rather, they enhance the ability of GABA to cause opening of the channel, with increased frequency of opening.
Name four major clinical effects of sedative-hypnotic drugs.
Sedation (anxiolysis), Hypnosis, Anticonvulsant effects, Muscle relaxation.
What is the approximate half-life of flumazenil after IV administration? How is it cleared?
Half life is approximately 1 hour, due to rapid hepatic clearance.
