Anxiolytic Drugs Flashcards
What are anxiolytic drugs?
Drugs that reduce anxiety
Classificaton of anxiolytic drugs.
●Benzodiazepine derivatives:
▪︎short-acting
(duration of the action is 1-6 hours): triazolam.
▪︎intermediate-acting
(duration of the action is 6-24 hours): oxazepam,
lorazepam,
alprazolam;
▪︎long-acting
(duration of the action is more than 24 hours):
diazepam,
chlordiazepoxide,
medazepam,
nitrazepam,
●agonists of serotonin 5-HT₁A receptors:
buspirone
The mechanism of action. (Anxiolytic Drugs)
●The mechanism of the action of benzodiazepines is the interaction with
the GABA receptors leading to the potentiation of inhibitory effects of GABA.
●The GABA receptors belong to the family of the receptors linked to ligand-gated ion channels.
●Binding of GABA to the receptor contributes to the opening of CI channels.
●Benzodiazepines bind with the GABA receptor, but at the site different from the binding site of GABA
(allosteric interaction).
●Every receptor consists of five subunits.
●There are 16 possible subunits of the GABA receptors:
six a,
three ß, three y, 8, ε, 0, л. (correct symbols in the textbook)
●For anxiolytic properties of benzodiazepines interaction with the GABA receptors containing alpha-2 and/or alpha-3 subunits is necessary.
●The binding site for GABA is located between alpha-1 and beta-2 subunits.
●Benzodiazepines bind between alpha and gamma subunits.
●For anxiolytic properties of benzodiazepines interaction with the GABA receptors containing alpha-2 and/or alpha-3 subunits is required.
●The hypnotic drug zolpidem and the
antagonist of benzodiazepine flumazenil bind to the same site as benzodiazepines.
●Barbiturates bind to some types of alpha and beta subunits causing the increase of duration of the opening of the Cl channels.
Pharmacokinetics properties of anxiolytic drugs.
●All benzodiazepine derivatives are easily absorbed from the gastrointestinal tract and can be administered orally.
●Triazolam and diazepam
are absorbed more rapidly than other benzodiazepines.
Elimination of the benzodiazepine anxiolytics?
●Includetwo phases of biotransformation:
■phase I of biotransformation - cytochrome P450-dependent microsomal oxidation with the generation of active metabolites.
■phase II of biotransformation - conjugation with glucuronic acid
(inactive metabolites are formed).
■Then the metabolites of benzodiazepines are excreted with the urine.
Metabolism of
oxazepam and lorazepam includes only phase II, so the duration of their effect is relatively shorter than for the most of other drugs of this group.
●Triazolam & alprazolam have relatively short living metabolites of phase 1
So the duration of their effect is also relatively short.
The main pharmacological effects of the benzodiazepine anxiolytics?
●anxiolytic effect (decrease of anxiety).
●sedative and hypnotic effects.
●anticonvulsant effect
(inhibition of convulsions or seizures).
●skeletal muscle relaxation.
Adverse effects of the benzodiazepine anxiolytics?
●the drug dependence
(in therapeutic doses there is psychological dependence, but regular use of higher doses can lead to the formation of the physiological dependence)
●the symptoms of sedative and muscle relaxant effect
(drowsiness,
impaired memory,
attention,
psychomotor reaction).
Application of benzodiazepine anxiolytics.
●anxiety disorders.
● insomnia
(triazolam and nitrazepam are mainly used as hypnotic drugs)
●anesthetic premedication (benzodiazepines relieve anxiety before the operation and also potentiate the effect of anesthetics)
●seizure disorders
(diazepam intravenously is the drug of choice in seizures of unknown etiology)
●spasticity of skeletal muscles.
●alcohol withdrawal syndrome (long-acting drugs, mainly chlordiazepoxide are used;
they relieve such symptoms of alcohol withdrawal syndrome as anxiety and convulsions).
Distinctive features of buspirone.
• slow development of the anxiolytic effect.
• very weak sedative properties, lack of the hypnotic effect.
lack of the muscle relaxant effect.
• does not induce drug dependence.
