Anxiolytiques Flashcards
What are the main therapeutic uses of Benzodiazepines (BZD)?
Anxiolytic, hypnotic, sedative, amnestic, myorelaxant, and anti-convulsant properties.
What is the mechanism of action of BZD?
They enhance GABAergic transmission by binding to BZD receptors, increasing the probability of chloride channel opening in the presence of GABA.
What are the risks associated with repeated BZD administration?
Toxicomanogenic potential, tolerance, psychic and physical dependence, and withdrawal syndrome upon abrupt cessation or dose reduction.
How do BZDs compare to carbamates regarding mechanism?
BZDs increase the probability of GABA-mediated chloride channel opening, while carbamates also modulate GABA receptors but additionally block polysynaptic reflexes.
How are BZDs absorbed?
Complete digestive absorption (variable speed), variable rectal absorption, slower IM absorption, rapid and complete IV absorption.
How are BZDs distributed in the body?
High plasma protein binding, high tissue distribution (VD > 1 L/Kg), cross the blood-brain barrier (BBB) and placenta, stored in fat tissue with chronic use.
Describe the metabolism of BZDs.
Primarily hepatic via desalkylation, hydroxylation, and conjugation (mainly glucuronidation). Primary metabolites can be active, while conjugated metabolites are inactive.
How are BZDs eliminated?
Mainly renal excretion as conjugated metabolites (<1% unchanged). Variable elimination half-lives. Some biliary excretion and passage into breast milk.
What is a key metabolic pathway for Diazepam and Prazepam leading to Oxazepam?
Both can be metabolized via Nordiazepam (long half-life) which is then hydroxylated to Oxazepam before glucuronidation.
What are the main symptoms of acute BZD intoxication?
CNS depression (ataxia, drowsiness, calm coma), rarely significant respiratory depression or cardiovascular issues, hypothermia. Initial agitation/disinhibition possible.
What are potential issues with chronic BZD intoxication?
Impaired performance, vigilance/concentration issues, anterograde amnesia, confusion/hypotonia (elderly), depression, paradoxical effects (excitation, anxiety).
What is the general approach to treating acute BZD intoxication?
Primarily symptomatic: airway management, cardiovascular/neurological monitoring, hydration.
What evacuation method can be used for BZD overdose?
Early administration of activated charcoal. Gastric lavage only for recent massive ingestion with significant symptoms.
What is the specific antidote for BZD overdose, and how does it work?
Flumazenil. It is a competitive antagonist at the BZD receptor site.
What are examples of BZD-like compounds (Z-drugs)?
Zopiclone, Zolpidem.
How do Z-drugs compare pharmacodynamically to BZDs?
Similar effects (hypnotic, sedative, etc.) by acting as agonists on GABA-omega receptors, modulating the chloride channel, despite structural differences.
Do Z-drugs carry risks similar to BZDs?
Yes, prolonged use can lead to dependence and withdrawal syndrome.
How is intoxication with Z-drugs treated?
Similar to BZD intoxication, including the use of Flumazenil.
How does the acute toxicity of carbamates (e.g., Meprobamate) compare to BZDs?
Carbamates have significantly higher acute toxicity than BZDs.
What is a key characteristic of Meprobamate regarding drug metabolism?
Meprobamate is a potent enzyme inducer.
What phenomenon can occur with massive ingestion of Meprobamate, affecting absorption?
Formation of gastric conglomerates, slowing absorption and potentially causing triphasic coma.
What is the mechanism of action for Meprobamate?
Modulates GABA receptors and blocks polysynaptic spinal reflexes.
Describe the typical presentation of acute Meprobamate intoxication.
Triphasic CNS depression (coma), respiratory depression, dose-dependent cardiovascular collapse.
What specific treatment considerations exist for Meprobamate overdose?
Gastric lavage effective up to 12h (consider gastroscopy for conglomerates), activated charcoal, extracorporeal elimination in severe cases.
