Benzodiazepines Flashcards
Meprobamate (MPB)
MPB was an early non-barbiturate anxiolytic
MPB potentiates GABAA and acts as
a weak
partial agonist at the GABA site
Meprobamate (MPB) Eventually withdrawn due to
abuse potential and
narrow safety margin
Chlordiazepoxide found to have
sedative,
anxiolytic, and anticonvulsant effects
(Valium)
diazepam
BZD Effects
Anxiolytic and anticonvulsant
BZD Effects - sedation
less potent than barbiturates
BZD & muscles
Muscle relaxant
BZD Not effective as _____ but
anaesthetics BUT can be used as relaxants for pre-surgical anaesthesia
Midazolam
is a short-acting BZD used for brief
surgical procedures with local anaesthetic
Midazolam recovery
Recovery in a few hours with anterograde
amnesia – creates the illusion of anaesthesia
BZD Effects Lower incidence of (3)
tolerance,
less severe withdrawal,
greater safety margin than barbiturates
BZD use - like
Like barbiturates, the effects of BZDs vary with their rate of onset and duration of effect in the body.
BZDs have more rapid
onset and
termination of effect with increased
lipophilicity.
BZDs often have active
e metabolites
generated by type I metabolism
BZD Pharmacology
Some of the effects of BZDs relate to their slow metabolism and number of active metabolites
duration of effect of Benzos list
Oxazepam < Diazepam < Flurazepam
Diazepam half life
1-3 days but metabolites can be active and go on to have effects
Nordazepam results from _____ and has a half life of
Demethylation of Diazepam - half life of 2-7 days
Oxazepam results from _____ and has a half life of
oxidation and Demethylation of diazepam - half life of 4-15 days
temazepam results from _____ and has a half life of
oxidation of diazepam - half life of 4-18 days
prolonged action of metabolites
is beneficial for
anxiolytic and anticonvulsant use
Long elimination of metabolites reduces
reduces the
withdrawal syndrome
BZD metabolism - Short-acting BZDs
Enter the brain quickly due to high lipophilicity
Terminate quickly due to depot binding in fatty
tissues
BZD metabolism - Short-acting BZDs
- Enter the brain quickly due to high lipophilicity
- Terminate quickly due to depot binding in fatty
tissues - Tend to have ‘hangover’ effects due to slow release
from fatty tissues
BZD metabolism - Long-acting BZDs
- Slower onset due to lower lipophilicity
- Not readily taken up into fatty tissues
- Multiple active metabolites
- Long elimination half-lives
- Reduced withdrawal effects due to slow decline in
systemic levels
BZD receptor - BZD are
positive allosteric modulators at
the GABAA receptor
BZD site of GABAA is often referred to as
the BZD receptor
Many types of interactions at the BZD
receptor
- Agonists (+ allosteric modulator of GABAA)
- Partial agonists
- Antagonists
- Inverse agonists (- allosteric modulator of
GABAA)
Classic benzodiazepines act as
positive allosteric modulators of
GABA-A
BZD binding increases the
response of the channel to lower concentrations of GABA