Module 13: Sedative Hypnotics, Barbs, Benzos Flashcards
main inhibitory NT in the CNS
-Allows Cl- ions to pass thru post synaptic neuron making neuron less responsive to excitation –> causing sedation
GABA
1st prescribed benzo
thermally unstable
metabolized to Nordiazepam
Chlordiazepoxide
Used in Benzo ODs
Flumazenil
2 Analytical Challenges of Benzos
Polar, Thermally labile
Major site of absorption for Barbs:
Small intestine
Class of drugs with narrow therapeutic index (small diff btwn therapeutic and toxic)
Barbs
_____ + urea –> barbituric acid + H2O
Malonic Acid
Barb taken for migraines
Butalbital;
short-intermediate acting
Barb used in animal euthanasia
Pentobarbital;
short acting
Barb used to control seizures
Phenobarbital;
long acting;
therapeutic concentration: 15-40 mcg/mL
Prodrug that is a structural analog of phenobarbital
Primidone
Barb that is the target of most immunoassays
Secobarbital
Increasing lipid solubility _______ the potency and _______ duration of activity.
Increase; decreases
class of drugs that are weak acids, extensively metabolized in the liver, extract at pH of 5-7
Barbiturates
Barbs are classified based on their:
duration of action
One of the most important pharmacokinetic characteristics of barbiturates is their ability to:
Induce microsomal liver enzymes
(diminish drug action of other drugs that are metabolized by CYP450 enzymes)
Barbs: Hydroxylation at the _____ constituent is a common metabolic route.
C5b
Butalbital, amobarbital and pentobarbital have major ions at:
141 and 156
True/false: Common oxybarbiturates have mass spectral similarities based on their constituents at the C5 position.
True
Barbs: the major structural modification occurs at this position.
C5
Death following barbiturate intoxication is often due to:
Respiratory failure
The _______ barbiturates are used to induce surgical anesthesia:
Ultra-short acting
Barbs: This is the major inhibitory neurotransmitter in the brain.
GABA
True/False: Generally, benzodiazepines are highly protein bound.
True
Diazepam –> Nordiazepam
Dealkylation
True/False: Generally, benzodiazepines do not display a significant first-pass effect prior to distribution.
False - primarily metabolized in the liver
Adjusting the pH to _______ allows extraction of benzodiazepines into an immiscible organic solvent.
9-10 (think slightly basic)
For Benzos: Enzymatic hydrolysis is preferred over acidic hydrolysis because:
Some benzodiazepines are unstable in acid and rearrange to form benzophenones.
Benzodiazepine especially effective in managing panic disorder.
Alprazolam
Benzodiazepine used for the short term treatment of insomnia.
Temazepam
True/False: Lorazepam glucuronide accumulates in plasma and attains concentrations greater than lorazepam.
True
This benzodiazepine is relatively unstable in postmortem specimens due to bacterial and thermal degradation.
Clonazepam (think of how shitty it looks sometimes)
Tolerance to the sedative effects of benzodiazepines develops usually within a _______ of the initiation of therapy.
Week
This condition can significantly affect elimination of Benzos:
Renal Disease
What is the shortest acting benzodiazepine including their active metabolites.
Triazolam
Benzo effective in managing acute ethanol withdrawal.
Diazepam
Enzyme involved in the metabolism of many benzodiazepines.
CYP3A4
Benzodiazepines display _______ rather than generalized CNS depressant actions.
Selective
Benzo that can be missed by several commercially available immunoassay screening tests.
Lorazepam
The major binding protein for Benzos:
albumin
Clonazepam undergoes ______ to form 7-Aminoclonazepam.
Reduction
This drug is a derivative of imidazopyridine.
Zolpidem
Zolpidem differs from benzodiazepine drugs because:
Zolpidem binds specifically to the GABAA receptor subtypes
Glutethimide is structurally similar to this barbiturate.
Phenobarbital
