Sedative Hypnotics Flashcards
How are benzodiazepenes metabolized?
Hepativ. P450 enzymes especially CYP3A4
What barbiturate is excreted unchanged into the urine to a certain extent (20-30% in humans)? It also has an eliminiation half life of 4-5 days
Phenobarbital
How can the excretion of Pb be hastened?
Alkalinize the urine because Pb is weakly acidic
Where does Ramelteon act?
MT1 and MT2 melatonin receptors in the suprachiasmatic nucleus of the brain
What receptors does busiprone act on?
D2 and 5HT1A
How do benzodiazepenes and barbiturates affect liver metabolizing enzymes? State the difference
Barbiturates can increase the activity of these enzymes while benzos have no effect. So Pb can induce its own metabolism in the long run
What type of GABA receptor do benzos and barbiturates bind to?
How about baclofen?
GABA A
GABA B
How do the actions of Benzos and Barbs differ at GABA A?
Benzos increase frequency of opneing GABA gated chloride channels
Barbs increase duration
What additional effects do barbiturates have that make them have more pronounced central depressant effects compared to benzos?
Depress actions of glutamic acid via binding to the AMPA receptor
Identify the mediated actions of the different GABA A receptors.
alpha 1 sedation and amnesia
alpha 2 and 3 for anxiolysis and muscle relaxation
alpha 5 memory
What kind of amnesia do benzos and barbs produce?
Anterograde
What stages of sleep are reduced by benzos and barbs?
REM and Stage 4 NREM
Stage 2 NREM is increased
The general effects of benzodiazepines and older
sedative-hypnotics on patterns of normal sleep are as follows: (1) the latency of sleep onset is decreased (time to fall asleep); (2) the duration of stage 2 NREM (nonrapid eye movement) sleep is increased; (3) the duration of REM sleep is decreased; and (4) the duration of stage 4 NREM slow-wave sleep is decreased.
What barbiturate is used for anesthesia owing to its high lipid solubility– great for induction?
Thiopental
What is the most dangerous effect of sedative hyponotic drug doses?
Cardiovascular and respiratory collapse
What is the expected adverse effect of benzos and barbs at doses meant to treat anxiety?
Disinhibition
What is the antidote to benzo overdose and how does it act?
Flumazenil acting as a competitive antagonist at the GABA A receptor– blocking the effects of benzos and even the newer sedatives like zolpidem
Why are zolpidem and other new sleeping pills like Zaleplon and Eszopiclone better than benzos?
Minimal change in sleep pattern. Also they have few amnestic effects and day after psychomotor depression or somnolence. Remember that Benzos decrease REM and slow wave stage 4 NREM sleep.
What disease are barbiturates contraindicated in because of enhanced porphyrin synthesis?
Porphyria: Acute intermittent, variegate, symptomatic
MOA of The newer hypnotics: Zolpidem, Zaleplon, Eszopiclone
Similar to Benzos– bind to GABA A– bind between the alpha and gamma receptors
What is the advantage of busiprone over benzos in anxiety?
Minimal psychomotor impairment and no additive CNS depression
Why do oxazepam and lorazepam have relatively short half-lives?
They are metabolized directly into inactive glucuronides VS diazepam, Flurazepam
THEY HAVE NO ACTIVE METABOLITES! LIKE ZOLPIDEM
What is the elimination half life of phenobarbital?
4-5 days!
Diazepam 1-2 days half life
What are the 3 characteristics of Ramelteon that make it ideal for use as a hypnotic substance?
- Reduced latency of persistent sleep with no effects on sleep architecture
- No rebound insomnia
- No significant withdrawal symptoms
Why is busiprone NOT suitable for the management of acute anxiety?
Effects may take more than a week to become established
