Pharm: Sedatives/hypnotics Flashcards
which drugs undergo oxidation reactions, thus requiring good hepatic function?
Alprazolam, Diazepam
which drug has longest half life?
Diazepam - distributes into CNS!
which drugs are best for those w/ hepatic impairment?
lorazepam, oxazepam, temezapam - these are all conjugated rather than oxidized
which drugs are best for sleep aids?
those with short half lives - Eszopiclone, Zaleplon, Zolpidem
flumazenil
- benzodiazapine antagonist
MOA: competitive antagonist at benzodiazepine site on GABAA receptor
Blocks actions of – benzodiazepines, zolpidem, zaleplon, and eszopiclone
Does not block – barbiturates, buspirone, ramelteon
PK: short t1/2 0.7-1.3 hours (imp. b/c the benzodiazepine has longer 1/2 life, so must give repeat doses)
Use: reversing CNS depressant effects of benzodiazepine overdose and shorten recovery following anesthetic and diagnostic procedures
ADRs: agitation, confusion, dizziness, nausea
what can flumazenil block?
– benzodiazepines, zolpidem, zaleplon, and eszopiclone
Does not block:
– barbiturates, buspirone, ramelteon
buspirone
MOA: unknown; mediated through serotonergic or dopaminergic systems
PK: extensive first-pass effect, extensive metabolism (CYP3A4)
Use: generalized anxiety disorder (3-4 weeks to become established)
NOTE: does not produce sedation or hypnosis or euphoria!!!
ADRs: tachycardia, palpitations, nervousness, GI distress, paresthesias
ramelteon
MOA: agonist at MT1 and MT2 melatonin receptors
PK: extensive first-pass effect
Use: treatment of insomnia (difficulty with sleep onset)
ADRs: dizziness, somnolence, fatigue
what do you use sedatives for?
Relief of anxiety
Insomnia
Sedation and amnesia before and during medical surgical procedures
Treatment of epilepsy and seizure states
Component of balanced anesthesia (IV administration)
Control of ethanol or other sedative-hypnotic withdrawal states
Muscle relaxation in specific neuromuscular disorders
Diagnostic aids or for treatment in psychiatry
tx of acute anxiety and rapid tx of panic attacks?
benzodiazepine
Advantages:
High therapeutic index
Antagonist available for overdose (flumazenil)
Low risk of drug-drug interactions
Minimal effect on CV and autonomic function
Disadvantages:
Risk of dependence
CNS depression
Amnesic effects
** for more generalized and chronic relief you wouldn’t use this
what to use for sleep disorder tx?
Sleep aids should decrease sleep latency and provide sufficient sleep duration with minimal hangover effects
**Benzodiazepines used but daytime sedation a disadvantage- not as good
Zolpidem, zaleplon, and eszopiclone
- Highly effective
- Rapid onset with minimal hangover effects
- Zolpidem in biphasic release formulation for sustained sleep maintenance
- Zaleplon and zolpidem act rapidly
- Eszopiclone has a longer half-life
what to use for sleep disorder tx?
Sleep aids should decrease sleep latency and provide sufficient sleep duration with minimal hangover effects
**Benzodiazepines used but daytime sedation a disadvantage- not as good
Zolpidem, zaleplon, and eszopiclone
- Highly effective
- Rapid onset with minimal hangover effects
- Zolpidem in biphasic release formulation for sustained sleep maintenance
- Zaleplon and zolpidem act rapidly
- Eszopiclone has a longer half-life
sedative vs. hypnotic?
Sedative
- Reduces anxiety, exerts calming effect
- May be side effect of drugs which are not general CNS depressants (e.g., antidepressants, antihistamines, neuroleptics/antipsychotics)
Hypnotic
- Produces drowsiness, facilitates onset & maintenance of sleep
- More pronounced CNS depression
which drugs have a linear dose response curve?
barbiturates, alcohols, and older sedative-hypnotics
NOTE: benzodiazepines and newer sedative-hypnotics (plateau) — thus harder to reach the state of coma and death w/ dosing in these drugs
30 y/o ddx with generalized anxiety disorder. physician writes drug for lorazepam, what is its anxiolytic properties MOA?
its a benzo, it increases frequency of GABA channel opening –> increased Cl- influx –> increased hyperpolarization
30 y/o ddx with generalized anxiety disorder. physician writes drug for lorazepam, what is its anxiolytic properties MOA?
its a benzo, it increases frequency of GABA channel opening –> increased Cl- influx –> increased hyperpolarization
25 y/o presents w/ c/o excessive anxiety, has difficulty concentrating, often tired, doesn’t sleep well, alcohol dependence hx, doesn’t want sexual performance problems… what agent is most appropriate?
- Busiprone, fluoxetine, impipramine, lorazepam?
Answer: Busiprone: doesn’t cause sedation, hypnosis or euphoria!! though this will take 3-4 weeks to work
- Fluoxetine: SSRI - assoc. w/ sex dysfunction (though usually this is preferred for first line….)
- Imipramine: TCA - assoc. w/ anticholinergic effects
- Lorazepam: associated w/ physiologic dependence, thus d/t hx of alcohol dependence, wouldn’t want to put him on this that could produce dependence again
- Propanolol: doesn’t work
37 y/o w/ c/o diff. falling asleep. which of following is used to tx insomnia but has no affinity for GABA receptor complex?
- eszoplicone, ramelteon, temazepam, zaleplon, zolpidem?
Ramelteon doesn’t bind gaba complex - this works through melatonin receptors!
37 y/o for insomnia, which isn’t metabolized extensively via hepatic oxidation to longer acting metabolite and would be good for NOT producing a hangover effect?
- chlorodiazepine, clorazepate, diazepam, flurazepam, lorazepam
** answer lorazepam - metabolized via conjugation and excreted via kidney
LOT drugs: lorazepam, oxazepam, tomazepam are conjugated before excretion w/ no active metabolites - these drugs would be useful for liver failure!!!!
* also useful in elderly who are more sensitive to sedative hypnotics, don’t want drugs w/ active metabolites that can cause cumulative toxicity
44 y/o on hypnotic sleep aids, one week later she wakes up in her PJs in jail after enjoying a glass of wine - she wrecked her car and was under the influence. what drug did FDA req. add’n warnings d/t reports of “sleep-driving”?
Ambien/Zolpidem - increased reports of sleep walking!
32 y/o y/o unresponsive w/ pill overdose. BP 115/74, slurred speech, RR 12, pupils normal size, normal bowel tones, impaired cognition?? which drug is most imp for this pt?
- atropine, ethanol, fluazenil, naloxone
sx point to benzo OD - confusion, blurred vision, drowsiness, unresponsiveness, slurred speech amnesia
(opioids cause constriction, use naloxone to reduce this….. ACHE inhibitors also cause constriction, would give atropine for this…)
Answer: Flumazenil
alprazolam
- benzodiazapine
MOA: promotes binding of GABA to GABAa receptor - increasing frequency of Cl - channel opening
USE: sedation, hypnosis, muscle relaxation, anxiolytic, and anticonvulsant effects
** high anxiolytic potency, w/ low capacity to cause fatal CNS depression (replaced barbituates)
ADR: hepatic excretion, need good liver!
clonazepam
- benzodiazapine
MOA: promotes binding of GABA to GABAa receptor - increasing frequency of channel opening
USE: sedation, hypnosis, muscle relaxation, anxiolytic, and anticonvulsant effects
** high anxiolytic potency, w/ low capacity to cause fatal CNS depression (replaced barbituates)
diazepam
- benzodiazapine
MOA: promotes binding of GABA to GABAa receptor - increasing frequency of channel opening
USE: sedation, hypnosis, muscle relaxation, anxiolytic, and anticonvulsant effects
** high anxiolytic potency, w/ low capacity to cause fatal CNS depression (replaced barbituates)
ADR: undergoes oxidation, need good liver function!
