drugs for insomnia Flashcards
what are the 2 main goals of treating insomnia?
improvement in nighttime and daytime symptoms
most drugs used to treat insomnia are considered __________ __________
off label
which drugs are approved for insomnia?
benzodiabepines, BNZ receptors agonists (zolipidem), Melatnonin receptor agonists (e.g. remelteon)
how do each of the drug classes used to treat insomnia affect the response pattern of the GABA receptors?
the different drug classes modifies the response pattern of the GABA receptor to endogenous ligand
at very high doses, which drug class is capable of activating and opening the GABA-A channel?
barbituates
at normal clinical doses, do any of the drug classes used to treat insomnia cause opening of the endogenous GABA channel?
no
how are benzodiazepines or benzodiazepine receptor agonists different in respect to endogenous GABA action?
the benzodiazepines or benzodiazepine receptor agonist produces only an allosteric modification, leading to leftward shift in the dose response curve to endogenous GABA action (they have ceiling effect)
benzodiazepines are only lethal when consumed with quantities of what?
alcohol
what are some of the adverse effects of BNZs the morning after?
sedation, cognitive impairment, rebound insomnia
what are some of the adverse effects of BNZ withdrawal?
anxiety, irritability, restlessness, OSA, severe ventilatory impairment, tapered withdrawal
what are 2 attributes that you would like to have in a drug used to treat insomnia?
- drug with a rapid onset time
2. drug that has durability of action that pts don’t wake up in the middle of the night
Benzodiazepine receptor agonists seem capable only of sedative and amnesic actions via ________ receptor complex at normal clinical doses
BZ-1
Cumulative and residual effects like excessive drowsiness are less of a problem with benzodiazepines like what 3 drugs?
estazolam, oxazepam, lorazepam, have short half-lives and are metabolized directly to inactive glucuronides
what pregnancy category are benzodiazepines?
category X
what are some of the contraindications for the benzodiazepines?
COPD, closed angle glaucoma, CNS drugs, driving, and depression
which BNZ is rapidly inactivated?
triazolam
which 2 BNZs have metabolites that accumulate?
Flurazepam, Quazepam
which BNZ has CYP2B6 > 3A4 interactions?
quazepam
which BNZ doesn’t have CYP interactions bc it is conjugated metabolically?
temazepam
3 of the BNZs have interactions with CYP3A4, what are they?
estazolam, flurazepam, triazolam
the benzodiazepine receptor agonists are considered what pregnancy category?
Pregnancy Category C
which benzodiazepine receptor agonist has interactions with aldehyde dehydrogenase?
zaleplon
name the 3 Benzodiazepine receptor agonists?
Zolpidem
Zaleplon
Eszopiclone
what is the only drug approved for middle of the night awakening?
zolpidem (administered solely as a short acting product)
Which Benzodiazepine receptor agonist is available in both sublingual and oral spray preps for increased onset of action?
zolpidem
what is the most widely prescribed hypnotic in the US?
zolpidem
why can’t you chew the oral benzodiazepine receptor agonists?
the action is reliant on the tablet integrity
which drug has new dosing recommendations for women due to diminished elimination rate compared to women?
zolpidem (dose reduced)
which population of pts are more likely to experience residual effects of zolpidem the next day?
women, b/c women eliminate the drug more slowly than men do
how are the benzodiazepine receptor agonists metabolized?
hepatically with various CYP interactions
what is the mechanisms of action of flumazenil?
BNZ & benzodiazepine receptor agonist— antagonist, given IV
what is the result of melatonin binding to MT1 receptors?
attenuates SCN activity & induces sleep
what is the result of melatonin binding to MT2 receptors?
maintains circadian rhythm
which melatonin receptor is not involved in sleep regulation?
MT3
what type of receptors are MT1 and MT2, and where can they be found?
G -protein coupled receptors found in the CNS
MOA of Ramelteon
melatonin receptor agonist
what are the benefits of ramelteon?
not associated with residual effects, no abuse potential or respiratory depression
how is ramelteon metabolized?
CYP1A2> 2C9, 3A4
what are some of the adverse effects of ramelteon?
headache, somnolence, nausea, insomnia, naso-pharyngitis, URTI w/ long term use
what is the only FDA approved antidepressant used to treat insomnia?
doxepin
name the drug: antidepressant with primarily an anti-histaminergic action at low doses
doxepin
what is an adverse effect of using doxepin to treat insomnia?
has residual effects the next day
which antidepressant used to treat insomnia has significant alpha-2 antagonism, reinforcing NE, 5-HT release?
mirtazapine
what are 2 antidepresants used to treat insomnia that have a strong effect of sedation but very little effect on muscarinic block, NE, reuptake block, or 5-HT reuptake block?
mirtazapine & trazodone
antidepressants used to treat insomnia have a BBW for what?
suicidal ideation
name the 3 antidepressants used to treat insomnia?
doxepin
mirtazapine
trazodone
you should be cautious of prescribing antidepressants to pts with a history of what?
psychotic disorders
what are some of the antimuscarinic adverse effects of the first generation antihistamines?
xerostomia, blurred vision, urinary retention, increased intraocular pressure
what is a major downside to using 1st gen. antihistamines for insomnia?
rapid tolerance may develop to sedative action
what are the two 1st. gen. antihistamines used for insomnia?
diphenhydramine & doxylamine
why do you try to avoid using 1st gen. antihistamines in the elderly?
because of excessive sedation, urinary retention (anticholinergic effect) and falls producing injury
note also caution w/ Narrow-angle glaucoma
name some drugs that can produce insomnia?
TCAs, MAOis, SSRIs, Venlafaxine, Buproprion, Levodopa, Felbamate, beta-blockers, decongestants, antibiotics, asthma meds, stimulants
what is the most commonly used alternative medicine for insomnia?
chamomile
