drugs for insomnia

Question 1

what are the 2 main goals of treating insomnia?

Answer 1

improvement in nighttime and daytime symptoms

Question 2

most drugs used to treat insomnia are considered __________ __________

Answer 2

off label

Question 3

which drugs are approved for insomnia?

Answer 3

benzodiabepines, BNZ receptors agonists (zolipidem), Melatnonin receptor agonists (e.g. remelteon)

Question 4

how do each of the drug classes used to treat insomnia affect the response pattern of the GABA receptors?

Answer 4

the different drug classes modifies the response pattern of the GABA receptor to endogenous ligand

Question 5

at very high doses, which drug class is capable of activating and opening the GABA-A channel?

Answer 5

barbituates

Question 6

at normal clinical doses, do any of the drug classes used to treat insomnia cause opening of the endogenous GABA channel?

Answer 6

no

Question 7

how are benzodiazepines or benzodiazepine receptor agonists different in respect to endogenous GABA action?

Answer 7

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)

Question 8

benzodiazepines are only lethal when consumed with quantities of what?

Answer 8

alcohol

Question 9

what are some of the adverse effects of BNZs the morning after?

Answer 9

sedation, cognitive impairment, rebound insomnia

Question 10

what are some of the adverse effects of BNZ withdrawal?

Answer 10

anxiety, irritability, restlessness, OSA, severe ventilatory impairment, tapered withdrawal

Question 11

what are 2 attributes that you would like to have in a drug used to treat insomnia?

Answer 11

1. 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

Question 12

Benzodiazepine receptor agonists seem capable only of sedative and amnesic actions via ________ receptor complex at normal clinical doses

Answer 12

BZ-1

Question 13

Cumulative and residual effects like excessive drowsiness are less of a problem with benzodiazepines like what 3 drugs?

Answer 13

estazolam, oxazepam, lorazepam, have short half-lives and are metabolized directly to inactive glucuronides

Question 14

what pregnancy category are benzodiazepines?

Answer 14

category X

Question 15

what are some of the contraindications for the benzodiazepines?

Answer 15

COPD, closed angle glaucoma, CNS drugs, driving, and depression

Question 16

which BNZ is rapidly inactivated?

Answer 16

triazolam

Question 17

which 2 BNZs have metabolites that accumulate?

Answer 17

Flurazepam, Quazepam

Question 18

which BNZ has CYP2B6 > 3A4 interactions?

Answer 18

quazepam

Question 19

which BNZ doesn’t have CYP interactions bc it is conjugated metabolically?

Answer 19

temazepam

Question 20

3 of the BNZs have interactions with CYP3A4, what are they?

Answer 20

estazolam, flurazepam, triazolam

Question 21

the benzodiazepine receptor agonists are considered what pregnancy category?

Answer 21

Pregnancy Category C

Question 22

which benzodiazepine receptor agonist has interactions with aldehyde dehydrogenase?

Answer 22

zaleplon

Question 23

name the 3 Benzodiazepine receptor agonists?

Answer 23

Zolpidem
Zaleplon
Eszopiclone

Question 24

what is the only drug approved for middle of the night awakening?

Answer 24

zolpidem (administered solely as a short acting product)

Question 25

Which Benzodiazepine receptor agonist is available in both sublingual and oral spray preps for increased onset of action?

Answer 25

zolpidem

Question 26

what is the most widely prescribed hypnotic in the US?

Answer 26

zolpidem

Question 27

why can't you chew the oral benzodiazepine receptor agonists?

Answer 27

the action is reliant on the tablet integrity

Question 28

which drug has new dosing recommendations for women due to diminished elimination rate compared to women?

Answer 28

zolpidem (dose reduced)

Question 29

which population of pts are more likely to experience residual effects of zolpidem the next day?

Answer 29

women, b/c women eliminate the drug more slowly than men do

Question 30

how are the benzodiazepine receptor agonists metabolized?

Answer 30

hepatically with various CYP interactions

Question 31

what is the mechanisms of action of flumazenil?

Answer 31

BNZ & benzodiazepine receptor agonist--- antagonist, given IV

Question 32

what is the result of melatonin binding to MT1 receptors?

Answer 32

attenuates SCN activity & induces sleep

Question 33

what is the result of melatonin binding to MT2 receptors?

Answer 33

maintains circadian rhythm

Question 34

which melatonin receptor is not involved in sleep regulation?

Answer 34

MT3

Question 35

what type of receptors are MT1 and MT2, and where can they be found?

Answer 35

G -protein coupled receptors found in the CNS

Question 36

MOA of Ramelteon

Answer 36

melatonin receptor agonist

Question 37

what are the benefits of ramelteon?

Answer 37

not associated with residual effects, no abuse potential or respiratory depression

Question 38

how is ramelteon metabolized?

Answer 38

CYP1A2> 2C9, 3A4

Question 39

what are some of the adverse effects of ramelteon?

Answer 39

headache, somnolence, nausea, insomnia, naso-pharyngitis, URTI w/ long term use

Question 40

what is the only FDA approved antidepressant used to treat insomnia?

Answer 40

doxepin

Question 41

name the drug: antidepressant with primarily an anti-histaminergic action at low doses

Answer 41

doxepin

Question 42

what is an adverse effect of using doxepin to treat insomnia?

Answer 42

has residual effects the next day

Question 43

which antidepressant used to treat insomnia has significant alpha-2 antagonism, reinforcing NE, 5-HT release?

Answer 43

mirtazapine

Question 44

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?

Answer 44

mirtazapine & trazodone

Question 45

antidepressants used to treat insomnia have a BBW for what?

Answer 45

suicidal ideation

Question 46

name the 3 antidepressants used to treat insomnia?

Answer 46

doxepin mirtazapine trazodone

Question 47

you should be cautious of prescribing antidepressants to pts with a history of what?

Answer 47

psychotic disorders

Question 48

what are some of the antimuscarinic adverse effects of the first generation antihistamines?

Answer 48

xerostomia, blurred vision, urinary retention, increased intraocular pressure

Question 49

what is a major downside to using 1st gen. antihistamines for insomnia?

Answer 49

rapid tolerance may develop to sedative action

Question 50

what are the two 1st. gen. antihistamines used for insomnia?

Answer 50

diphenhydramine & doxylamine

Question 51

why do you try to avoid using 1st gen. antihistamines in the elderly?

Answer 51

because of excessive sedation, urinary retention (anticholinergic effect) and falls producing injury note also caution w/ Narrow-angle glaucoma

Question 52

name some drugs that can produce insomnia?

Answer 52

TCAs, MAOis, SSRIs, Venlafaxine, Buproprion, Levodopa, Felbamate, beta-blockers, decongestants, antibiotics, asthma meds, stimulants

Question 53

what is the most commonly used alternative medicine for insomnia?

Answer 53

chamomile