Sleep Flashcards
Properties of Ideal Hypnotic Agent
Rapidly induce sleep – influenced by rate of absorption
Sufficient duration to maintain sleep – influenced by t1/2
No tolerance development with repeated use
No rebound insomnia with abrupt d/c - influenced by t1/2
High therapeutic index
Normalize disturbed sleep without disturbing normal sleep
“Z”-drugs (zolpidem) closest to ideal
Night terrors are
Stage 3
“Z”-Drugs
Eszoplicone
Zaleplon
Zolpidem
Benzodiazepines
Triazolam
Temazepam
Flurazepam
Non-GABA Actions
Ramelteon - Melatonin
Trazodone
Diphenhydramine
Chloral hydrate
Hypotnitic vs anx benzo=
(↑ dose= sleep, lower dose = ↓ anx)
dose
BDZs enhance channel opening in presence of _____only
GABA
BARBs prolong channel opening in presence of GABA and at higher doses _____________
open channel directly
Less hangover effect w/
short half life
Rebound insomnia has?
short half life
Triazolam (Halcion)
Benzodiazepine Pharmacokinetics
Rapid oral absorption
Short t1/2: 1.5-5 hrs - eliminated in 1 dosing cycle
Less daytime sedation (hangover)
Rebound insomnia next day due to rapid elimination
Temazepam (Restoril)
Benzodiazepine Pharmacokinetics
Slow absorption - minimal effect on sleep latency
Intermediate t1/2 (9-13 hrs)
Flurazepam (Dalmane)
Benzodiazepine Pharmacokinetics
Long t1/2 + active metabolite (75-90 hrs) - low tolerance
Can accumulate in elderly - impaired hepatic clearance daytime sedation (“hangover”) / overdosage
Zolpidem (Ambien) and Zaleplon (Sonata)
Rapid oral absorption
Shortest durations of action (6-8 hours) and half-lives of available agents (zolpidem: 2-2.5 hrs - zaleplon: 1 hr)
Zolpidem eliminated more slowly in females - dose recommendation halved to prevent daytime hangover
Z drug
Eszopiclone (Lunesta)
Structurally different from zolpidem or zaleplon with longer t1/2 ( 6 hrs)
z drug
Recommendations for Treatment of Insomnia
Nondrug measures emerging as preferred treatment
Cognitive behavioral therapy – alone or with drug
Drug treatment also first-line option
Nonbenzodiazepines (Z-drugs, ramelteon)
Shorter-acting BDZs (temazepam)
Lowest effective dose – taper when possible
Address underlying causes: sleep apnea, pain, restless leg syndrome, anxiety or depression
Check that stimulating (caffeine, decongestants, stimulants, SSRIs) or sleep-interrupting meds (diuretics) not taken hs
Serotonin receptor antagonist and reuptake blocker
Decrease in REM sleep – no change or increase in SWS
ADRs: Oversedation, orthostasis (α-1 block), priapism (rare but serious)
Role: An antidepressant – very sedating and improves sleep continuity
No concerns with tolerance or dependence if abuse concerns with patient
Often used empirically for insomnia, but efficacy in non-depressed patients uncertain
Trazodone
Agonist at melatonin receptors
MT1 (induce sleepiness) and MT2 (regulate circadian rhythms)
ADRs (
Ramelteon
• Antagonist at CNS histamine-H1 and muscarinic receptors
• ADRs: Generally minimal, BUT antimuscarinic actions can be troublesome, especially in elderly
• Role
Minimally effective, generally NOT recommended long-term
Can see tolerance after > 10 days use – consider “off” night after 3 days of use to reduce tolerance
Diphenhydramine - Doxylamine
Both benzodiazepines (e.g., temazepam [Restoril]) and non-benzodiazepines (e.g., zolpidem [Ambien]) are used in the treatment of insomnia. All of the pharmacologic properties listed below are shared by both classes of drugs, except that only zolpidem:
Produces additive CNS depression if taken with ethanol- yes
Can produce tolerance and dependence (controlled substance)- z less but can sched 4
Has a high therapeutic index relative to barbiturates- both
Can cause anterograde amnesia- both
Binds selectively to GABA receptors containing the α1 subunit- only z drug ***
