Anxiolytics & Hypnotics Flashcards
GABA-A receptor
*when activated, the GABA receptor opens to allow Cl- to flow INTRAcellularly, causing HYPERpolarization
*the hyperpolarization is what causes the inhibitory effect of GABA
benzodiazepines MOA on GABA-A receptor
*benzos bind allosterically (same site as the z-drugs) to the GABA-A receptor, facilitating the binding of GABA to the receptor
*benzos increase the FREQUENCY of the channel being open
Z-drugs MOA on GABA-A receptor
*Z-drugs bind allosterically (same site as benzos) to the GABA-A receptor, facilitating the binding of GABA to the receptor
*Z-drugs increase the FREQUENCY of the channel being open
barbiturates MOA on GABA-A receptor
*barbs bind allosterically to the GABA-A receptor, facilitating the binding of GABA to the receptor
*barbs increase the DURATION of the channel being open
actions/uses of benzodiazepines
*sedation, sleep; conscious sedation, anesthesia adjuvant; acute anxiety
*muscle relaxation
*treatment of seizures
*alcohol withdrawal
*anterograde amnesia (loss of the ability to create new memories)
what characteristic can be used to distinguish the benzos from one another
wide variety in half-life
metabolism of benzos
*all metabolized in LIVER
-some undergo Phase I metabolism to ACTIVE metabolites
-long-acting agents can be even MORE long-acting in the elderly or those taking interacting meds
benzos - tolerance & dependence
*tolerance with repeated usage (mostly related to down-regulation of brain benzo receptors)
*psychological dependence
*physical dependence (need to take drug to prevent withdrawal symptoms); depends on:
-dose prior to cessation
-drug elimination (short half-life drugs are worse)
benzo’s effects on sleep
*reduction in sleep latency
*suppression of REM sleep
*decreases in all components of sleep EXCEPT STAGE 2
*development of tolerance to sleep effects with continued use
*can produce “REM rebound” upon abrupt discontinuation, especially for short-acting agents at high doses
alprazolam - half-life
short/medium
alprazolam - uses
commonly used for anxiety, acute panic
diazepam - half-life
very long
diazepam - uses
*alcohol withdrawal
*sedation
*IV or PO
lorazepam - half-life
short/medium
lorazepam - uses
*alcohol withdrawal
*sedation
*status epilepticus
*IV or PO
clonazepam - half-life
medium
clonazepam - uses
*seizures
*anxiety
*panic
midazolam - half-life
very short
midazolam - uses
*anesthesia
*conscious sedation
*status epilepticus
*sedation
*often given as IV infusion (but can also be IM)
benzos - adverse effects
*sedation beyond what was intended (diminished motor skills, judgement, etc)
*anterograde amnesia (cannot retain new info)
*not very “toxic” given alone, but problems arise:
-respiratory depression in pts with pulmonary disease
-given with other drugs (alcohol, narcotics, other CNS depressants)
*be especially cautious with elderly (avoid if possible)
zolpidem
*important “Z-drug” to know
*aka ambien
important z-drug to know
zolpidem
z-drugs - half-life
short
z-drugs - use
*sleep/hypnotic
*less adverse effect on stages of sleep (compared to benzos)
z-drugs - adverse effects
*similar to benzos
-less intensive withdrawal symptoms
-generally less tolerance and dependence
*rebound insomnia with higher doses
*perhaps a bit “safer” in the elderly, but not really “safe”
what drug is used to reverse the actions of benzos/z-drugs
flumazenil
flumazenil
*REVERSIBLE benzo-receptor antagonist (reverses effects of benzos and z-drugs)
flumazenil - uses
*reverse benzo used in surgery or procedure
*treat overdose with benzos or z-drugs
flumazenil - ADEs
*agitation, confusion, dizziness
*can precipitate abstinence symptoms
flumazenil - half-life
*short (about 1 hour)
*may have to give repeated doses
barbiturates - uses
*ANESTHESIA
*peds neuro
*some ICU sedation
barbiturates - adverse effects
*sedation!!
*dependence (worse than benzos)
*tolerance
*induction of hepatic enzymes (drug interactions)
*respiratory depression
barbiturates - key terms to associate with
*sedation
*seizures (peds)
*enzyme-induction
*GABA
buspirone - MOA
*unique (but uncertain) MOA: hits some 5-HT and DA receptors
buspirone
*relieves anxiety without much sedative or euphoric effect
*no rebound anxiety or withdrawal sx with abrupt discontinuation
*takes 2-4 weeks to see effects
*ADE: tachycardia, GI distress, paresthesias
*perhaps not as potent as you would like (often used as an adjunct with other meds)
dual orexin receptor antagonists (DORAs) - MOA
*blocks OX1R and OX2R receptors (decreases the downstream action of the wake-promoting neurotransmitters that are overactive in pts with insomnia)
-Orexin A and B are peptides in hypothalamic neurons involved in control of wakefulness; they are silent during sleep
dual orexin receptor antagonists (DORAs) - drugs in class
*suvorexant
*lemborexant
*daridorexant
dual orexin receptor antagonists (DORAs) - uses and advantages
*used for sleep
*advantages: better daytime functioning; no rebound or withdrawal; little risk of abuse or dependence
*note - not used much
remelteon
*melatonin receptor agonist
*improves sleep latency (a little); does not improve sleep maintenance
*ADEs: dizziness, somnolence, fatigue
*does not affect sleep architecture
miscallaneous meds used for insomnia
*diphenhydramine (Benadryl - an H1 antagonist)
*Trazodone - sedating antidepressant
*gabapentin
*melatonin
*alcohol
treating a patient with insomnia
*best treatment is improving sleep hygiene
*meds only play an adjunct role, especially for chronic insomnia
*drug-induced sleep just isn’t as good as natural sleep
*with continued med use, benefit often decreases as potential for ADEs increases
treating a patient with anxiety
*counseling first (CBT)
*meds: usually treated with serotonergic-acting antidepressant
-buspirone and gabapentin can be adjuncts
-benzos second-line &/or when rapid action needed
