Anxiolytics & Hypnotics

Question 1

GABA-A receptor

Answer 1

*when activated, the GABA receptor opens to allow Cl- to flow INTRAcellularly, causing HYPERpolarization
*the hyperpolarization is what causes the inhibitory effect of GABA

Question 2

benzodiazepines MOA on GABA-A receptor

Answer 2

*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

Question 3

Z-drugs MOA on GABA-A receptor

Answer 3

*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

Question 4

barbiturates MOA on GABA-A receptor

Answer 4

*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

Question 5

actions/uses of benzodiazepines

Answer 5

*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)

Question 6

what characteristic can be used to distinguish the benzos from one another

Answer 6

wide variety in half-life

Question 7

metabolism of benzos

Answer 7

*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

Question 8

benzos - tolerance & dependence

Answer 8

*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)

Question 9

benzo’s effects on sleep

Answer 9

*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

Question 10

alprazolam - half-life

Answer 10

short/medium

Question 11

alprazolam - uses

Answer 11

commonly used for anxiety, acute panic

Question 12

diazepam - half-life

Answer 12

very long

Question 13

diazepam - uses

Answer 13

*alcohol withdrawal
*sedation
*IV or PO

Question 14

lorazepam - half-life

Answer 14

short/medium

Question 15

lorazepam - uses

Answer 15

*alcohol withdrawal
*sedation
*status epilepticus
*IV or PO

Question 16

clonazepam - half-life

Answer 16

medium

Question 17

clonazepam - uses

Answer 17

*seizures
*anxiety
*panic

Question 18

midazolam - half-life

Answer 18

very short

Question 19

midazolam - uses

Answer 19

*anesthesia
*conscious sedation
*status epilepticus
*sedation
*often given as IV infusion (but can also be IM)

Question 20

benzos - adverse effects

Answer 20

*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)

Question 21

zolpidem

Answer 21

*important “Z-drug” to know
*aka ambien

Question 22

important z-drug to know

Answer 22

zolpidem

Question 23

z-drugs - half-life

Answer 23

short

Question 24

z-drugs - use

Answer 24

*sleep/hypnotic
*less adverse effect on stages of sleep (compared to benzos)

Question 25

z-drugs - adverse effects

Answer 25

*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"

Question 26

what drug is used to reverse the actions of benzos/z-drugs

Answer 26

flumazenil

Question 27

flumazenil

Answer 27

*REVERSIBLE benzo-receptor antagonist (reverses effects of benzos and z-drugs)

Question 28

flumazenil - uses

Answer 28

*reverse benzo used in surgery or procedure *treat overdose with benzos or z-drugs

Question 29

flumazenil - ADEs

Answer 29

*agitation, confusion, dizziness *can precipitate abstinence symptoms

Question 30

flumazenil - half-life

Answer 30

*short (about 1 hour) *may have to give repeated doses

Question 31

barbiturates - uses

Answer 31

*ANESTHESIA *peds neuro *some ICU sedation

Question 32

barbiturates - adverse effects

Answer 32

*sedation!! *dependence (worse than benzos) *tolerance *induction of hepatic enzymes (drug interactions) *respiratory depression

Question 33

barbiturates - key terms to associate with

Answer 33

*sedation *seizures (peds) *enzyme-induction *GABA

Question 34

buspirone - MOA

Answer 34

*unique (but uncertain) MOA: hits some 5-HT and DA receptors

Question 35

buspirone

Answer 35

*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)

Question 36

dual orexin receptor antagonists (DORAs) - MOA

Answer 36

*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

Question 37

dual orexin receptor antagonists (DORAs) - drugs in class

Answer 37

*suvorexant *lemborexant *daridorexant

Question 38

dual orexin receptor antagonists (DORAs) - uses and advantages

Answer 38

*used for sleep *advantages: better daytime functioning; no rebound or withdrawal; little risk of abuse or dependence *note - not used much

Question 39

remelteon

Answer 39

*melatonin receptor agonist *improves sleep latency (a little); does not improve sleep maintenance *ADEs: dizziness, somnolence, fatigue *does not affect sleep architecture

Question 40

miscallaneous meds used for insomnia

Answer 40

*diphenhydramine (Benadryl - an H1 antagonist) *Trazodone - sedating antidepressant *gabapentin *melatonin *alcohol

Question 41

treating a patient with insomnia

Answer 41

*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

Question 42

treating a patient with anxiety

Answer 42

*counseling first (CBT) *meds: usually treated with serotonergic-acting antidepressant -buspirone and gabapentin can be adjuncts -benzos second-line &/or when rapid action needed