CNS sedative-hypnotics/Anti-anxiety agents

Question 1

Benzodiazepines (names)

Answer 1

diazepam
alprazolam
chlordiazepoxide
lorazepam
midazolam

Question 2

benzodiazepine therapeutic uses

Answer 2

sedative-hypnotic: insomnia
anxiolytic: anxiety, OCD, phobias
Muscle relaxant: spasticity, dystonias
anticonvulsant: seizures (absence), epipeticus, rapid tolerance here
other: pre-op med, endoscopic procedures, w/d from ETOH or CNS depressants

Question 3

benzodiazepine MOA

Answer 3

bind GABA-A receptors on gamma or delta sub-unit in limbic system enhancing neuronal inhibition, likely produces anxiolytic effects
-increases frequency of GABAR opening in presence of GABA

Question 4

flumazenil

Answer 4

blocks effects of GABA agonists
-competitive inhibition at benzodiazepine binding site
used to reverse SE of benzos and benzo-like substances

Question 5

metabolism of benzos

Answer 5

not active upon absorption, undergo phase I reactions in liver–> active metabolites
-phase II reactions conjugate drugs into inactive metabolites via CYPs (P450) and they are excreted in urine

Question 6

half life of benzos: alprazolam, diazepam, lorazepam, midaz

Answer 6

alp: short (12-15h): insomnia/anxiety
dia: long (30-60h): anxiety, w/d, muscle relaxant
lor: intermediate (10-18h): insomnia, anxiety, muscle relaxant
midaz: ultra short (2-5h): pre-anesthetic med

Question 7

zolpidem/zalepion/eszopiclone MOA

Answer 7

-act on same benzodiazepine binding site to increase GABA effect by increasing Cl- influx and freq of GABA receptor opening
plasma level peak: 1-2 hr; half life: 1.5-3h
metabolized by CYP3A4 like benzos and partially by hepatic aldehyde oxidase to form inactive metabolites

Question 8

pentobarb/phenobarb MOA

Answer 8

binds to GABA-A receptors on beta subunit in reticular formation and cortex, depress neuronal activity leading to sedative-hypnotic function, increase open time of GABAR in presence of GABA, at high concentrations, can also act as GABA mimetic
-very habit forming

Question 9

phenobarb onset/half life/use

Answer 9

long (1-3h); long (80-120h) anticonvulsant

Question 10

pentobarb onset/half life/use

Answer 10

short-intermediate (0.5-1h); intermediate (15-50h); preoperative sedation

Question 11

barbituates metabolism

Answer 11

-oxidation by CYPs forming alcohols, acids, ketones (appear in urine as glucuronide conjugates)
-induce activity or expression of many CYPs
(why need high doses, increase own metabolism)

Question 12

why do barbituates cause tolerance

Answer 12

-induction of CYP enzymes; causes cross-tolerance to general CNS depressants (benzos, ETOH)

Question 13

w/d symptoms benzos vs barbs

Answer 13

benzo mild: anxiety, insomnia, irritability, bad dreams, tremors, anorexia
barb mild: anxiety, insomnia, dizziness, nausea

barb severe: vomit, hyperthermia, tremors, delirium, convulsions, death
barb severe: agitation, depression, panic, paranoia, twitches, convulsions

Question 14

toxic dose of benzos vs. therapeutic

Answer 14

resp depression at 10x hypnotic dose

Question 15

propranolol

Answer 15

beta-blocker, blocks effects of the hormone epinephrine
-HR slows, BP drops, decreased sweating/shaking
used for situation anxiety (stage fright=fast acting)

Question 16

buspirone

Answer 16

partial agonist for the serotonin (5HT1A) receptor
MOA unclear, may increase dopa release in medial prefrontal cortex, striatum, hippocampus
produces only anxiolytic effects, no CNS depression
-no dependence, no rebound anxiety or w/e, no additive depression with ethanol
onset: 1-3 weeks