Anti Anxiety Drugs and Hypnotics

Question 1

Define anxiolytic, sedative, hypnotic

Answer 1

anxiety reducer
inducer of calmness without drowsiness
inducer of normal sleep

these 3 treat symptoms, not disease

Question 2

What is the target of anxiolytics, sedatives, hypnotics?

Answer 2

GABA, the major inhibitory NT in CNS

Question 3

what are benzodiazepines and barbituates used for?

Answer 3

antianxiety and sedation / hypnosis respectively

Question 4

Name the longer duration benzodiazepines and for what are they used?

Answer 4

alprazolam
chlordiazepoxide
clonazepam
clorazepate
diazepam
lorazepam
oxazepam

These are primarily used to treat anxiety

(these are not bolded)

Question 5

Name the shorter duration benzos and their primary use

Answer 5

estazolam
flurazepam - hypnotic drug of choice
temazepam
triazolam
quazepam

shorter duration benzos are primarily used to treat insomnia

(these are not bolded)

Question 6

Midazolam is aka what? and is used for what?

Answer 6

versed, used in G.A. given IV

Question 7

Describe the behavioral mechanism of action of benzos

Answer 7

• low dose: decrease aggressiveness / anxiety
• higher doses: sedation and hypnosis, anesthesia, amnesia
• muscle relaxation: central and spinal cord mechanisms = antispastic agents

Question 8

describe the biochemical mechanism of action of benzos

Answer 8

activate benzo receptor sites in brain, these are located close to or on GABA receptor - they enhance the activity of GABA on its receptors

NOTE: benzos do not directly activate GABA, but rather increase sensitivity to endogenous signals

Question 9

comment on the pharmokinetics of benzos

Answer 9

absorbed from G.I. tract

metabolized in liver, do not induce P450

Question 10

comment on the potential issues associated with taking benzos

Answer 10

tolerance: given dose may lose efficacy
withdrawal: discomfort, seizures
habituation: psychological dependency

Question 11

describe side effects of benzos. do they have a low or high TI?

Answer 11

very high therapeutic index because of limited efficacy (enhancers, not activators)

• ataxia
• drowsiness
• impaired judgement
• confusion in the elderly
• decreased ability to learn new material
• can interact with CNS depressants (ethanol)
• usual disturbances: diplopia, nystagmus

Question 12

what doeth flamazenil?

Answer 12

benzo receptor blocker - typically used for benzo overdose

given IV because of 1st pass metab

Question 13

For what are non benzo hypnotics used?

and how do they act?

Answer 13

sleep

act by binding only to alpha subunits of benzo receptors - this has little effect on muscle relaxation or seizure activity

Question 14

name the 4 non benzo hypnotics and potential side effects

Answer 14

the three “z” drugs:

zolpidem (ambien)
zaleplon (sonata)
eszopiclone (lunesta)

and

dexmedetodimine

with any hypnotics, there may be behavioral changes:

• decreased inhibitions
• bizarre behaviors
• sleep-driving
• hallucinations

Question 15

how does dexmedetodimine work? SE?

Answer 15

alpha-2 agonist: induces sleep, sedation without resp. depression

SE: hypotension, bradycardia

recall: clonidine and alpha-methyl DOPA

Question 16

for what is buspirone used?

Answer 16

anxiety: partial serotonin (5HT) agonist

no sedative or hypnotic effects, slow onset, no interaction with benzodiazepines or ethanol

Question 17

Name the 5 barbituates “itals” discussed in class and their duration of action.

Answer 17

3-4 hours duration:
pentobarbital
secobarbital

6-8 hours duation:
amobarbital
butabarbital

10-16 hours duration
phenobarbital

Question 18

describe the mechanism and sites of action for barbituates

Answer 18

enhance action of GABA - 10x more efficacious than benzodiazepines

act on reticula activating system
sensory cortex: unconsciousness, not analgesic
medullary resp center: death due to resp. depression

Question 19

name use of barbituates other than hypnosis

Answer 19

epilepsy

Question 20

Name 3 issues commonly associated with barbituates

Answer 20

decreased respiration, TI=10 = used in suicide attempts
interactions with ethanol = synergistic CNS repression - can cause death

dependence - suppresses REM sleep - people who stop taking can have scary dreams!

Question 21

what is ramelteon? what is its mechanism of action? and SE?

Answer 21

• sleep inducer
• melatonin receptor agonist
• no effect on GABAergic pathways
• helps to maintain circadian sleep rhythms
• reduces time to sleep onset
• may improve sleep quality

Side effects:
somnolence - sleepiness / strong desire for sleep
fatigue
long term use: decreased Testosterone syn

has synergistic effects with alcohol

Question 22

name an OTC sleep inducer

Answer 22

diphenhydramine: antihistamine with strong hypnotic effects