Anxiolytics and hypnotics

Question 1

Name the benzodiazepines

Answer 1

Alprazolam, clonazepam, diazepam, lorazepam, midazolam, ozaxepam.

The “zepam” drugs.

Question 2

What is the MOA of benzodiazepines?

Answer 2

GABA-A enhancement

Question 3

Benzodiazepines: Indications?

Answer 3

Anxiety disorder;
panic disorder;
insomnia (shortterm);
preanesthetic;
status
epilepticus
(anticonvulsant);
Alcohol
Withdrawal

Question 4

Benzodiazepines: Side effects?

Answer 4

Common:
drowsiness,
memory
impairment,
reduced motor
coordination,
somnolence

Severe: potential for
addiction/abuse,
respiratory
depression,
teratogen (cleft lip),
neonatal
toxicity/withdrawal

Question 5

Benzodiazepines: Metabolism?

Answer 5

Rapidly absorbed from gut and metabolized by liver.

Question 6

Which benzodiazepines require glucuronide conjugation (not hepatic oxidation)?

Answer 6

Lorazepam, oxazepam, and temazepam (LOT)

Question 7

Which benzodiazepines are preferred agents for elderly or those with liver impairments? Why?

Answer 7

Lorazepam, oxazepam, and temazepam (LOT)

Why?
No active metabolites, and are generally shorter-acting.

Question 8

Which benzodiazepines have shorter half-life and high potency?

Answer 8

Alprazolam, lorazepam,
midazolam, oxazepam, temazepam

LOT + MA

Question 9

Which benzodiazepines have longer half-life and lower potency?

Answer 9

Clonazepam, diazepam.

CD!

Question 10

What are contraindications of benzodiazepines?

Answer 10

acute narrow-angle glaucoma,

respiratory insufficiency, sleep apnea

Question 11

What are precautions that should be taken for people on benzodiazepines?

Answer 11

abrupt discontinuation → withdrawal, active or
history of alcohol abuse → addiction, co-administration with
other CNS depressants → respiratory depression

Question 12

Flumazenil: MOA

Answer 12

Potent benzodiazepine R antagonist;
competitively inhibits benzodiazepine
recog site on GABA/benzodiazepine R complex, reversing benzodiazepine effects on CNS. Used for benzodiazepine overdose or toxicity.

Question 13

Flumazenil: Side effects

Answer 13

Carries risk of
precipitating an
abrupt
benzodiazepine
withdrawal (can
lead to seizures).

Question 14

Buspirone: MOA

Answer 14

Serotonin (5-HT1A) R partial

agonist.

Question 15

Buspirone: Indications

Answer 15

Indicated for generalized
anxiety disorder; chronic anxiety
(especially in patients with active or history of substance abuse).

Question 16

Can buspirone be used for acute anxiety?

Answer 16

INEFFECTIVE in treating acute

anxiety (i.e., not prescribed p.r.n.).

Question 17

Buspirone: Side effects

Answer 17

Dizziness,
drowsiness,
headaches

Question 18

Buspirone: Metabolism

Answer 18

Hepatic metabolism; oral absorption

Half-life = 2-11 hours (admin BID)

Question 19

Non-benzodiazepine hypnotics: Are they safer than benzodiazepines?

Answer 19

Non-benzodiazepine hypnotics offer advantages over benzodiazepines in terms of safety (less
tolerance/dependence) and have largely replaced benzodiazepines as hypnotic medicines.

However, they lack the anxiolytic,
anticonvulsant, and muscle-relaxant
properties that benzodiazepines offer.

Question 20

Difference between hypnotics and sedatives?

Answer 20

A sedative lowers excitement and calms the awake patient, whereas a hypnotic
produces drowsiness and promotes sleep

Question 21

What are the non-benzodiazepine hypnotics?

Answer 21

Zolpidem, zaleplon, eszopiclone.

Question 22

Non-benzodiazepines: MOA

Answer 22

Benzodiazepine R agonists,
bind to GABA receptors subtypes
that specifically modulate sleep →
less unwanted SE’s

Question 23

Non-benzodiazepines: Indications

Answer 23

Short term (<4
weeks) treatment of insomnia
a. Sleep onset insomnia: zolpidem
and zaleplon
b. Sleep onset and sleep maintenance
insomnia: zolpidem ER and
eszopiclone

Question 24

Non-benzodiazepines: Side effects

Answer 24

Shorter duration of
action than most
benzodiazepines
and therefore less
likely to cause next day
sedation.
However,
drowsiness,
dizziness,
unsteady gait,
rebound insomnia,
and memory
impairment have
been reported.
Potential for
abuse/addition, but
more of a concern in
patients who already
suffer from
addiction.

Question 25

Non-benzodiazepines: Metabolism

Answer 25

a. Metabolized by the p450 system and are therefore affected
by inducers/inhibitors of this system.
b. Drugs do not significantly induce/inhibit enzymes themselves.

Question 26

Melatonin receptor agonist?

Answer 26

Ramelteon

Question 27

Ramelteon: MOA

Answer 27

M1 and M2 melatonin R agonists in
the suprachiasmatic nucleus of the
hypothalamus.

Question 28

Ramelteon: Indications

Answer 28

sleep onset insomnia

Question 29

Ramelteon: Side Effects

Answer 29

Headache, dizziness, drowsiness, fatigue, nausea. Ramelteon is the only FDA-approved
drug for insomnia that is not a controlled substance because it has not been
associated with abuse or withdrawal.

Question 30

What are other drugs used in clinical practice to treat insomnia?

Answer 30

Sedating antidepressants (tricyclics, trazodone, and
mirtazapine); antihistamines (diphenhydramine); and benzodiazepines (temazepam). The choice of which hypnotic to use is largely based on side
effects, comorbidities, and patient preference.