A.26. Non benzodiazepine anxiolytics and non-benzodiazepine hypnotics. Pharmacotherapy of anxiety disorders.

Question 1

mechanism of action of Barbiturates

Answer 1

1. prolong GABA activity
2. ↑ duration of Cl⁻ channel opening–> hyperpolarization
3. at high doses–> GABA mimetic activity
4. at high doses–> irreversible cellular damage

Question 2

what is Thiopental?

Answer 2

ultra-short acting barbiturate

Question 3

what kind of CNS curve does barbiturates have?

Answer 3

linear

Question 4

what kind of CNS curve does benzodiazepines have?

Answer 4

plateau

Question 5

what are Secobarbital and Pentobarbital?

Answer 5

short-acting- barbiturates

Question 6

what is phenobarbital?

Answer 6

long-acting barbiturate

Question 7

how is phenobarbital excreted from the body?

Answer 7

unchanged in the urine

Question 8

what is phenobarbital used for?

Answer 8

seizures (not 1st line agent)

Question 9

what is thiopental used for?

Answer 9

anesthesia (IV)

Question 10

what are short-acting barbiturates (secobarbital) used for?

Answer 10

sleep disorders, insomnia

sedation

Question 11

adverse effects of barbiturates

Answer 11

CNS depression (additive effect)

Question 12

in what case are barbiturates contraindicated?

Answer 12

patients with porphyria

*they induce excessive heme synthesis

Question 13

barbiturates are potent inducers of…?

Answer 13

CYP450 enzymes

*enhances metabolism of oral contraceptives, warfarin, statin

Question 14

list the non-BZ’s sedative-hypnotic drugs

Answer 14

Zaleplon
Zolpidem 
Buspirone 
Melatonin
Ramelteon

Question 15

what is the indication for Buspirone?

Answer 15

generalized anxiety disorders

“I get anxious if the bus doesn’t arrive at one, so I take buspirone”

Question 16

what are the side effects of buspirone

Answer 16

GI distress
Tachycardia
Paraesthesia (abnormal sensation of the skin)

Question 17

what are the non-BZ’s given for sleep disorders (sleep-onset insomnia)?

Answer 17

Zaleplon
Zolpidem
“these ZZZ’s put you to sleep”

melatonin (OTC)
Ramelteon

Question 18

how are non-BZ’s given?

Answer 18

orally

Question 19

which non-BZ’s have short duration?

Answer 19

buspirone
zaleplon
zolpidem

Question 20

what type of metabolism do non-BZ’s have?

Answer 20

hepatic P450 metabolism

Question 21

what are Zaleplon, Zolpidem and Eszopiclone?

Answer 21

GABAᴀ agonists

Question 22

what is the difference between BZ’s and Zaleplon?

Answer 22

Zaleplon doesn’t produce the anxiolytic, muscle relaxant, or anticonvulsant effect associated with BZ’s

Question 23

side effects of Zolpidem and Zaleplon

Answer 23

CNS depression (additive with other CNS depressants)
dependence liability

Question 24

how long does the clinical effect of Buspirone take?

Answer 24

1-2 weeks

Question 25

what is Buspirone?

Answer 25

5-HT₁ᴀ partial agonist

Question 26

what does Melatonin do?

Answer 26

regulates the sleep-wake cycle

Question 27

what does Ramelteon do?

Answer 27

activates MT₁ and MT₂ receptors in the suprachiasmatic nucleus

Question 28

what are the SE of Ramelteon?

Answer 28

Dizziness, fatigue
endocrine changes (↓ testosterone, ↑ prolactin)

Question 29

what is Flumazenil and what does it do?

Answer 29

it’s an antagonist at BZ’s sites on GABAᴀ receptor

Question 30

how is Flumazenil given?

Answer 30

IV

Question 31

what T1/2 does flumazenil have?

Answer 31

short

Question 32

when do we give Flumazenil?

Answer 32

1. benzodiazepine overdose
2. to reverse anesthesia
3. terminating the activity of Zolpidem, zaleplon and eszopiclone

Question 33

what can’t Flumzenil reverse?

Answer 33

CNS effects caused by barbiturates and alcohols