Non benzodiazepine hypnotics

Question 1

Name the non-Benzodiazepine hypnotics

(“catching some Z’s”)

Answer 1

the 3 Z’s

Zolpidem
Zaleplon
esZopiclone

Question 2

non-Benzodiazepine hypnotics MOA

Answer 2

-bind same allosteric site as Benzodiazepines at GABA-A receptor
(“ben’s diner coworker and zzz mattresses coworker are grabbing the same Cab-A handle”)

-GABA-A receptor is a chloride channel,chloride influx hyperpolarizesnerve cells
(“chlo-rider” sign on Cab-A)

-potentiates (enhance) transmission of GABA in CNS
(“Red CNS light on Cab-A”)

-GABA is the major inhibitory neurotransmitter in the CNS (the sign on Cab-A says “take it easy” )

-Barbiturates bind different allosteric site on GABA-A receptors
(“barber shop located on other side of Cab-A”)

-alcohol also binds GABA-A receptor but on a different allosteric site
(“alcoholic guy is on back of Cab-A”)

Question 3

Pharmakokinetics of Zolpidem Zaleplon es-Zopiclone

Answer 3

-Zolpidem and Zaleplon are fast acting non-Benzos with rapid onset (sheeps sign says :”fall asleep FAST”)

-Non-benzos hypnotics have short duration of action
(“sheeps quick jump and fall on sign”)

-Zolpidem and Zaleplon are metabolised by the liver
(“sheeps on sign have liver spot on them”)

Question 4

what are non-Benzodiazepene hypnotics used for ?

Answer 4

-useful in treatment of insomnia

• Zolpidem and Zaleplon are short-acting and therefore useful in treating Sleeep onset insomnia and not for maintaining sleep
• ​esZopiclone has longest half life and is therefore effective for both falling asleep and maintaining sleep

​-less likely to cause withdrawal symptoms
(“sale sign says break those bad sleeping habits”)

-non-benzos are less likely to cause tolerance
(sale sign says “returns not tolerated”)

Question 5

Side effects on non-Benzos

Answer 5

-elderly are more sensitive to the side effects

-can cause Central Ataxia
(“unbalanced stack of pillows”)

-avoid use with other CNS depressants
(“cannot combine with other CoupoNS”)

• e.g.- 1st Gen. Antihistamines
  (“bee swatter coworker hitting old fart”)

Question 6

how can you reverse non-benzos sedation ?

Answer 6

Flumazenil - BZD Competitive antagonist
(“fluffy muzzled dog biting on zzz matresses red arrow sign”)

Question 7

what other drugs can be used to treat insomnia ? MOA?

(“let your sleepless nights melt away”)

Answer 7

• *Melatonin**
• *Ramelteon/Agomelatin** (melatonin receptor agonists)

-MT1 and MT2 melatonin receptors are found in the suprachiasmatic nucleus of the hypothalamus and are activated by Ramelteon
(“nucleus above x shaped ceiling fan”)

• **-Ramelteon has no direct effects on GABA-ergic transmission in the CNS **
• melatonin receptors maintain the Circadian rythm (“light and dark spotlights”)

-Ramelteon/Melatonin have fewer side effects and are safer in Geriatric patients
(peacefully sleeping old fart below “melt-away sign”)