Others Sleep Meds

Question 1

Ramelteon

Answer 1

Melatonin Receptor Agonists

MOA:
-agonist at MT1 and MT2 melatonin receptors
—MT1 - regulation of sleepiness
—MT2 - regulation of circadian rhythm

Use:
-Sleep-onset insomnia

**Less efficacious than BDZ and Z compounds. ONLY APPROVED SEDATIVE-HYPNOTIC DRUG THAT IS NTO A SCHEDULED SUBSTANCE!!

Question 2

Suvorexant

Answer 2

Orexin Receptor Antagonist

MOA:
-Antagonist at OX1 and OX2 orexin receptors

Use:
-Sleep-onset insomnia
Sleep Maintenance insomnia

AEs:
-Daytime sedation, Impaired driving, Substance use disorder

Question 3

Phenobarbital

Answer 3

Barbiturates (problematic sedative-hypnotic)

MOA:
-Bind to allosteric site on GABAA receptors
-Increased affinity of GABAA receptor for GABA
-Potentiation of GABAergic inhibition of neuronal activity

Use:
-Insomnia
-Seizure disorders

Treatment Principles:
-Supplanted by BDZs, novel BDZ receptor agonists
-Many problems: tolerance, physical dependence, high addition potential, low therapeutic index, induction of CYP enzymes, long half-life
—*Many properties are far from those of an “ideal” hypnotic

Question 4

Diphenhydramine, Doxylamine

Answer 4

1st-generation Antihistamine (problematic sedative-hypnotic)

MOA:
-antagonist at H1 receptor

Use:
Insomnia

AEs:
-Significant daytime sedation (t1/2 = 9-10hours)
-Anticholinergic effects

*1st-gen H1 antihistamines block mAChRs as an off-target” effect

Question 5

Target and Clinical Pearls of Drugs that Promote Sleep

Answer 5

BDZ
Target: GABAA receptor
Pearls:
-“class effect”, with difference in PK properties
-may AEs: drowsiness, confusion, anterograde amnesia, psychomotor impairment, substance use disorder (C-IV)
-Many other indications: anxiety, spasticity

Z-Compounds
Target: GABAA receptor
Pearls:
-Fewer deleterious effects on sleep cycle than BDZs
-Less (but not zero!) psychomotor impairment, anterograde amnesia, tolerance, etc

Melatonin Receptor Agonist
Target: Melatonin Receptor
Pearls:
-Less efficacious than BDZs and novel BDZ receptor agonists

Orexin Receptor Antagonists
Target: Orexin Receptor
Pearls:
-New drug class
-Advantages over BDZs and novel BDZ receptor agonists unclear

Antihistamines
Target: H1 receptor
Pearls:
-1st-generation: daytime sedation, anticholinergic effects