Other Sedatives Flashcards
Describe H1 histamine antagonists
Diphenhydramine, doxylamine, hydroxyzine
Anticholinergic actions
Mild insomnia
Tolerance but no dependence or abuse
Describe melatonin
Hormone synthesized in the pineal gland
Controls circadian, seasonal, and reproductive rhythms
Normally released prior to induction of sleep
Decreases sleep latency, increases sedation
Resets clock in jet-lag, late-shift workers, elderly
Very few side effects, available OTC
Describe Ramelteon
MT1 and MT2 receptor agonist (melatonin receptors)
Similar efficacy as melatonin but product quality better regulated
Describe suvorexant
Hypocretin/orexin antagonist
Approved for insomnia in August 2014
Describe GHB
Naturally occurring fatty acid
Synthesized, stored, released like a NT
Metabolized from GABA
high affinity, NA dependent transporter specific for GHB
Highest in hippocampus, basal ganglia, and hypothalamus
Activates GHB receptor
—G-protein coupled to IP3 and DAG production
—Selective antagonists
High doses activate GABA-B receptor
What are GHB CNS effects
Sedation
Catalepsy - decrease nigrostriatal dopamine release
Euphoria - increase mesolimbic dopamine at higher doses
Increase growth hormone release
What is the therapeutic use of GHB
Approved to treat narcolepsy
Decreases sleep latency, increases sleep time
Does not disrupt sleep cycles
Alleviates daytime drowsiness
Some tolerance after repeated high dose use
No evidence of dependence
What are side effects of GHB?
Dizziness, mental clouding
Abuse liability increased by ethanol and other sedatives
Overdose usually in association with other drug use
Describe Pre-Gabalin and Gabapentin
Structural analogs of GABA
No activity at any GABA receptors or transporters
Anticonvulsants, relieves neuropic pain/fibromyalgia
Blocks VGCC - decreases pain neurotransmission
Some sedative side effect
Off label use for depression, mania, anxiety, insomnia
Describe cyclobenzaprine
Used for skeletal spasms, fibromyalgia
Describe metaxalone
Used as a muscle relaxant, MOA unknown
Describe carisprodol
Prodrug of meprobamate
Describe ketamine
Inhibits NMDA receptor, binds phencyclidine site
Dissociative anesthetic - no complete loss of conciousness
Clinically used as general anesthetic IV
Increases BP
No respiratory effect
Less sensory distortion/euphoria than phencyclidine
Some dysphoria during recovery, less in children
Low doses abused with ethanol as a sedative
What are treatment options for nicotine?
Nicotine itself
Nicotine antagonists/partial agonists - mecamylamine, varenicline
Clinidine - offsets adrenergic stimulation during w/d
Bupropion - DA and NE uptake inhibitor
Gamma-vinyl GABA - irreversible inhibitor of GABA-T
What are treatment options for stimulant addiction?
Cold turkey
Substitution detoxification - bupropion
Gamma-vinyl GABA, baclofen, other GABA B agonists
