E1- Sedative-Hypnotics and Anxiolytics Flashcards
What is the major inhibitory neurotransmitter in the brain?
GABA
What is the general MOA of sedative-hypnotics/anxiolytics?
Bind to GABA, to either intensify or prolong the actions of GABA
What is an antihistamine used as an anti-anxiety medication that causes sedation that is a good option for recovering addicts and the elderly?
Hydroxyzine
What is the MOA of barbiturates?
Bind to GABA receptor to stimulate Cl- influx and produce inhibition independent of GABA (prolongs channel opening time)
What makes barbiturates a drug of abuse?
Causes euphorai
What long-acting barbiturate is used as an anticonvulsant?
Phenobarbital
Do barbiturates cross the BBB?
Yes, CNS depressant
How are barbiturates metabolized?
By the liver
Induce CYP450s
What are SE of barbiturates?
CNS depression
Paradoxical excitement
Severe physiological and psychological dependence
What are contraindications of barbiturates?
Porphyria
Pulmonary insufficiency
Combination with alcohol (supra-additive effects)
What is the safety margin of barbiturates?
Low margin of safety, no “ceiling effect”
How is barbiturate OD treated?
What should not be given?
Diuresis and alkalization of the urine
Stimulants increase mortality rate
What patient population should typically not be given benzodiazepines?
Elderly (do not metabolize BZs as quickly)
What benzodiazepines have a long duration of action?
Diazepam
Flurazepam
What benzodiazepines have an intermediate duration of action?
Alprazolam
Lorazepam
Oxazepam
What benzodiazepine has a short duration of action?
Midazolam
What is the MOA of benzodiazepines?
Bind to GABA receptor to increase the affinity of the receptor to GABA, prolonging its action; dependent on GABA
What is the safety margin of benzodiazepines?
High margin of safety, “ceiling effect”
What are the general uses of benzodiazepines?
Anxiety Insomnia Status epilepticus Sedation, amnesia, anesthesia Muscle relaxation
In what anxiety disorders are benzodiazepines not used?
Panic disorder, phobias, obsessive compulsive
PTSD, anxiety in children and adolescents
What benzodiazepines are used for insomnia?
Flurazepam
Temazepam
What benzodiazepines are used for Status Epilepticus?
Diazepam
Lorazepam
What benzodiazepines is used in preparation for anesthesia for short surgical procedures?
What is a SE?
Midazolam (IV)
Anterograde amnesia
What benzodiazepines are used for muscle relaxation?
Diazepam
What are SE of benzodiazepines?
CNS depression
Paradoxical excitement
Supra-additive with alcohol Sleep related behaviors Physical dependence may occur (high abuse potential)
What are contraindications of benzodiazepines?
Pregnancy
Sleep apnea
Elderly
Regarding BZs, what can cause rebound increases in insomnia and anxiety? How can this be avoided?
Abrupt discontinuation
Taper slowly
What is the MOA of Fluemazenil?
Benzodiazepine antagonist; competes with BZs for GABA receptor
What is the use of Fluemazenil? (2)
Hypoersomnia
Reverse the effects of BZs (Ex: Midazolam, which can sometimes cause respiratory depression)
What are SE of Fluemazenil?
Triggers withdrawal and seizures in pts who are physically dependent upon BZs
What is a contraindication of Fluemazenil?
Pts with hx of seizures
What the the “z-drugs?”
Zolpidem, Zaleplon, Eszopiclone
What is the MOA of the “z-drugs?”
Bind to the BZ1 subtype of the GABA receptor to increase GABA mediated inhibition
What class of sedative-hypnotics have no anxiolytic, anticonvulsant, or muscle relaxant properties?
The “z-drugs?”
What is the use of the “z-drugs?”
Insomnia
Do most “z-drugs” have a short or long duration of action?
Short duration of action (morning drowsiness is unlikely )
Which “z-drug” has a long half-life and can be used for long-term tx of insomnia?
Eszopiclone
What is the margin of safety for the “z-drugs?”
High margin of safety
What are SE of the “z-drugs?”
GI (diarrhea, nausea)
Drowsiness
Sleep related behaviors
Confusion, memory loss, and psychosis in elderly
Regarding the “z-drugs,” what can use rebound insomnia?
Rapid discontinuation
Abrupt cessation after long-term use of Eszopiclone can cause what?
Withdrawal sxs (CNS stimulation, anxiety, seizures)
What is the MOA of Suvorexant?
Orexin receptor antagonist
What is a possible drug interaction with Suvorexant?
Metabolized by CYP3A4 (Cimetidine inhibits CYP3A4)
What are SE of Suvorexant?
HA Abnormal dreams Sleep paralysis Hallucinations Worsening depression
What is a contraindication of Suvorexant?
Narcolepsy
What is the MOA of Ramelteon?
Melatonin analogue; resets sleep-wake cycle; promotes sleepiness with no GABA effect
What are SE of Ramelteon?
Drowsiness, dizziness, nausea
What is the use of Suvorexant?
Insomnia
What is the use of Ramelteon?
Insomnia
What is an antihistamine that can be used for occasional insomnia? (good option for addicts)
Diphenhydramine
What is the MOA of Chloral Hydrate?
Converted to trichloroethanol which causes sedation
What is the margin of safety of Chloral Hydrate?
Low margin of safety (high doses induce respiratory and vasomotor depression)
What can long-term use of Chloral Hydrate cause?
Liver damage and fatal intoxication
What are uses of Chloral Hydrate?
Sedation during pediatric dental procedures
cheap
What is the MOA of Buspirone?
Relieves anxiety without producing sedation; works independently of GABA at serotonin receptors
What class of anxiolytic has no muscle relaxant or anticonvulsant properties?
Buspirone
Why is Buspirone a good option for tx of anxiety in alcoholics/addicts?
Does not potentiate CNS depression with alcohol or BZs
What are uses of Buspirone? (6)
Generalized anxiety Anxiety with depression ADHD Autistic pts with anxiety PMS Anxiety in recovering alcoholics/addicts