Neuroanatomy-Hypnotic Drugs Flashcards
SSRIs and SNRIs
First line treatment for most anxiety disorders as well as used as first line here. Not necessarily sedatives as the rest of these will be.
Barbituates
Decrease in:
- sleep latency (time it takes to get to sleep)
- REM sleep
Tolerance to sleep facilitation within 2 weeks.
Discontinuation- REBOUND REM Sleep, Psychological Dependence
Mechanisms:
-Act at GABAA Receptor (Hyperpolarizes)
- Barbituates bind at Alpha-Gamma in the transmembrane segment. Keeps channel open longer. Bind at same place as general anestetic.
- DO NOT need GABA to bind -> can lead to death if too much is given.
- Well absorbed
- Lipophilicity, acidosis- CNS entry
- Termination by redistribution and Renal excretion.
3 Categories of Barbiturates:
-long-acting (t ½ > 50 hrs) (e.g. phenobarbital)
- short to intermediate acting (<50 hrs)(e.g. secobarbital)
- ultrashort acting (< 10 hrs) (e.g. thiopental)
CNS Effects:
- Sedation
- Hypnosis
- Cognitive Impairment
- Anesthesia (Laryngospasm)
- Respiratory Depression
- Death
CV Effects:
Slight decrease in blood pressure
Depression of vasomotor centers
at toxic doses – > circulatory
collapse
Hepatic Effects:
- Induction of P450 Enzymes
(enhance Metabolism of other
drugs) - Enhanced Metabolism of Barb-
iturates and all drugs metabolized
by P450 Enzymes
Poisoning: Don’t give CNS stimulants!
Benzodiazapines
Have basically replaced Barbituates due to possiblity of death in barbs because they can activate GABA.
Advantages: Safer- higher therapeutic index, Tolerance- lower, Addictive liability- lower, Less drug interactions
Increase frequency of opening of GABA receptor but NOT and agonist.
Decrease in:
- sleep latency (time it takes to get to sleep)
- REM sleep (less than Barbs)
- Sleep stages 3 and 4
Uses:
-Anxiety- w/ or w/o Depression
-Hypnosis
-Panic Disorders
-Spasticity (muscle relaxant)
-Premedication for Surgery
-Alcohol Withdrawal (same receptor as alcohol)
-Adjunct in disorders where
anxiety may worsen condition
Tolerance to sleep facilitation within 4-6 weeks.
Discontinuation- REBOUND REM Sleep, Psychological Dependence
Mechanisms:
-Act at GABAA Receptor (Hyperpolarizes)
- Benzos attach at the alpha-gamma site. Analogous to agonist site, but tweeks the receptor to help the GABA. It’s a partial agonist, but GABA is needed. SO, increases frequency of open.
- Note parent compound AND metabolite might be active.
Categories:
- Ultra- short acting (t ½ < 2 hrs)
- Short acting (t ½ < 6 hrs) - don’t last the whole sleep cycle, can cause anxiety, rebound insomnia.
- Intermediate Acting ( 6-24 hrs)
- Long Acting (> 24 hrs)
Side Effects:
- Mostly Psychomotor and Cognitive, More apparent in the elderly
Flumazenil
Benzodiazepine Antagonist
- No activity in its own right
- Reverse the effects of ingested or administered BDZ agonists only
- Ineffective for most other sedatives
Zolpidem (Ambien)
Structurally not a benzodiazepine, but binds to same site on GABA-A Receptor as benzodiazepines (Only bind to GABA-Ar = sleep related only. So not effective as anti-depressant).
-Good hypnotic, with less effects on stages of sleep
-Low incidence of rebound insomnia,
daytime sedation
Zaleplon (Sonata)
Structurally not a benzodiazepine, but binds to same site on GABA-A Receptor as benzodiazepines (Only bind to GABA-Ar = sleep related only. So not effective as anti-depressant).
- Good hypnotic, with less effects on stages of sleep
- Low incidence of rebound insomnia, daytime sedation
- Short half-life ~ 1 hour
Eszopicline (Lunesta)
Structurally not a benzodiazepine, but binds to same site on GABA-A Receptor as benzodiazepines (Only bind to GABA-Ar = sleep related only. So not effective as anti-depressant).
- Good hypnotic, with less effects on stages of sleep
- Low incidence of rebound insomnia, daytime sedation
- Short half-life ~ 1 hour
Chloral Hydrate
Metabolized to trichloroethanol
- Short duration
- No enzyme induction
- Tolerance/Dependence, Withdrawal can be severe
Buspirone
- Atypical Anxiolytic
- NOT A HYPNOTIC
- Not a GABAA-R drug
- Acts at 5-HT1A and DA-2 receptor
- Cannot substitute for a BDZ
- Does not produce tolerance and physical dependence
Not that effective as an antyolitic.
Ramelteon (ram el’ tee on)
- Hypnotic
- Not a GABAA-R drug
- Not a controlled substance
- Agonist for melatonin MT1receptor
- which promotes onset of sleep
- Does not produce tolerance and physical dependence
- Well tolerated, nausea/vomiting
Good drug. Strongly recommends we try this one first!
Meprobamate
RARELY if ever used.
Similar to Barbs.
Beta- Blockers
useful in alleviating performance anxiety.
Baclofen
Muscle Relaxant.
GABA-B receptor drug:
- inhibitory at cord and brain
- Antispasmodic useful in treatment of multiple sclerosis or spinal injury
Not an Anxiolytic
Few side effects
Dantrolene
Muscle Relaxant
-reduces spasticity
-interferes with Ca2+ release in
skeletal muscle
useful in malignant hyperthermia due to general anesthetics
