Sedative, hypnotics, anxiolytivs Dr.Yang Flashcards
Sedative
calms anxiety, decrease excitement and activity, dose not produce drowsiness, or impair performance
Anxiolytic
antianxiety, releives anxiety without sleep or sedation
Hypnotic
induces sleep
narcotic
now refers to opioids or illegal drugs
Reticular formation
Extends through the central core of the medulla oblongata, pons, and midbrain
composed of loosely clustered neurons in what is otherwise white matter
contains dopamine, adrenergic, serotonergic, and cholinergic neurons. regulates sleep-wake transition and synchronization of EEG
Stages of sleep
wakefulness, non rapid eye movement, rapid eye movement
NREM
stage 1 - dozing
stage 2 - unequivocal sleep
stage 3 - voltage increase, frequency decrease
stage 4 - delta wave
REM sleep (similar to awake in EEG)
SLEEP DEPRIVATION - TOTAL SLEEP, DELTA SLEEP, REM
Factors that regulate sleep
Age, sleep history, drug ingestion, circadian rhythms
Biological regulators of sleep
Neurotransmitters: catecholaines, serotonin, histamine, achetylcholine, adenosine, GABA
Neuromodulators: growth hormone, prolactin, cortisol, melatonin, enndogenous peptides
GABAergic neurotransmission
GABAa receptors
GABAb receptors
GABA transporters
GABA-T (transaminase)
GABAa receptor/ chloride ion channel complex
Targets for sedative-hypnotics
Orthosteric site: GABA
Allosteric site: benzodiazepine (BZD) side (alpha1 and gamma2), Barbiturate, ethanol, glucocorticoid
Channel pore: picrotoxin
Ligands acting at the BZD receptor
Benzodiazepines: facilitate GABA action (alpha 1-5) increase frequency, require intact gaba system
Non-benzodiazepines: solpidem (ambien), Zaleplon (sonata, Esczopiclone (lunesta) - BZ1 receptors of alpha 1
BZD: antagonists: flumazenil (romazicon)
inverse BZD agonists: B carbolines
Ligands acting on other non-orthosteric sites
BZDs: increase frequency of channel opening
Barbiturtates: increase duration of channel opening and direct effects on GABAa
Alcohol: enhances action of GABA at GABAa receptor
Benzodiazepines Chemistry and metabolism
- special structure : 1 position alkylation provides active metabolites
annealating the 1-2 bond with an electron rich rish (triazole or imidazole) yields high affinity and decreases half life
Slow elimination rate
Diazepam (valium) - treatment of convulsive disorders, accumulation of metabolies
Chloridazepoxide (librium) - 1st benzo used for alcohol withdrawal
Flurazepam (dalmane) - used as a hypnotic
Clorazepate (tranxene) - alcohol withdrawal, convulsive disorders, accumulation of metabolites
Quazepam (doral) - hynotic
prazepam - not available in US
Intermediate elimination rates
Clonazepam (Klonopin)- used as an anticonvulsant
alprazolam (Xanax) - withdrawal symptoms can present if abrupt d/c
lorazepam (ativan) - used as an anxiolytic and as a hypnotic
oxazepam (serax) - used as an anxiolytic and for alcohol withdrawl
temazepam (restoril) - used as a short term hypnotic
rapid elimination rates
Midazolam (versed) - rapid anesthesia
Triazolam (halcion, d/c) - used as a short term hypnotic
Benzodiazepines usage
Slow elimination: active metabolies, accumulation, drowsiness and sedation, useful in patients who wake up
intermediate to rapid elimination: preferable in patients with hepatic problems, preferable in elderly patients, drugs that alter liver enzymes, rapid tolerance, rebound insomnia
General considerations
Readily absorbed (can delay with food)
Have active metabolites or are converted to active forms
Increased lipid solubility will increase speed of delivery to brain
redistribution to highly perfused tissue may decrease duration of action
cross placental barrier and are detected in breast milk
extensive protein binding, but not clinically significant
Dose response curves for denzos vd barbiturates
Barbiturates are dangerous because by increasing duration of gaba receptor it can cause coma if dose is too high it can put people into a coma
benzos increase frequency of receptor, so increasing dose will not lead to coma
Benzodiazepines use
not as commonly used for sleep aid due to its possibilities to Decrease rem sleep and Decrease stage 3 and 4 which can make you drowsy throughout the day
more used for Anticonvulsant activity
Side effects of benzos
Dose dependant
sedation, weakness, headache, vertigo, nausea, paradoxical effects
Precautions and interactions with benzos
Other sedatives, alcohol
pregnancy and breast feeding
Flumazenil (romazicon)
Benzodiazepine antagonist
used for benzo overdose
initial dose - 0.2mg IV / 30sec
max dose - 3mg
SE: induce convulsions, panic attacks, agitation, confusion, nausea and vomiting, headache
Non-benzodiazepines
Act at BZD binding site
zolpidem (ambien)
short term treatment of insomnia
Zaleplon (sonata) - short term treatment of insomnia
Eszopiclone (lunesta) - long term use of insomnia
SE: daytime drowsiness, dizziness, ataxia, nausea, and vomiting, causes less negative effects on sleep patterns, warn your patients about sleep driving, sleep cooking, sleep eating, sleep sex
Long acting barbiturates
Phenobarbital (luminal) - anticonvulsants
Short to intermediate acting barbituates
Phetobarbital (nembutal), amobarbital (amytal)- used for sedative -hypnotics
Ultra short acting barbiturates
IV anesthetics
Thiopental
methohexital
thiamylal
SE: respiratory depression
Comparing BBT, BZD, and Z-hypnotics
BBT: bint to all GABAa alpha1-5 increase duration, and direct effects on GABA
Benzo: bind to all GABAa alpha1-5 increase frequency of GABA channel
Z-hypnotics: bind to GABAa BZ1 receptors of alpha1 increase frequency of GABA channel opening
*Flumazenil is used for over dose of benzo but not for barbiturates
