lecture 60 Flashcards
yang - pathophysiology of anxiety/sleep disorders
what is the defintion of hypnotic?
induces sleep
implies restful, refreshing sleep
not hypnotized
natural sleep
what does anxiolytic mean?
antianxiety
relieves anxiety without sleep or sedation
what is the reticular formation?
extends through the central core of the medulla oblongata, pons, and midbrain
intricate system composed of loosely clustered neurons in what is otherwise white matter
what are the stages of sleep?
wakefulness
NREM (1, 2,3,4) slow-wave sleep
REM sleep
what do each of the NREM sleep stages correlate to?
stage 1 - dozing
stage 2 - unequivocal sleep
stage 3 - voltage increase, frequency decrease
stage 4 - delta waves
what are the factors that regulate sleep?
age
sleep hx
drug ingestion (acute and withdrawal produce rebound effects)
circadian rhythms
what NTs are biological regulators of sleep?
catecholamines (epi, NE, DA)
serotonin
histamine
ACh
adeosine
GABA – main target for current meds
what neuromodulators are biological regulators of sleep?
growth hormone
prolactin
cortisol
melatonin – hormone of darkness
endogenous peptides
what does the GABAa receptor and chloride ion channel complex have in sleep?
targets for sedative hypnotics
allosteric sites for benzos, barbiturates, ethanol, and glucocorticoids
how do benzos affect GABA?
facilitate GABA action thus increasing frequency of channel opening
require intact GABA system
where do z-hypnotics act?
on the BZ1 receptors of a1
what is MOA of flumazenil?
BZD antagonist used in benzo overdose treatment
how do barbiturates modulate the GABAa receptor?
increases duration of channel opening and leads to direct effects on GABAa in high doses
what does the 1 position in benzos induce?
alkylation
source of active metabolites
how does the SAR of 1-2 bond affect benzos?
annealating the 1-2 bond with an electron rich ring (Triazole or imidazole) yields high affinity and decreased half life
what can diazepam be used to treat?
convulsive disorders (seizures)
accumulation of metabolites
what are the main drugs according to their pharmacokinetics?
slow (active metabolites) – diazepam
intermediate – clonazepam
rapid – midazolam
how do benzos mainly affect properties?
decreases REM
decreases stage 3 and 4
anticonvulsant activity
what are the SE of benzos?
dose dependent
sedation –> confusion, ataxia, daytime sedation with longer acting agents (tolerance develops)
weakness, HA, vertigo, N, paradoxical effects
what are precautions and interactions of benzos?
other sedatives, alcohol
pregnancy and breast-feeding
what are the drug dependent and abuse of benzos?
abuse potential
small kick - often when in combo
which of the z-hypnotics is for short-term vs long-term use?
zlopidem, zaleplon – short term
eszopiclone – long term
what are the SE of z-hypnotics?
less negative effects on sleep patterns compared to benzos
sleep-driving, sleep-cooking, sleep-eating, sleep-sex (FDA: warn your patients)
what main barbiturates match with what classification?
long acting - anticonvulsant - phenobarbital
short-intermediate acting - sedative-hypnotics - pentobarbital
ultra-short acting - IV anesthetics
what is an important consideration of barbiturates?
respiratory death –> death
