032415 anti-anxiety agents Flashcards
slow wave sleep has what neurotransmitter involved
serotonin
REM sleep has what neurotransmitter involved
NE
tx of anxiety and insomnia
- benzodiazepines and related drugs (most commonly used)
- SSRIs (commonly used for anxiety)
- buspirone
- classical antihistamines
- alcohol, cannabis, opiates
- barbiturates
GABA localization
substantia nigra globus pallidus hippocampus limbic structures-amygdala hypothalamus spinal cord
GABA receptor
Cl ion channel that when Cl enters, hyperpolarizes neuron and makes it less likely to fire
benzodiazepines’ MOA
binds alpha subunit of the Cl channel. enhances GABA’s actions at the GABA receptor (causes more hyperpolarization per amt of GABA)
flumazenil
blocks action of benzodiazepines at the GABA receptor
used for overdoses of benzos, or for waking up from surgery
buspirone’s MOA
partial agonist of 5HT1A-inhibits adenylate cyclase and opens K channel
also binds dopamine receptors
alprazolam vs diazepam vs buspirone
alprazolam and diazepam depress the CNS and create dependence. they are both BDZ. alprazolam is short duration. diazepam is long duration.
buspirone produces little sedation and has no dependence. it has delayed onset
role of lipophilicity of benzodiazepines
diazepam has high lipid solubility-so rapid absorption into brain–has FAST onset of action.
lorazepam is less lipid soluble than diazepam, so absorption is slower. it has a longer duration of action after a single dose.
lipophilicity determines quick vs slow onset
metabolism of benzodiazepines
chlordizepoxide, DIAZEPAM, prazepam, chlorzepate get converted to desmethyldiazepam, which is an active metabolite and has LONG HALF LIFE.
OXAZEPAM, LORAZEPAM, alprazolam and triazolam don’t have active metabolites
CNS effects of BDZ
decreased anxiety sedation hypnosis muscle relaxation anterograde amnesia (IV)-dental work, colonoscopy anticonvulsant minimal CV and respiratory actions
drug interactions of BDZ
additive CNS depressionw most other depressant drugs (alcohol, etc)
drugs that affect hepatic metabolism like cimetidine
drug of choice for sleep disorders
BDZ
BDZ used for alcohol withdrawal
chlordiazepoxide
BDZ used for manic episodes
clonazepam (no EPS)
benzodiazepine withdrawal
(when BDZ used at high doses for long period, creates tolerance and dependence)
anxiety, insomnia, irritability, headache, hyperacusis, hallucianations, seizures
how to tx BDZ abuse
gradual dose reduction, or switch to longer acting drugs
buspirone does not potentiate other sedative-hypnotics and depressants: true or false
true
performance anxiety-what can you tx with?
beta blockers
effects of BDZ on sleep
decreased latency to sleep (good for insomnia) increased stage 1, 2 sleep decreased stage 3, 4 sleep decreased REM sleep rebound insomnia upon withdrawal
adverse effects of BDZ
daytime sedation ataxia rebound insomnia tolerance and dependence occasional excitement and stimulation increased death rate?
zolpidem and zaleplon MOA
NON-benzodiazepines chemically
bind to benzodiazepine receptor on GABA receptor complex
eszopiclone MOA
similar to zolpidem and zaleplon
ramelteon
melatonin MT1 and MT2 receptor agonist
barbiturates’ MOA
act also on GABA receptor
barbiturates’ side effects
respiratory depression
CV effects-if high doses, can produce sustained decreased in MAP and pulse pressure
chloral hydrate
aldehyde hydrate with pungent taste
pharm is similar to barbiturates
less effects on stages of sleep than BDZ and barbiturates
baclofen MOA
GABA mimetic agent that works at GABA B receptors, resulting in hyperpolarization and causing presynaptic inhibition. can result in decreased release of glutamate
tizanidine
alpha2 adrenergic agonist related to clonidine
may enhance both presynpatic and postynpatic inhibition
