sedatives BDZ hypnotics and anxiolytics
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- BDZ distribution, Absorption, Metabolism, Excretion
-
high lipid water partition coefficient, bind plasma proteins well, less than anticipated Vd
completely absorbed orally
liver - some BDZ might be administered by IV for what purpose
-
preanesthesia
anesthetic regimen
emergency treatment of seizures -
long term benzo?
T1/2? -
flurazepam, chlordiazepoxide, clorazepate, diazepam
>1day -
intermediate benzo?
T1/2? -
temazepam, estazolam
6-24 hrs -
short acting benzo?
T1/2? -
triazolam, zolpidem (not structurally a BDZ)
<6hrs - benzo MOA
-
positive allosteriv modulator of GABA Cl channel
binding site is distinct from GABA and barbiturate site
INCREASE SYNAPTIC INHIBITION
increase frequency of of channel opening in presence of GABA - do benzo have cardiorespiratotry effects?
- no
- what patients are adversely affected by high levels of benzo
- COPD, OSA
- CNS effects of BENZO
-
anxiolytic
sedation
muscle relax
anticonvulsant
hypnosis, retrograde amnesia
ataxia
stupor - do you become tolerant to benzos?
- to all effects except anxiolytic effects
- dependance depends on what two factors
-
dosage
T1/2 - to be effective benzos should:
-
have fast onset
not too short T1/2 life
not too long duration of action
produce refreshing sleep - used for preanesthetic medication to reduce anxiety, decrease recall and reduce anesthetic requirement
-
midazolam
lorazepam - clonazepam can also be used for? other than anxiety
- absence seizures
- BDZ can also be used to treat ?
-
status epilepticus
suppress dangerous symptoms during withdrawal from CNS depressants, like ethanol - completely antagonizes the effect of BDZ
- flumanezil
- an atypical anxiolytic is?
- buspirone
- buspirone is?
- an atypical anxiolytic
- what is more effective for anxiety? BDZ or buspirone
- BDZ
-
buspirone does not promote?
its anxiolytic effect may take how long to appear? -
sleep
1-2 weeks - buspirone also does not produce?
- rebound anxiety
- MOA of buspirone
-
partial agonist of 5-HT1a receptors
does not interact with GABA cl channels - well tolerated anxiolytic which lacks BDZ like side effects and is free of tolerance, dependence and withdrawel symptoms
- buspirone
- properties common to all non BDZ sedative hypnotics
-
progressive dose related CNS depression that terminates in sever respiratory depression and CV collapse
pharmacodynamic tolerance (cross tolerance included)
major physical dependance
possibility of lethal withdrawal - MOA of barbiturates
-
low doses potentiate GABAergic transmission
high doses promote Cl influc through GABA channels even in the absence of GABA - Barbiturate metabolism elimination
-
lipid soluble
short acting ones are lipid soluble (thiopental)10 minute duration of action
powerful induction of microsomal enzymes (phenobarbital) - barbiturate which may be used as anticonvulsant
- phenobarbital
- short acting barbiturate
- thiopental
- rate limiting step of alcohol metabolism
- alcohol dehydrogenase
- alcohol metabolism step inhibited by disulfiram
- aldehyde dehrdrogenase
- blood concentration of alcohol declines how with time?
- linearly (zero order kinetics)
- affect of alcohol on blood vessels
-
cutaneous casodilatation
overall vasoconstriction (especially coronary and cerebral beds exacerbating HTN) increasing BP - aversive therapy of treatment of alcoholism
-
disulfiram
inhibits aldehyde dehydrogenase leading to aversive effects due to increased levels of acetaldehyde - attenuates the rewarding effects of alcohol
- naltrexone