Sedatives I and II Flashcards
1. List the principal criteria for the appropriate use of sedative-hypnotic/anxiolytic agents. 2. List the prototype barbiturates, benzodiazepines, and GABAA-alpha1 selective agonists, describe their clinical uses, their mechanism and site of action, and how their pharmacokinetic differences provide the basis for selection of which agent to use and for what purpose. 3. List the major side effects and abuse potential of the prototype barbiturates, benzodiazepines, and GABAA-alpha1 selective ago
Standard reasons to treat anxiety w/drugs
1) anxiety
2) not for 8 hours of sleep
3) when it affects quality of life
MOA of Barbiturates
not really known, but seem to be GABAA agonist
Long acting barbo class
phenobarbital
phenobarbital t 1/2
80-120 hrs
pentobarb t 1/2
15-48 hrs
intermediate acting barbo
pentobarbital
short acting barbo
thiopental
clincal use for barbos
induction in general anesthesia and seziure disorders
old use for barbos
insomnia/anxiety
CNS activity of barbos
sedation to coma/death
state resembaling natural sleep
anticonvulsant
sx of barbo OD
comatose
bradypnea
marked hypotension
weak rapid pulse
TX for barbo OD
ABC rule out narcotics gastric lavage bicarb hemodialysis
ways tolerence to barbos comes about
induction of P450
cross-tolerence to all CNS depressents
drug class with potentially life-threatening dependance
barbos
early stages of barbo withdrawal sx
weakness, trembling, insomnia, and abdominal cramps
reversal of early stage barbo withdrawal
CNS depressant
when can barbo withdrawal be reversed
early only
sx of late stage barbo withdrawal
orthostatic hypotension, delirium, convilsions leading to status elipepticus
lenght of barbo withdrawl
7-9 days
contraindications of barbos
pts with hx or fam hx of acute intermittent porphyria
DOC class for anxiety
benzos
DOC for rapid treatment of panic attacks
benzos
prototype benzo
diazempam
CNS activity of benzos
sedative/hypnotic anxiolytic anticonvulsant muscle relaxant amnestic
anti anxiety that does not induce P450
benzo
advantages of benzos
safety, no induction of P450, mild withdrawal
MOA of benzo
binds GABAA receptor, increases CL- channel increasing frenquency of openings and release of GABA throughout CNS
GABA receptor that benzos bind to
alpha 1,2,3,and 5
GABA receptor mediating sedative properties of benzo
a 1, possibly 3
GABA receptor mediating anxiolytic properties of benzo
a2, possibly 3
GABA receptor mediating anticonvulsant properties of benzo
a3, possibly 1
GABA receptor mediating muscle relaxant properties of benzo
a2
benzo antagonist
flumazenil
clinical uses of benzos
treatment of anxiety
sleep disorders
benzos most effective in pts showing
high levels of emotional and somatic sx low levels of depression convulsive disorders neuromusclular disorders preop meds treatment of withdrawal from CNS depressents
time course of improvement from benzos
1-2 weeks
sedative that has no peripheral effects
benzo
only benzo used IM
lorazepam
benzos with no active metabolite
lorazepam, temazepam, triazolam
elimanation time for benzos
very long
sx of benzo withdrawal (low dose)
anxiety, rachycardia, palps, anorexia, blurred vision, muscle cramps
how to safely withdraw from benzos
tapering dose, w/wo switching to long active benzo or phenobarital
propanolol (not for more than 2 weeks)
sx of high dose benzo withdrawal
anxiety, seizures, psychosis, hyperpyrexia, death
prototype benzo
diazepam, alprazolam, lorazepam, chloridiazepoxide,
longest actiing benzo
diazepam, flurazepam
benzo with no active metabolites
lorazepam
danger of flumazenil
may precipate benzo withdrawal
contraindications for flumazenil
hx of seizures
barbo or TCA OD
advantages of Benzos for sleep
safety produce marked sedation does not disrupt REM sleep does not induce p450 milder withdrawal syndrome
prototype benzos used for sleep
flurazepam, larazepam, , temazepam, triazolam
long acting benzo that are used for sleep that only the metabolites are active
flurazepam
IM benzo with no active metabolites
lorazepam
benzo used for sleep with high abuse potential, no active metabolites short half life
triazolam
halcion generic
triazolam
sleep aid drug that can cause bizzare behavior, agitation, hallucination
triazolam (halcion)
buspirone MOA
NOT an GABA drug, may act on serotonin
clinical use of buspirone
anti-anxiety
anti-anxiety drug with NO sedative, anticonvulsant or muscle relaxant effects
buspirone
anti-anxiety drug with good use in elderly pts
buspirone
anti-anxiety with good first pass effect
buspirone
anti-anxiety with no cross-tolerance
buspirone
anti-anxiety drug that displaces digoxin
buspirone
GABAA a1 agonists
zolpidem, zaleplon, eszopiclone
GABAA a1uses
decrease sleep latency, decrease total REM sleep and increase Stage 2
GABAA a1 effects
less anti (anxiety/convulsant/relaxant) effects than benzos
ambien
zolpidem
class of sleep drugs that are metabolized by liver
GABAa a1 agonists
metabolized by oxidation of methyl group
zolipidem
metabolized by CYP3A4
zaleplon
metabolized by CYP3A4 and CYP2E1
eszopiclone
sleep aids not to be used in sleep apnea
GABAA a1
glass of sleep aids that can cause residual daytime sedation
zolpidem, eszopiclone
sleep aid that can cuais dizzyness and GI problems
zolpidem
sleep aid that can cause birth defects and potential pre/post natal survival
zaleplon
sleep aid with SE including bad tase, headaches, dizziness and dry mouth
eszopiclone
GABAA a1 drug with rebound insomnia
eszopicline
GABAA a1 + SSRI =
halluciations
inhibitors of CYP3A4 and CYP2E1 can increase serum concentrations of…
eszopiclone
drug class used for situational anxiety
beta blockers
antihistamine used for sedative
hydroxyzine
rationale for hydroxyzine use
pts with hx of abusing standard sedatives
never ever ever give most sedatives to these pts
folks with sleep apnea
why don’t you give sedatives to pts with sleep apnea
may increase hypoxia and hypercarbia
