Benzodiazepines Flashcards
benzos: 5 main pharmacological effects
anxiolysis sedation anterograde amnesia anticonvulsant actions muscle relaxation (spinal level)
what do we use benzos for the most
anxiolysis
benzos and muscle relaxation
no muscle relaxation
do not affect muscle relaxant doses
benzos and hepatic metabolism
do not induce hepatic metabolism
less potential for tolerance/abuse than barbs, opioids
benzos and cerebrovascular response
preserves cerebrovascular response
greater margin of safety
benzos replaced what for premed/MAC cases
barbs
benzos structure
benzene ring with 7 member diazepine ring
benzos mechanism of action
facilitate action of GABAa
increase affinity of GABAa to receptor
do benzos mimic GABAa?
NO, does not directly activate GABAa receptor
what does increase of affinity of GABA mean?
open Cl channel
increase in Cl in cell
hyperpolarizes cel in post synapse
benzos are different in 3 ways
potency, lipid solubility, pharmacokinetics
in general, benzos are
highly lipid soluble, highly bound to albumin
if pt is drunk, do you give benzos?
no, the ETOH is already binding to the GABAa receptors
versed preparation, shape, potency, effect site equilibration time, hepatic effect, % protein bound, redistribution/duration time, elimination T1/2
water soluble imidazole ring 2-3x more potent than diazepam 0.9-5.6 min effect site equilibration, increases with age extensive first pass effect 90-98% protein bound rapid redistribution, short duration T1/2 = 1-6.5 hrs
versed metabolism
extensive first pass effect hydroxylation to water soluble compound 1,4 hydroxymidazolam 1 hydroxymidazolam is an active metabolite conjugated, excreted in urine renal failure does not affect midazolam
versed CNS efects
decrease CMRO2, drops CBF
does not produce isoelectric EEG
preserves cerebrovascular response to CO2
does not stop ICP response to laryngoscopy
anticonvulsant, amnesic
Rare paradoxical excitation
versed respiratory effects
dose dependent decrease in ventilation
speed of injection makes a big difference
with opioids, hypoxemia, hypoventilation is enhanced
depress swallowing, upper airway activity
versed cv effects
at induction, decreases SVR, BP
CO unchanged
doesn’t stop HR, BP changes with intubation
versed doses
premed/peds: 0.25 - 0.5 mg/kg PO, max PO 20mg
IV sedation adults: 1-2.5 mg IV up to 5 mg
induction 0.1 - 0.2 mg/kg over 30-60 sec
maintenance - incremental, infusion
valium solubility, viscosity, pH, injection technique, protein binding, PO absorption
lipid soluble in organic solvents so hurts on injection very viscous, pH 6.6-6.9 highly protein bound rapidly absorbed in GI
valium metabolism
oxidation: n-demethylation to:
desmethyldiazepam
oxazepam
temazepam in liver
valium and metabolites
desmethyldiazepam further oxidized, so liver function will affect this
cimetadine and liver function
inhibits CP450 system
valium elimination T1/2
21-37 hrs, longer with age
demethyldiazepam 48-96 hrs
valium pharmacodynamics
minimal changes in SVR, BP, CO (<20%)
otherwise similar to midazolam
valium dosage
premed/oral: 10-15 mg
premed/IV 0.2 mg/kg (reduces MAC)
induction 0.5-1 mg/kg IV
lorazepam potency, metabolites, T1/2, metabolism, solvent
5-10x more potent than diazepam inactive metabolite T1/2 10-20 hr less influenced by changes in liver, age propyl glycol solvent, so hurts
lorazepam dosage
premed/PO 50 mcg/kg max 4 mg
lorazepam anesthesia usefulness
slow onset, limited usefulness for us
~2hrs to peak plasms [ ]
flumazenil (romazicon) derivative
imidazobenzodiazipine
high affinity for benzo specific receptors
flumazenil duration
30-60 min, may need to repeat doses
flumazenil dosage
- 2 mg IV initial, wait 2 minutes
0. 1 mg IV 60 sec intervals up to 3 mg
flumazenil use
can be used for differential diagnosis IV infusion 0.1-0.4 mg/hr antagonizes depression of ventilation, sedation no acute anxiety hepatic metabolism renal excretion
