Benzos Flashcards
Pharmacological effects of Benzos (5)
- sedation
- anxiolysis
- anticonvulsant
- skeletal muscle relation
- antegrade amnesia
do benzos affect NMB dose?
No - Muscle relaxation is not sufficient for surgical relaxation
benzos facilitate inhibitory actions of what neurotransmitter?
GABA
benzos mimic inhibitory actions of what neurotransmitter
glycine
benzos mimic what two glycine actions?
muscle relaxation and antianxiety
benzos enhance what two GABA actions?
sedation and anticonvulsants
where are GABA and glycine located?
GABA – major inhibitory neurotransmitter in the CNS
Glycine is the major inhibitor neurotransmitter in the brainstem and spinal cord
MOA of benzos
bind to part of GABA receptor and causes an increase of binding of GABA to that receptor which
- opens Cl channels
- hyperpolarizes neuron
- causes inhibition of neuron to excitation
Do benzos affect GABA receptor directly?
Not really, they increase ability of GABA to bind to receptors which causes the effects of the benzos
2 important things to understand about the multiple sites on GABA receptor?
- Benzos don’t activate receptor, increase affinity of GABA
- dose of propofol, volatiles, etc will be reduced BC of the synergist effect of benzo and the fact that you already have something bound to that GABA receptor
The enhancement of the GABA inhibitory effect might explain what two effects?
sedation
anticonvulsant
Glycine-like inhibition in the spinal cord motor neurons accounts for muscle relaxation and anxiolysis r/t?
may be due to the inhibition of afferent conduction to anxiety centers at the brainstem level
GABA Has separate binding sites for benzodiazepine, barbiturates, and ETOH which means
If the receptor is “acted on” at more than one site, the inhibition of the CNS to excitation is synergistic
what type of agonist is benzo?
partial agonist whereas an inhaled agent is an agonist
what is the real agonist when thinking about benzos and effects?
GABA
Most commonly administered as premedication or IV sedation
Midazolam (Versed)
what is the interesting thing about versed and its ionization?
it is water soluble in the bottle, but becomes lipid soluble when in a solution with a pH>4 due to its imidazole ring
what two meds is midazolam compatible with?
opioids and LR
why is their no pain on injection (IV or IM) with midazolam?
does not need a carrying agent
Different routes of versed admin?
PO, IM, sublingual, intranasal, IV
Uses for midazolam -versed (4)
premedication, sedation, induction of anesthesia, maintenance of anesthesia
cards effects of Midazolam?
Decrease in BP r/t to SVR decrease
Increase in HR r/t SVR decrease
No change in CO
Hemodynamic effect exaggerated in hypovolemic patients
if you have a pt that is hypovolemic and you want amnesia and you have midazolam or scopalamine, what would you give?
scop because hemodynamic effects of midazolam are exaggerated with these patients
what is the cardioprotectant effect of midazolam?
makes adenosine last longer
Adenosine’s effect on cardio system?
it is an endogenous chemical
Reduces myocardial oxygen demand
Slows HR
Increase myocardial oxygen supply
Coronary vasodilation
what is verseds MOA on adenosine in body?
Decrease adenosine degradation by inhibiting the nucleoside transporter (mechanism for reuptake of adenosine into cells)
resp effects of midazolam? (3)
- Produces dose-dependent decreases in ventilation similar to diazepam (COPD worse)
- Apnea
- Depresses swallowing reflex and upper airway activity (OSA)
apnea can occur with midazolam with
Rapid injection of doses >0.15 mg/kg IV
With opioids
CNS effects midazolam?
- decreases CMRO2
- Cannot cause EEG to become isoelectric but CAN change amplitude and frequency
- tx seizures from local anesthetic toxicity
- excitement <1%
with midazolam cerebral blood flow is similar to what med class
barbiturates
what specifically does midazolam do to EEGs?
Alpha activity decreased
Beta activity increased
Unable to produce isoelectric EEG
what is the weird effect of midazolam on analgesia?
Analgesic effect of opioids reduced
Flumazenil enhanced analgesic effect of opioids
(only seen with one study)
what is the effect of versed on the Hypothalamic-Pituitary-Adrenal Axis
inhibits cortisol secretion
onset of midazolam?
Moves quickly to the brain, but “slow” onset (compared to thiopental) of
0.9 to 5.6 minutes
what route results in first-pass hepatic effect leaving only 50% to reach circulation.
oral (think peds)
Elimination ½ time versed
1-4 hours BUT has a short duration of action due to redistribution
(doubled in elderly)
metabolism of midazolam?
hydroxylation by hepatic microsomal oxidative mechanisms (C-P450)
Hepatic clearance rate is __ faster than lorazepam and __ faster than diazepam
5x
10x
Dosages of midazolam
Pediatric premedication: 0.3-0.5 mg/kg PO (30 min)
Sedation: 1 – 2.5 mg IV
Induction: 0.1 – 0.2 mg/kg IV
what are the positives of using versed on induction?
No nausea or vomiting
No emergence excitement
One hour later no difference in alertness, discharge time is similar in outpatients.
but there is a slower awake time than thiopental (1-2.5X)
Insoluble in water, dissolved in propylene glycol (pain on injection)
Diazepam (Valium)
Cardiovascular effects of diazepam - valium (4)
- Minimal decreases in BP, CO, and SVR
- -Less effects than barbiturates, midazolam
- Synergistic decreases with fentanyl
- Decreases exaggerated with hypovolemic patients
how long does it take PO dose of valium to reach peak concentration?
1 hour
Respiratory system effects of diazepam - valium
- depressed response CO2
- decrease in tidal volume
- apnea rarely occurs doses <10 mg
- will have minimal effects until you reach a dose of 0.2 mg/kg IV
CNS effects of valium
- decrease CMRO2, CBF, ICP
- skeletal muscle relaxant
- decreases MAC 30%
- anticonvulsant
- anxiolysis
- amnesia
list amnestic effect from best to worst with benzo
lorazepam, midazolam, diazepam
diazepam is highly lipid soluble which means:
quickly absorbed for GI tract, crosses the placenta
how is diazepam metabolized and into what two active metabolites??
hepatic microsomal enzymes into:
Desmethyldiazepam
Oxazepam
Only slightly less potent than diazepam
Drowsiness returns 6-8 hours after admin.
Causes prolonged effects of diazepam
Elimination ½ life: 48-96 hours
Desmethyldiazepam
*elderly
Elimination ½ life of diazepam is 21-37 hours, what three things can increase it even more
- age
- cirrhosis (5X)
- cimetidine (Tagamet) bc of its effect on liver enzymes
dose of valium for adults and peak effect time?
Dosage PO 10-15 mg (adult)
Peak effect 55 minutes
Insoluble in water, dissolved in polyethylene glycol or propylene glycol (less painful than diazepam)
Lorazepam (Ativan)
what two things limits the usefulness of lorazepam?
its slow onset and prolonged duration
Antegrade amnesia lasts up how many hours with ativan?
6 hrs
lorazepam is less Lipid soluble than what other benzo
diazepam
why does ativan produce a longer clinical effect?
slower release from the GABA receptors
dose of lorazepam and peak
Dose: 50 mcg/kg (up to 4 mg)
Peak concentration: 2-4 hours
Slow onset
elimination 1/2 life lorazepam
10-20 hours
why is diazepams elim 1/2 longer than lorazepam?
lorazepam has inactive metabolites
Novel, ultra-short acting “soft” designed benzo that was approved in 2020 that is also water soluble
Remimazolam (Byfavo)
Distribution ½ life of remimazolam - byfavo
0.2-2 mins [fast!]
metabolism of byfavo - remimazolam
Hydrolyzed by tissue esterases in the blood to inactive carboxylic acid
Context sensitive half time of remimazolam?
6 mins after 2 hours
7 mins after 8 hours
- doesnt hold on
where will you see remimazolam typically used?
GI endoscopy and bronchoscopies bc of the short duration
dose of remimazolam?
0.10, 0.15, 0.20 mg/kg
remimaz is better than prop and midazolam in what way?
respiratory failure was “almost zero.”
why is premedication not ideal with remimaz?
short duration and no oral preparation i.e only IV
Induction dose remimaz and maintenance
6-12 mg/kg/hr
Maintenance infusion: start at 1 mg/kg/hr, then titrate up or down
remimaz produced 2 longer side effects than prop but decreased another
LOC and time to ext was longer than prop, but hypotension less common
what pt population could remimaz be good for?
Sedation for critically ill patients
Theoretically, ideal due to organ independent metabolism and rapid clearance when discontinued for weaning of vent or neuro checks.
how much time needs to elapse before you give another dose of remimaz
2 minutes
