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

Benzos Flashcards by Adriana Comerford

Pharmacological effects of Benzos (5)

sedation
anxiolysis
anticonvulsant
skeletal muscle relation
antegrade amnesia

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do benzos affect NMB dose?

No - Muscle relaxation is not sufficient for surgical relaxation

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benzos facilitate inhibitory actions of what neurotransmitter?

GABA

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benzos mimic inhibitory actions of what neurotransmitter

glycine

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benzos mimic what two glycine actions?

muscle relaxation and antianxiety

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benzos enhance what two GABA actions?

sedation and anticonvulsants

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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

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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

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Do benzos affect GABA receptor directly?

Not really, they increase ability of GABA to bind to receptors which causes the effects of the benzos

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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

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The enhancement of the GABA inhibitory effect might explain what two effects?

sedation

anticonvulsant

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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

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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

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what type of agonist is benzo?

partial agonist whereas an inhaled agent is an agonist

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what is the real agonist when thinking about benzos and effects?

GABA

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Most commonly administered as premedication or IV sedation

Midazolam (Versed)

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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

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what two meds is midazolam compatible with?

opioids and LR

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why is their no pain on injection (IV or IM) with midazolam?

does not need a carrying agent

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Different routes of versed admin?

PO, IM, sublingual, intranasal, IV

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Uses for midazolam -versed (4)

premedication, sedation, induction of anesthesia, maintenance of anesthesia

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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

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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

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what is the cardioprotectant effect of midazolam?

makes adenosine last longer

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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)

1. Produces dose-dependent decreases in ventilation similar to diazepam (COPD worse) 2. Apnea 3. 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?

1. decreases CMRO2 2. Cannot cause EEG to become isoelectric but CAN change amplitude and frequency 3. tx seizures from local anesthetic toxicity 4. 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

1. decrease CMRO2, CBF, ICP 2. skeletal muscle relaxant 3. decreases MAC 30% 4. anticonvulsant 5. anxiolysis 6. 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

1. age 2. cirrhosis (5X) 3. 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