Benzos

Question 1

Flumazenil DOA? Metabolism?

Answer 1

30-60 min, meaning you may need to redose

Hepatic metabolism, renal excretion

Question 2

Why is there a ceiling effect with benzos?

Answer 2

Because all it can do is assist GABA to open the Cl- channels. After that, it can’t do anything else to achieve any effects.

Question 3

Midazolam CV effects?

Answer 3

Cardio stable;

CO unchanged

Dec SVR at induction dosage

Dec BP from anxiolysis

Doesn’t attenuate laryngoscopy HR/BP changes

Question 4

Benzodiazepine MOA

Answer 4

• Facilitate action of GABA and GABA-A receptor, enhance affinity of GABA to the receptor (but DOES NOT activate GABA-A receptor)
• This leads to Cl channels open, inc conductance, hyperpolarization of post-synaptic membrane, increased resistance of post-synaptic membrane to excitation

Question 5

Diazepam E1/2t?

Answer 5

Diazepam is ≈ day (20-50h)

Desmethyldiazepam is 2-4 days!

Question 6

Lorazepam solvent?

Answer 6

Propylene glycol

Question 7

Flumazenil (romazicon) dose?

reversal

(what about infusion?)

Answer 7

0. 2 mg IV, wait 2 min,
1. 1 mg IV subsequent doses at 60 sec intervals to

max total 3 mg

Infusion: 0.1-0.4 mg/h

Question 8

Which benzodiazepine is most potent?

Answer 8

Lorazepam (ativan) It is 5-10x more potent than diazepam

Question 9

Structure of midazolam (versed)?

Answer 9

Water soluble preparation

Imidazole ring

(same compound that etomidate has)

Question 10

Midazolam metabolism?

Answer 10

Extensive hepatic metabolism

ACTIVE METABOLITE: 1-hydroxy-midazolam

Conjugated and excreted in the urine

Renal failure doesn’t effect VD, E1/2t, or clearance

Question 11

Diazepam metabolism?

Answer 11

Oxidation, n-demethylation to desmethyldiazepam (ACTIVE METABOLITE)

which is oxidized, conjugated, and excreted in the urine

Question 12

Dosage of midazolam for…

Premedication peds, IV sedation adults, Induction

Answer 12

Premed peds: 0.25-0.5 mg/kg po (not on drug cards)

Peds po dose max 20mg IV

sedation adults (premedication): 0.5-5 mg IV or 0.04-0.08 mg/kg

Induction: 0.05-0.35 mg/kg over 30-60 sec

*Per drug cards, not powerpoint

Question 13

Benzos are highly _____ (water/lipid) soluble and _____ (high/low) protein binding

Answer 13

Lipid soluble

High PB

Question 14

Flumazenil antagonizes what effects of benzos?

Answer 14

Antagonizes depression of ventilation and sedation

Question 15

What does it mean if a drug has a short effect site equilibration time?

Answer 15

It means that the effects on the brain occur promptly after IV administration

Question 16

Where are GABAa receptors found?

Answer 16

On POST-synaptic neurons in the CNS

There are barely any GABA receptors outside the CNS

Question 17

What is the reversal for benzodiazepines?

Answer 17

Flumazenil (Romazicon)

Specific, competitive benzo antagonist with high affinity for benzo receptors

imidazobenzamine derivative

Question 18

Do benzos potentiate the neuromuscular blockade?

Answer 18

Nope

Question 19

Midazolam CNS effects?

Answer 19

Decreases CBF and CMRO2

Does NOT attenuate ICP response to laryngoscopy

Anticonvulsant and amnestic

Question 20

What is flumazenil (romazicon) a derivative of?

Answer 20

Imidazobenzodiazepine

Question 21

Benzodiazepine structure?

Answer 21

Benzene ring fused with 7-member diazepine ring

Question 22

Lorazepam metabolism and e1/2t?

Answer 22

Metabolites are INACTIVE

Metabolism effected by hepatic function and age E1/2t 10-20h

Slow onset, IV takes 20-30 min to peak, not used as often in OR

Question 23

Do benzos induce hepatic enzymes?

Answer 23

Nope

Question 24

Midazolam respiratory effects?

Answer 24

Decrease in ventilation (dose dependent)

Hypoxemia and hypoventilation enhanced in presence of opioid

Depress swallow reflex

decreased upper airway activity

Question 25

Benzodiazepines 5 pharmacological effects?

Answer 25

Anxiolysis

Asleep (sedation)

Anterograde

Amnesia

Anticonvulsant

Muscle Relaxation- spinal

Question 26

Diazepam dosages for… premedication oral and IV; induction; anticonvulsant?

Answer 26

Premedication oral: 10-15mg

Premedication IV: 0.2 mg/kg (reduces MAC)

Induction: 0.5-1 mg/kg IV

Anticonvulsant: 0.1 mg/kg IV

Question 27

How does potency of midazolam compare to diazepam?

Answer 27

Midazolam is 2-3x more potent than diazepam

Question 28

What is the order of benzos from least to most potent?

Answer 28

DiVA

Diazepam, versed, ativan

Question 29

Lorazepam dosage?

premedication/po

IV

Answer 29

50 MCG/kg (max 4 mg) PO

1-4 mg IV

Question 30

Diazepam is prepared in what solvents?

Answer 30

Propylene glycol

Benzyl alcohol

Painful IV/IM injection

Question 31

GABA binds to ________

Answer 31

the 2 beta sites

Question 32

benzos bind to the _______

Answer 32

1. gamma site
2. GABA-A