PreOp Meds: Midazolam

Question 1

What structural characteristic of midazolam stabilizes structure and allows for rapid metabolism?

Answer 1

• Imidazole Ring (lots of nitrogens)

Question 2

What two situations is midazolam primarily used for?

Answer 2

• Preop anxiolysis & conscious sedation

Question 3

How much more/less potent is midazolam than diazepam? Why is this?

Answer 3

• 2-3x more potent due to greater receptor affinity.

Question 4

What facilitates water solubility of midazolam?

Answer 4

• pH dependent ring opening
• pH < 3.5 = open ring = water soluble & protonated.
• pH > 4 = closed ring = lipid soluble & unprotonated.

Question 5

Why is midazolam non-irritating upon injection?

Answer 5

• No propylene glycol needed for stabilization

Question 6

Onset of midazolam occurs in ____ _______.
Peak effect occurs in ___ _______

Answer 6

• Onset: 1-2 minutes.
• Peak: 5 minutes

Question 7

Why is midazolam’s duration of action short?

Answer 7

Short due to rapid redistribution.

Question 8

What is the Elimination ½-time of midazolam?
How does this change in elderly patients?

Answer 8

• 2 hours
• Doubled in elderly patients (4 hours-ish)

Question 9

What is the Vd (volume of distribution) of midazolam?

Answer 9

• 1-1.5 L/kg (large due to lipid-solubility)

Question 10

What metabolizes midazolam?
What is the primary metabolite and it’s significance?

Answer 10

• CYP3A4
• 1-hydroxmidazolam (½ the activity of midazolam)

Question 11

What clears the active metabolite of midazolam?

Answer 11

• Kidneys

Question 12

What drugs will inhibit CYP450’s?

Answer 12

• Cimetidine
• Erythromycin
• CCBs
• Antifungals
• Fentanyl

Question 13

What is midazolam’s clearance in comparison to lorazepam and diazepam?

Answer 13

• 5x faster than lorazepam and 10x faster than diazepam.

Question 14

How does midazolam produce an isoelectric EEG?

Answer 14

• Trick question. No isoelectric EEG capabilities.

Question 15

Midazolam inhibits/preserves the vasomotor response to CO₂. What does this mean?

Answer 15

• Preserves: (↑CO₂ = vasodilation; ↓CO₂ = vasoconstriction)

Question 16

Why is midazolam a good choice for neuro cases?

Answer 16

• No change in ICP with administration

Question 17

What are the pulmonary effects of midazolam?

Answer 17

• Dose-dependent respiratory depression (increased with COPD).
• Swallow reflex depression (aspiration)
• Upper airway depression (aspiration)

Question 18

What are the cardiovascular effects of midazolam?

Answer 18

• Dose-dependent ↑HR & ↓BP

Question 19

How much does midazolam depress cardiac output?

Answer 19

• Trick Question. No CO depression; ↓SVR = ↓BP

Question 20

Significant hypotension can occur with midazolam administration in the presence of _____________.

Answer 20

hypovolemia

Question 21

What is the preop/intraop sedation dosing for midazolam in pediatric populations?
When do effects peak and what is the consequence of this?

Answer 21

• 0.25 - 0.5 mg/kg PO route
• Peaks in 20-30 min (give 30 min prior to OR)

Question 22

What is the preop/intraop dosing of midazolam in adult populations? When does the effect peak?

Answer 22

• 1-5mg IV
• Peaks in 5 minutes

Question 23

What is the induction dose for midazolam?
What drug is usually 2-3 minutes prior to this?

Answer 23

• 0.1-0.2 mg/kg IV over 30-60seconds
• Fentanyl 50-100mcg

Question 24

What is the postoperative sedation dose of midazolam?
How long should midazolam be used for long-term sedation? Why is this?

Answer 24

• 1-7 mg/hr IV.
• 2-3 days due to unclear effects on T-cell response.