Benzo's - Midazolam Flashcards
What facilitates water solubility of midazolam?
pH dependent ring opening
pH < 3.5 = open ring = water soluble & protonated.
pH > 4 = closed ring = lipid soluble & unprotonated.
Why is midazolam non-irritating upon injection?
No propylene glycol needed for stabilization
Onset of midazolam occurs in ____ _______.
Peak effect occurs in ___ _______.
Onset: 1-2 minutes.
Peak: 5 minutes
Why is midazolam’s duration of action short?
Short due to rapid redistribution.
What is the Elimination ½-time of midazolam?
How does this change in elderly patients?
2 hours
Doubled in elderly patients (4 hours-ish)
What is the Vd (volume of distribution) of midazolam?
1-1.5 L/kg (large due to lipid-solubility)
What metabolizes midazolam?
What is the primary metabolite and it’s significance?
CYP3A4
1-hydroxmidazolam (½ the activity of midazolam)
What clears the active metabolite of midazolam?
Kidneys
What drugs will inhibit CYP450’s?
Cimetidine
Erythromycin
CCBs
Antifungals
Fentanyl
What is midazolam’s clearance in comparison to lorazepam and diazepam?
5x faster than lorazepam and 10x faster than diazepam.
How does midazolam produce an isoelectric EEG?
Trick question. No isoelectric EEG capabilities.
Midazolam inhibits/preserves the vasomotor response to CO₂. What does this mean?
Preserves: (↑CO₂ = vasodilation; ↓CO₂ = vasoconstriction)
Why is midazolam a good choice for neuro cases?
No change in ICP with administration
What are the pulmonary effects of midazolam?
Dose-dependent respiratory depression (increased with COPD).
Swallow reflex depression (aspiration)
Upper airway depression (aspiration)
What are the cardiovascular effects of midazolam?
Dose-dependent ↑HR & ↓BP
How much does midazolam depress cardiac output?
Trick Question. No CO depression; ↓SVR = ↓BP
Significant hypotension can occur with midazolam administration in the presence of _____________.
hypovolemia
What is the preop/intraop sedation dosing for midazolam in pediatric populations?
When do effects peak and what is the consequence of this?
0.25 - 0.5 mg/kg PO route
Peaks in 20-30 min (give 30 min prior to OR)
What is the preop/intraop dosing of midazolam in adult populations? When does the effect peak?
1-5mg IV
Peaks in 5 minutes
What is the induction dose for midazolam?
What drug is usually 2-3 minutes prior to this?
0.1-0.2 mg/kg IV over 30-60seconds
Fentanyl 50-100mcg
What is the postoperative sedation dose of midazolam?
How long should midazolam be used for long-term sedation? Why is this?
1-7 mg/hr IV.
2-3 days due to unclear effects on T-cell response.
How much more/less potent is midazolam than diazepam? Why is this?
2-3x more potent due to greater receptor affinity
What two situations is midazolam primarily used for?
Preop anxiolysis & conscious sedation
What structural characteristic of midazolam stabilizes structure and allows for rapid metabolism?
Imidazole Ring (lots of nitrogens)
