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KM (Spring 2024) COPY of Anesthesia Pharm (Spring 2023) > Benzodiazepines (Exam I) > Flashcards

Benzodiazepines (Exam I) Flashcards

1
Q

Differentiate sedatives and hypnotics.

A
  • Sedatives: induce calm/sleep
  • Hypnotics: induce hypnosis/sleep
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2
Q

When is anesthesia awareness most common?
What are the rates of this occurring?

A
  • During sedation cases and during emergence.
  • 1:1000 (or 1:10,000 per some studies)
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3
Q

What is the mechanism for less EEG activity seen during anesthesia/sedation?

A
  • Less cerebral blood flow (CBF) and cerebral metabolic requirement of oxygen (CMRO₂) = less metabolism = less EEG activity.
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4
Q

What was the first compressed EEG?
Give the details of the study exploring its use.

A
  • Bispectral analysis
  • 1500 subjects w/ 5000 hours of EEG signaling
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5
Q

What drugs were utilized in the bispectral analysis study?

A
  • Isoflurane/ O₂
  • Propofol/nitrous
  • Propofol/alfentanil
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6
Q

Which drugs exhibit a strong correlation between BIS change and patient movement?
Which drugs do not exhibit this correlation?

A
  • Hypnotic drugs
  • Narcotics
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7
Q

In the BIS study, what reading indicated that a patient was for sure unconscious?

A
  • <58
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8
Q

In the BIS study, a reading of <65 indicated a ___% of return to consciousness within the minute.

A
  • 5%
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9
Q

What is a normal BIS range?

A
  • 40-60
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10
Q

What are the four parameters (other than the BIS itself) noted on a BIS monitor?

A
  • SQI
  • EMG
  • EEG
  • SR
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11
Q

What is the SR noted on a BIS monitor?
What would an SR of 60 indicate?

A
  • Suppression Ratio (how many seconds per minute that the EEG is flat)
  • SR of 60 means EEG is completely flat (could be brain death).
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12
Q

Name drugs that could suppress EEG activity.

A
  • Hypnotics, volatiles, NMBDs, Opioids
  • β-blockers
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13
Q

Name drugs that could enhance EEG activity.

A
  • Ketamine, epinephrine
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14
Q

What are the five main functions of a benzodiazepine?

A
  • Anxiolysis
  • Sedation
  • Anterograde amnesia
  • Anticonvulsant
  • Spinal-cord mediated muscle relaxation
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15
Q

What is the only “thing” that can cause retrograde amnesia?

A
  • ECT (electroconvulsive therapy)
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16
Q

Why are written instructions given to a patient after waking up from benzodiazepine sedation?

A
  • Anterograde amnesia effects last longer than sedative effects.
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17
Q

Can benzodiazepines be substituted for NMBs due to their spinal-cord mediated skeletal muscle relaxation?

A
  • No; not adequate for true paralysis
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18
Q

__________ drugs can induce CYP450’s.

A

Barbiturates

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19
Q

What is the mechanism of action of benzodiazepines?

A
  • Enhancement of GABA binding by changing receptor affinity. Allows for greater Cl⁻ influx and thus hyperpolarization.
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20
Q

Which GABA site do benzodiazepines bind to?

A
  • Trick question. Benzo’s do not bind directly to GABA sites.
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21
Q

How many subunits are present in a GABA receptor?
Where do GABA molecules bind on said receptor?

A
  • Five
  • In-between the α1 & β2 subunits.
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22
Q

What subunits do Benzodiazepines bind to on the GABA receptor?

A
  • In-between α1 & γ2
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23
Q

GABA receptors with α1 subunits exhibit what properties when bound?
How abundant are these specific receptors and where are they found?

A
  • Sedation, amnesia, & anticonvulsion
  • Most abundant: cerebral cortex, cerebellar cortex, & thalamus.
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24
Q

GABA receptors with α2 subunits exhibit what properties when bound?
How abundant are these specific receptors and where are they found?

A
  • Anxiolysis & skeletal muscle relaxation
  • Less abundant: hippocampus & amygdala
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25
Q

What other drugs bind to GABA receptors besides benzodiazepines?
What is the result if one of these drugs is given in conjunction with benzodiazepines?

A
  • Barbiturates, Etomidate, Propofol, & EtOH
  • Risk of overdose & cross-tolerance
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26
Q

Benzodiazepines are highly _____ soluble and highly _______ bound.

A
  • Lipid; protein
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27
Q

What factors cause differing effects amongst benzodiazepines?

A
  • Potency
  • Lipid solubility
  • Redistribution (to peripheral tissues)
  • Pharmacokinetics
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28
Q

List EEG waves from greatest activity to least activity.

A
  • Gamma → Βeta → Αlpha → Theta → Delta
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29
Q

What general effect(s) do benzodiazepines have on EEG activity?

A
  • Decreased αlpha activity
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30
Q

What platelet effects do benzodiazepines have?

A
  • Inhibitory towards platelet aggregation (very slight, only in vitro studies)
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31
Q

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

A
  • Imidazole Ring (lots of nitrogens)
32
Q

What two situations is midazolam primarily used for?

A
  • Preop anxiolysis & conscious sedation
33
Q

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

A
  • 2-3x more potent due to greater receptor affinity.
34
Q

What facilitates water solubility of midazolam?

A
  • pH dependent ring opening
  • pH < 3.5 = open ring = water soluble & protonated.
  • pH > 4 = closed ring = lipid soluble & unprotonated.
35
Q

Why is midazolam non-irritating upon injection?

A
  • No propylene glycol needed for stabilization
36
Q

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

A
  • Onset: 1-2 minutes.
  • Peak: 5 minutes
37
Q

Why is midazolam’s duration of action short?

A

Short due to rapid redistribution.

38
Q

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

A
  • 2 hours
  • Doubled in elderly patients (4 hours-ish)
39
Q

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

A
  • 1-1.5 L/kg (large due to lipid-solubility)
40
Q

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

A
  • CYP3A4
  • 1-hydroxmidazolam (½ the activity of midazolam)
41
Q

What clears the active metabolite of midazolam?

A
  • Kidneys
42
Q

What drugs will inhibit CYP450’s?

A
  • Cimetidine
  • Erythromycin
  • CCBs
  • Antifungals
  • Fentanyl
43
Q

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

A
  • 5x faster than lorazepam and 10x faster than diazepam.
44
Q

How does midazolam produce an isoelectric EEG?

A
  • Trick question. No isoelectric EEG capabilities.
45
Q

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

A
  • Preserves: (↑CO₂ = vasodilation; ↓CO₂ = vasoconstriction)
46
Q

Why is midazolam a good choice for neuro cases?

A
  • No change in ICP with administration
47
Q

What are the pulmonary effects of midazolam?

A
  • Dose-dependent respiratory depression (increased with COPD).
  • Swallow reflex depression (aspiration)
  • Upper airway depression (aspiration)
48
Q

What are the cardiovascular effects of midazolam?

A
  • Dose-dependent ↑HR & ↓BP
49
Q

How much does midazolam depress cardiac output?

A
  • Trick Question. No CO depression; ↓SVR = ↓BP
50
Q

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

A

hypovolemia

51
Q

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

A
  • 0.25 - 0.5 mg/kg PO route
  • Peaks in 20-30 min (give 30 min prior to OR)
52
Q

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

A
  • 1-5mg IV
  • Peaks in 5 minutes
53
Q

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

A
  • 0.1-0.2 mg/kg IV over 30-60seconds
  • Fentanyl 50-100mcg
54
Q

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

A
  • 1-7 mg/hr IV.
  • 2-3 days due to unclear effects on T-cell response.
55
Q

Why does diazepam burn on injection?
Is there a better formulation?

A
  • insoluble in water so it’s dissolved in propylene glycol.
  • Soybean formulation available but more expensive.
56
Q

What is the onset of diazepam?
What is the E ½ time of diazepam?
What is the Vd of diazepam?

A
  • Onset: 1-5 minutes
  • E ½ = 20-40 hours (very protein-bound)
  • Vd = 1-1.5 L/kg
57
Q

What metabolizes diazepam?
What are its primary metabolites and what is it’s significance?

A
  • CYP3A4
  • Desmethyldiazepam & oxazepam
  • Metabolites are nearly as potent as diazepam and hit 6-8 hours after administration.
58
Q

What is the seizure dosing for diazepam?
What seizures is it utilized for?

A
  • 0.1 mg/kg IV
  • DT’s, status epilepticus, lidocaine toxicity seizures.
59
Q

What are the EEG effects of diazepam?

A
  • Can produce isoelectric EEG.
60
Q

What are the pulmonary effects of diazepam?

A
  • Minimal; any depressant effects are reversed by surgical stimulation.
61
Q

What are diazepam’s effects on the cardiovascular system?
What effects would be seen with adjunct opioids?

A
  • Minimal decreases in BP, CO, and SVR (used be agent for cardiac cases)
  • Additive BP changes when used with opioid.
62
Q

What are diazepam’s effects on the musculoskeletal system?

A
  • Decreases skeletal muscle tone
63
Q

What is the induction dose of diazepam?
When would one decrease the dose by 50%?

A
  • 0.5-1 mg/kg IV
  • 50% cut with elderly, liver patients, and with concurrent opioid use.
64
Q

Of midazolam, diazepam, and lorazepam, which is the most potent sedative/amnestic?

A
  • Lorazepam
65
Q

Which benzodiazepine has the slowest onset of action?

A
  • Lorazepam
66
Q

When is peak effect seen with lorazepam?

A
  • 20-30 min with IV dose (1-4mg)
67
Q

What is the E ½ time of lorazepam?

A
  • 14 hours
68
Q

Which benzodiazepine’s metabolism is less dependent on CYP450’s?

A
  • Lorazepam (better drug for liver patients)
69
Q

When is lorazepam most useful?

A
  • Post-operative sedation
70
Q

What is flumazenil (Romazicon)?

A
  • Competitive antagonist for benzodiazepine receptor. (preventative and reversal)
71
Q

What metabolizes flumazenil? What are its metabolites?

A
  • CYP450’s
  • No active metabolites
72
Q

What is the dosing of flumazenil?

A
  • 0.2mg IV titrated to consciousness (repeat 0.1mg q1min til 1mg total)
73
Q

What is the sedation reversal dose range of flumazenil?

A
  • 0.3 - 0.6 mg
74
Q

What is the complete reversal dose range of flumazenil?

A
  • 0.5 - 1 mg
75
Q

If the patient is still unconscious after 0.5 - 1mg of flumazenil has been given, what should be considered?

A
  • Other intoxicants (opioids, EtOH, etc)
76
Q

What is the duration of flumazenil?

A
  • 30 - 60 min
77
Q

When is flumazenil contraindicated?

A
  • When needed antiepileptics are being given
  • If it precipitates acute EtOH withdrawal.

KM (Spring 2024) COPY of Anesthesia Pharm (Spring 2023) (103 decks)

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