Benzodiazepines Exam 1 Flashcards
Sedative/hypnotics definition
Drug that induces sleep, calm or hypnosis
How is EEG monitoring used to measure drug effects?
Anesthesia alters CBF and CMRO2.
CBF and CMRO2 relate to EEG activity.
What is BIS monitoring?
Processed EEG compacted into one waveform.
Helps determine level of sedation/consciousness.
BIS 100 = awake
BIS 0 = coma
What number on the BIS indicates loss of consciousness?
BIS < 58
BIS < 65 indicates…
<5% chance of consciousness within 50 seconds
SQI on BIS monitor
Signal quality index. Measures quality or lack of interference.
SR on BIS monitor
Suppression Ratio.
Percentage of time that the EEG signal is suppressed or flat
***anesthesia should not see a SR of zero (indicates oversedation or brain death)
Examples of BIS suppressants (5)
- Hypnotics
- volatiles
- NMBs
- opioids
- beta blockers
Examples of BIS stimulants (2)
Ketamine, Epinephrine
Ideal range for BIS under general anesthesia
40-60
Pharmacologic effects of BZDs (5)
- Anxiolytic
- Sedation
- Anterograde amnesia (forward)
- Anticonvulsant
- Skeletal muscle relaxation (not paralysis)
BZD benefit over barbiturates (3)
- Less tolerance or abuse potential
- Fewer/less severe side effects
- Don’t induce CYP450
BZD MOA
Enhances effects of GABA on GABA-A receptors
enhanced open of chloride channels
hyperpolarization of neuron, less firing
GABA alpha-1 effects (3)
- Sedative
- Amnesia
- Anticonvulsant
GABA alpha-2 effects (2)
- Anxiolytic
- Skeletal muscle relaxation
Synergistic drugs also acting on GABA-A (4)
Barbiturates, Etomidate, Propofol, Alcohol
BZD EEG effects (2)
- Decrease alpha wave activity, relaxation
- Some able to flatten brain waves
Midazolam trade name
Versed
Versed amnesia vs sedation effects
Amnestic effects last longer than sedation effects
Versed solubility with pH
< 3.5 pH = water soluble, protonated (ring open) (inactive form)
>4 pH = lipid soluble, unprotonated (ring closed) (active form)
Versed onset and peak effect
Onset: 1-2 min
Peak: 5 min
Versed protein binding
Extensively bound 96-98%
BZD reversal drug
Flumazenil (Romazicon)
Versed E 1/2 time
2 hours. Doubled in elderly pts.
Versed Vd
Large (1000ml-1500ml/kg)
Versed metabolism
CYP3A4 (hepatic Microsomal enzymes)
Significant Drugs that can decrease BZD metabolism by CYP inhibition (FACCE)
- Fentanyl
- Antifungals
- Cimetidine, CCBs
- Erythromycin
Versed cerebral flow effects
Decrease CMRO2. Decrease CBF. (Both dose related)
Versed CNS effects (2)
- Potential anticonvulsant
- Unable to produce isoelectric EEG (flatline)
Versed CO2 cerebral flow effects
High CO2 = cerebral vasodilation
Low CO2 = cerebral vasoconstriction
Versed preserves CO2 vasomotor response
Versed ICP effects
No effect on ICP (neuro-safe)
Versed pulmonary effects
Dose dependent decrease in ventilation
Versed airway effects
Depresses swallow reflex and upper airway activity
increased risk of aspiration
Versed CV effects
Dose dependent increase HR and decreased BP
(CO unchanged d/t compensation)
Versed sedation/anxiolysis dosing (adult)
1-5 mg IV. Peaks 5 min
Versed sedation/anxiolysis children dose
0.25-0.5 mg/kg oral. Peak 20-30 min
Versed induction dose
Not common as induction.
0.1-0.2 mg/kg IV over 30-60 sec
followed by fentanyl 50-100 mcg
Versed Postoperative sedation dose
1-7 mg/hr IV
Not recommended for use more than 2-3 days d/t immune/T cell effects
Diazepam trade name
Valium
Valium protein binding
Highly protein bound
Valium duration (comp)
More prolonged duration than versed. Rarely used in anesthesia.
Valium solubility
Insoluble in water
Need propylene glycol = pain on injection
Valium onset and duration (comp)
Onset: 1-5 minutes. Duration longer than versed.
Valium E 1/2 time
20-40 hours.
Valium metabolism
CYP3A
Active metabolite nearly as potent (48-96 hr)
return of drowsiness 6-8 hrs
Valium cerebral flow effects
Dose related decrease in CMRO2 and CBF.
Valium anticonvulsant dose
0.1 mg/kg IV.
Valium EEG effects
Can produce isoelectric EEG (flatline).
Valium pulmonary effects
Minimal effects on ventilation.
Valium CV effects
Minimal decrease in BP, CO, and SVR.
Valium induction dose
0.5-1 mg/kg IV
Decrease 25-50% in: elderly, liver disease, presence of opioids
Valium neuromuscular effects
Skeletal muscle relaxant (not paraytic)
tolerence develops over time
Lorazepam trade name
Ativan
Ativan potency (comp)
More potent compared to other BZDs.
Ativan solubility
Insoluble in water
Requires polyethylene glycol = burns on injection
Ativan onset (comp) and peak
Slower onset than versed and Valium
Peak: 20-30 min with 1-4mg IV dose
Ativan E 1/2 time
14 hours.
Ativan metabolism
Conjugated to inactive metabolites
Less dependent on hepatic enzymes
Ativan dose
1-4 mg IV.
Flumazenil trade name
Romazicon.
Flumazenil MOA
Competitive antagonist for BZD receptor.
Flumazenil metabolism
Hepatic Microsomal enzymes.
Flumazenil dose
0.2 mg IV
Repeat 0.1 mg q1 min
max 1 mg total to consciousness
Flumazenil duration
30-60 min (shorter than BZD => resedation from BZD).
Flumazenil side effects
No significant side effects.
Flumazenil contraindication
Contraindicated in pt taking antiepileptic drugs.
