Benzos (Ex1) Flashcards by Andrew Everett

Sedative/hypnotics definition

Drug that induces sleep, calm or hypnosis

Used fairly interchangeable

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How is EEG monitoring used to measure drug effects

Anesthesia alters CBF and CMRO2
-CBF and CMRO2 relate to EEG activity

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BIS monitoring explanation

Processed EEG compacted into one waveform
Helps determine level of sedation/consciousness

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BIS # showing unconsciousness

Less than 58

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BIS # less than 65

5% chance of consciousness within 50 seconds

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SQI on BIS monitor

Signal quality index
-measures quality or lack of interference

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SR on BIS monitor

Suppression Ratio
-number of times EEG flatlined

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Examples of BIS suppressants (5)

Hypnotics, volatiles, NMBD, opioids, beta blockers

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Examples of BIS stimulants (2)

Ketamine
Epinephrine

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Ideal range for BIS# general anesthesia

40-60

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Pharmacologic effects of BZDs (5)

-Anxiolytic
-Sedation
-Anterograde amnesia (forward)
-Anticonvulsant
-Skeletal muscle relaxation (not paralysis)

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BZD benefit over barbiturates (3)

-Less tolerance or abuse potential
-Fewer/less severe side effects
-Don’t induce CYP450

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BZD MOA

Facilitates actions of GABA-A => enhanced open of chloride channels => hyperpolarization of postsynaptic membrane

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GABA alpha-1 effects (3)

Sedative
Amnesia
Anticonvulsant

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GABA alpha-2 effects (2)

Anxiolytic
Skeletel muscle relaxation

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Synergistic drugs also acting on GABA-A (4)

Barbiturates
Etomidate
Propofol
Alcohol

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BZD EEG effects (2)

-Decrease alpha wave activity => relaxation
-Some able to flattened brain waves

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Midazolam trade name

Versed

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Versed amnesia vs sedation effects

Amnestic effects last longer than sedation effects

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Versed solubility with pH

In less than 3.5 pH => water soluble (ring open)

In more than 4 pH => lipid soluble (ring closed)

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Versed onset and peak effect

Onset: 1-2 min
Peak: 5 min

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Versed protein binding

Extensively bound 96-98%

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BZD reversal drug

Flumazenil (Romazicon)

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Versed E 1/2 time

2 hours
Doubled in elderly pts

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Versed Vd

Large

Versed metabolism

CYP3A4 (hepatic Microsomal enzymes)

Significant Drugs that can decrease BZD metabolism by CYP inhibition (3)

Cimetidine (Tagamet) Calcium channel blockers Fentanyl

Versed cerebral flow effects

Decrease CMRO2 Decrease CBF (Both dose related)

Versed EEG effects

-Potential anticonvulsant -Unable to produce isoelectric EEG (flatline)

CO2 cerebral flow effects

High CO2 => cerebral vasodilation Low CO2 => cerebral vasoconstriction

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

Versed Postoperative sedation dose

1-7 mg/hr IV Not recommended for use more than 2 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)

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 Slight decrease in Vt

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

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 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 -prevents/reverses BZD agonist activity

Flumazenil metabolism

Hepatic Microsomal enzymes

Flumazenil dose

0.2 mg IV -repeat 0.1 mg q1 min to 1 mg total To consciousness

Flumazenil duration

30-60 min (shorter than BZD => resedation from BZD)

Flumazenil side effects

No significant side effects

Flumazenil cautions

Contraindicated in pt taking antiepileptic drugs