RE Ch 9 Flashcards by Lindsay Gatza

The time to awakening following a single dose of propofol is generally how long?

5-15 minutes

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An open vial of propofol is good for how long?

12 hours, or 6 hours if transferred from its original container- like in a syringe

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True or False: Metabolism of propofol plays the biggest role in initial awakening of the patient, but little in the eventual clearance of the drug.

FALSE
Metabolism plays little role in the initial awakening
Metabolism IS important in the eventual clearance of the drug

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True or False. Propofol has rapid metabolic clearance which actually exceeds hepatic blood flow.

TRUE

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Why might you see no change in elimination for patients with severe cirrhosis?

Likely due to extrahepatic sites of metabolism

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What percent of propofol is excreted unchanged?

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which enzyme is not responsible for the metabolism of propofol
CYP2B6
UGTHP4
CYP2C6
CYP450

CYP450

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While the dose of propofol is decreased for the elderly, why is it increased for children?

they have an increased volume of distribution based on body weight and their rate of clearance is also higher

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The elimination half life of propofol is how long

1-2 hours

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Propofol reversibly binds to _____________ (50%) and _________ (48%) which makes the free concentration less than 2%.

erythrocytes
plasma proteins (most commonly plasma albumin)

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Define decrement time

time from the end of the infusion to 50% recovery and includes pharmacokinetic data related to concentration decrease and pharmacodynamic data correlating with recovery.

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Three scenarios that may increase the level of free active fraction

third trimester pregnancy
kidney failure
liver failure
all cause decreased plasma protein levels

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The GABAa receptor where propofol works is what type of receptor

Ligand-gated ion channel receptor is activated by binding of the neurotransmitter GABA

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The binding of GABA to GABAa receptors initiates the movement of what ion through ion channels into the cell?

chloride

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The movement of chloride into the cell results in what?

hypopolarization of postsynaptic cell membrane and the inhibition of neuronal cell excitation.

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True or false: propofol both directly stimulates GABAa receptors AND potentiates the actions of endogenous GABA.

TRUE

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Name 4 dose dependent physiologic reductions that occur with propofol infusions.

CBF
CMRO2
ICP
CPP

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True or False: Cerebral auto-regulation and reactivity to changes in CO2 are preserved with propofol.

True

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propofol causes cerebral vasodilation or constriction?

vasoconstriction (pg 107)

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Propofol may cause insignificant hypotension in healthy adults and children. Predictors of hypotension with propofol induction are….

age greater than 50
ASA class 3 or 4
baseline MAP less than 70
coadministration with high dose fentanyl

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List the factors from table 9-3 that alter protein binding
Increase binding:
Decrease binding:

Increase: increased pH >8.0, Increased protein concentration

Decrease: Decreased lipid solubility, Increased drug concentration, Increased competition for binding sites with other drugs

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Propofol induced hypotension results from a combination of….

WHAT ARE THE PRIMARY REASONS?

a combination of CNS,cardiac, and baroreceptor depression, as well as decreases in sympathetic tone and systemic vasodilation

PRIMARY- DECREASED SYMPATHETIC TONE AND VASODILATION

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Can propofol be used in cardiac anesthesia?

Yes, but with a decreased dose

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With propfol administration- which is greater….decrease in tidal volume or decrease in resp rate?

Tidal volume. although apnea is common with initial or induction dose

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Does propofol cause histamine release?

which anesthetic agent is NOT a preferred induction agent for a patient with asthma? Propofol Ketamine Etomidate

Etomidate

Does propofol cross the placenta in pregnant women? give rationale

Yes, propofol is highly lipid soluble and therefore DOES cross the placenta often leading to neonate sedation and lower apgar scores

what is the ph and pka of etomidate

8.1 and 4.2

advantages and disadvantages of etomidate

no cardiac or respiratory effects nausea, vomiting, pain with injection, no analgesia, adrenocortical suppression, myoclonia

Induction dose of etomidate

0.2-0.3 mg/kg

How is etomidate metabolized?

rapidly metabolized by the liver by hepatic microsomal enzymes and plasma esterases

what is the primary mode of metabolism of etomidate

ester hydrolysis in liver and plasma

etomidate is eliminated where?

10% bile 13% feces remainder kidneys

T or F rapid metabolism accounts for etomidates extremely short duration of action?

F- Rapid Redistribution accounts for extremely short DOA

etomidate is or is not lipid soluble?

it IS lipid soluble so within a minute of administration brain levels rise rapidly.

What is the hepatic extraction ratio of etomidate? | what is the terminal half life

67% | 2-5 hours

describe etomidates protein binding

76% protein bound, mostly to albumin

two factors that may compensate for changes in protein binding of etomidate?

metabolism and elimination

What is the MOA of etomidate?

GABA modulation

Cerebral blood flow and CMRO2 are increased or decreased by etomidate?

decreased

etomidate will increase or decrease intraocular pressure

decrease

pretreatment with which drugs may reduce the incidence of etomidate induced myclonia?

precedex, roc, lidocaine, midaz, or a small dose of etomidate prior to the induction dose.

which population is likely to have a significant decrease in sbp, pap, and pcwp following etomidate administration.

pts with aortic and mitral valve disease

describe the dose dependent changes seen with etomidate in regards to minute ventilation and respiratory rate

Ve decreases | RR increases

The ventilatory response to CO2 following etomidate administration is increased, decreased, or unchanged?

decreased

Enzymes inhibited responsible for the adrenocortical suppression seen with etomidate induction

The P450 dependent enzymes and 11B-hydroxylase

The inhibition of those enzymes results in an increase in _______ and decrease in ________.

cortisol precursors | cortisol, aldosterone, and corticosterone levels

solvent that causes pain and phlebitis on injection of etomidate

propylene glycol

3 contraindications of etomidate

known sensitivity adrenal suppression acute porphyrias

induction agents safe to use with patients with acute porphyria

propofol | ketamine

MOA of etomidate appears to be

GABA-mimetic

Due to the inhibition of 11B-hydroxylase which is required for the production of both corticosteroids and mineralocorticoids clinically significant reduction in ___________ may result from using etomidate both single dose and infusion

steroid production

Etomidate increases or decreases PONV

INCREASES

Name a drug that can be very useful in anesthesia and sedation of high risk, pediatric, and asthmatic patients

ketamine

pH and PKA of ketamine

pH 3.5-5.5 | pka 7.5

MOA of ketamine

antagonism of the NMDA receptors in the brain.

antagonism of NMDA receptors on the brain results in.....

selective depressant effect on the medial thalamic nuclei that is responsible for blocking afferent signals of pain perception to the thalamus and cortex

Where is the primary site of analgesic action of ketamine

thalamoneocortical system

How does the NMDA receptor work?

NMDA receptor is a ligand-gated ion channel where Ca+ and Na+ are voltage dependent.

Name the amino acid that is probably the most important excitatory neurotransmitter in the CNS

L-glutamate

Is ketamine a competitive or noncompetitive antagonist at the NMDA receptor?

noncompetitive

T or F Ketamine induced analgesia has a spinal cord component.

True

describe the metabolism of ketamine

metabolism by the cytochrome P450 system is demethylation to form norketamine

elimination of ketamine is primarily

renal

T or F. The distribution kinetics of ketamine follows a two compartment model?

true

The onset of a standard 2-2.5 mg/kg dose of ketamine has a faster or slower onset than propofol or etomidate

slower. 3-5 mins

Why does ketamine have a slow elimination half life?

hepatic metabolism and excretion. A large amount of ketamine remains in the peripheral tissues as active drug and may be responsible for prolonged cumulative effects.

what is the elimination half life of ketamine

2-3 hours

Ketamine elimination is dependent or independent of hepatic blood flow?

dependent- the mean total body clearance is approximately the same as the hepatic blood flow

Is distribution of ketamine dose dependent?

No (pg 114) | So that implies zero order kinetics????

Which routes are available for ketamine administration? Which route has 93% bioavailability?

Oral IM IV IM is 93% bioavailable

Skeletal muscle tone increases or decreases with ketamine administration?

increases. muscle movements may occur unrelated to painful stimulus

T or F. As with other IV induction agents, ketamine causes a decrease in CBF, CMRO2, and ICP

False, Increased

Describe EEG changes you would expect when a pt loses consciousness as a result of Ketamine

transition from alpha to theta waves

T or F Ketamine does not alter auditory evoked potentials

True

Describe Ketamines effects on bp, hr, contractility, CO, CVP

all increased

Injection of ketamine into the CNS causes an enhancement or inhibition of norepi uptake?

inhibits neuronal and extraneuronal uptake of norepi

who may experience negative inotropic effects from ketamine?

critically ill with depleted catecholamine stores

T or F- inhaled anesthetics may cause Ketamine to lower bp and CO

true- due to the decreasing sympathetic responses

What ophthalmic changes are seen with ketamine?

increased IOP and nystagmus

ketamine causes bronchodilation or constriction?

potent bronchodilator

T or F. With ketamine administration central response to CO2 is maintained.

True

Which antisalagogue is considered superior for administration with ketamine?

atropine (p116)

ketamine is/is not highly lipid soluble...does/does not cross placenta?

IS highly lipid soluble and therefore does cross the placenta

how do you use ketamine safely in obstetrics?

decreasing the dose to 0.2-1 mg/kg spares the neonate sedation issues

ketamine may be the agent of choice in which peds populations?

difficult airway and reactive airway

what structure is unique to midazolam vs other benzos

the imidazole ring

T or F. midazolam is lipid soluble at pH less than 4.0

False, water soluble and does not require a lipoidal vehicle such as propylene glycol

What happens to midaz in a physiologic pH greater than 4.0?

the diazepine ring closes and midaz becomes lipophilic which accounts for its rapid onset of action

benzo MOA

agonist action at benzo receptor binding sites on the GABAa receptors throughout the CNS

Of the three classes of ligands that bind to benzo receptors (agonists, antagonists, and inverse agonists)...midaz, diazepam, loraz would be considered ______?

agonists- increase binding affinity for GABA- resulting in opening of chloride channels, resulting in post synaptic membrane hyperpolarization- inhibiting neuronal transmission

Give an example of a ligand that would be an antagonist at the benzo receptor

Flumazenil- forms a reversible bond with the agonist receptor but produces no agonist activity.

Name an example of a long, intermediate, and short acting benzo

long diazepma intermediate loraz short midaz

what is the T1/2 of midaz

less than 6 hours

benzos are terminated by

redistribution out of the CNS

of the 3 IV benzos...which is less dependent on hepatic cytochrome enzymes for metabolism? why?

lorazepam. it undergoes phase 2 conjugation to a significant extent. liver disease as well as hepatic enzyme induction or inhibition does not influence loraz as much as other drugs

benzos- Volume of distribution- large or small? | protein binding- limited or extensive?

large | extensive

which benzo may be useful in preventing chemo induced nausea and vomiting?

loraz

benzos increase or decrease the threshold local anesthetic induced seizure activity

increase

EEG changes associated with benzos

alpha disappears, beta activity is seen

which benzo causes the most respiratory depression

midaz

which patient population should avoid benzos

acute porphyrias

flumazenil is a competitive or noncompetitive antagonist?

competitive

onset and duration of flumazenil

1-2 mins, 45-90 mins

flumazenil is contraindicated in whom?

pts with known history of seizures | pts who are benzo dependent and experience withdrawal

MOA for precedex

selective alpha 2 agonist

what accounts for the hypotensive side effects seen with precedeX

stimulation of imidazoline receptors

when alpha 2 receptors are stimulated by an agonist what results?

decreased catecholamine release

what is the main site of action for the sedative effects of precedex?

the pontine noradrenergic nucleus the locus coeruleus

The alpha 2 receptors are what type of receptor?

G-protein coupled receptors

When the G protein coupled receptors are activated....the result is activated or inhibited Ca+ channels, potassium channels?

inbibited Ca+, activated K, and direct modulation of exocytic release of proteins

state the loading dose and infusion rate of precedex

1 mcg/kg over 10 mins, then 0.2-0.7 mcg/kg/HR

T or F precedex is protein bound and undergoes almost complete biotransformation leaving very little unchanged in the urine and feces

True

biotransformation of precedex involves....

direct glucuronidation | cytochrome P450-mediated metabolism

Precedex causes increased, decreased, or unchanged CMRO2

unchanged

Precedex is a drug of choice for what specific procedures?

procedures requiring a wake up test

precedex does or does not interfere with electrophysiologic monitoring

does not. useful for brain mapping

Effects of precedex on CBF

decreased due to vasoconstriction

precedex analgesia and anesthetic effects work at what levels?

brain and spinal cord

precedex enhances the analgesic effect of _______

N2O

Main CV effects seen with precedex?

bradycardia and hypotension

why does precedex cause hypoTN and bradycardia?

CNS alpha receptor stimulation and systemic vasodilation

T or F- precedex does not interfere with neuro monitoring

true

T or F: precedex is an alpha 2 agonist that results in central sympatholysis

TRUE

Who should generic propofol be used in caution with?

Metabisulfite - allergy or asthma Benzoyl alcohol - avoided in infants

RE Ch 9 Flashcards

(125 cards)