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BASIC EXAM Part I | Question Bank > PHARMACOLOGY | IV Anesthetics Part I > Flashcards

PHARMACOLOGY | IV Anesthetics Part I Flashcards

1
Q

This is defined as the time to achieve a 50% reduction in concentration after stopping a continuous infusion:

A. Context-sensitive halftime

B. Elimination half-life

C. Bioavailability

A

A. Context-sensitive halftime

Reduction in concentration AFTER stopping the CONTINUOUS infusion

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2
Q

The following are pharmoco-properties IDEAL for IV anesthetics EXCEPT:

A. It should be water-soluble and stable

B. No tissue damage with extravasation

C. Low incidence of histamine release or hypersensitivity

D. Slow onset and predictable duration

E. Rapid metabolism to inactive metabolites

A

D. Slow onset and predictable duration - False statement

ideally it must be fast onset!

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3
Q

Which of the following is MOST accurate regarding the IV anesthetic and its effect on the CNS?

A. GABA is the primary excitatory neurotransmitter in CNS

B. Activation of GABA causes increase in chloride conductance, and therefore hyperpolarization of neuron

C. Benzodiazepines decreases the frequency of chloride channel openings

D. glutamate, glycine, and D-serine are major inhibitory neurotransmitter

A

B. Activation of GABA causes increase in chloride conductance, and therefore hyperpolarization of neuron

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4
Q

Which of the following is MOST accurate regarding the clinical effects of Propofol:

A. It can produce bronchodilation in patients with
COPD

B. Propofol inhibits pulmonary vasoconstriction

C. It does not exhibit myoclonus like that of thiopental

D. Fospropofol is a prodrug of Propofol which has a faster onset and longer duration

A

A. It can produce bronchodilation in patients with
COPD

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5
Q

This is the time it takes for the plasma concentration of a drug to decrease to 50% of its
original concentration:

A. Context-sensitive halftime

B. Elimination half-life

C. Bioavailability

D. Volume of distribution

A

B. Elimination half-life

This concept works well to describe a one compartment model for a drug distributed only to the blood, or if the drug is administered only once.

In contrast, pharmacokinetic modeling that describes intravenous anesthetics administered by infusion needs to account for multiple compartments, phases of distribution, and elimination.

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6
Q

TRUE or FALSE

Thiopental has a LOWER context-sensitive half-time compared to Propofol.

A

FALSE

In comparison to thiopental, propofol has a much lower context-sensitive half-time. Although, the elimination of propofol is prolonged with longer infusions, it is not to the same magnitude as with thiopental.

It is the low context-sensitive half-time that allows for propofol to be used as a continuous infusion.

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7
Q

Which of the following is MOST accurate regarding the pharmacodynamic of Propofol?

A. a state of paradoxical excitation is expected at the start of low dose

B. it acts primarily via inhibition of gamma-aminobutyric acid-A (GABA-A) pathways

C. Propofol binds post-synaptically and enhances GABA-nergic inhibition

D. Burst suppression is not expected even with low dose

A

C. Propofol binds post-synaptically and enhances GABA-nergic inhibition

  • The mechanism by which the unconscious state is attained by Propofol is complicated, but primarily occurs via enhancement
    of gamma-aminobutyric acid (GABA) inhibitory pathways.
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8
Q

TRUE or FALSE

The rapid onset of ETOMIDATE is due to high lipid solubility and large non-ionized fraction at physiologic pH

A

TRUE

Non-ionized = RAPID onset
High lipid solubility = RAPID onset

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9
Q

TRUE or FALSE

Propofol shortens seizure duration

A

TRUE

It has also been used successfully to treat status epilepticus, thus it is rarely the anesthetic of choice during induction of anesthesia for electroconvulsive therapy (ECT) because it SHORTENS seizure duration.

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10
Q

TRUE or FALSE

The loss of consciousness attributed to propofol can be partially reversed physostigmine.

A

TRUE

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11
Q

The effects of ketamine related to pain can be best described as:

A. antihyperalgesic, antiallodynic, or tolerance protective

B. antihyperalgesic only

C. antiallodynic but NOT tolerance protective

A

A. antihyperalgesic, antiallodynic, or tolerance protective

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12
Q

Which of the following statement is ACCURATE in terms of the pharmaco-property of Ketamine:

A. Ketamine is a racemic mixture and R(-) is more potent than S(+)

B. Ketamine is secreted in the urine with a half-life of 2-3 hrs

C. Ketamine has high protein binding

D. Norketamine is the metabolite of ketamine and has no effect

A

B. Ketamine is secreted in the urine with a half-life of 2-3 hrs - TRUE statement

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13
Q

Which form of KETAMINE is more potent?

A. S(+) enantiomer

B. R(+) enantiomer

A

A. S(+) enantiomer

MORE potent, SHORTER duration, cleared RAPIDLY

The S(+) enantiomer of ketamine is three to four times more potent than the R enantiomer. The S enantiomer has a shorter duration of action and is cleared more rapidly.

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14
Q

Why is it needed to decrease the DOSE of ketamine in patients with severe critical illness?

A

Ketamine has INTRINSIC myocardial depressant hence, in severely ill patients with DEPLETED catecholamine reserves, it is crucial to lower the dose to minimize the myocardial depressant effect!

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15
Q

Which is MOST accurate regarding KETAMINE:

A. Ketamine is a racemic mixture and the R(-) enantiomer is considered more potent than S(+)

B. Norketamine is eliminated primarily by hepatobiliary excretion

C. Ketamine has poor protein binding

D. Norketamine is the metabolite of ketamine and has no clinical effect

A

C. Ketamine has poor protein binding

The high lipid solubility and low protein binding (20%) allow for a rapid uptake of ketamine in the brain, as well as a fairly rapid redistribution.

ONSET: 15 - 30 seconds

DURATION: 10 - 15 minutes

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16
Q

Benzodiazepines act on GABA-A and produce a net effect by:

A. Increase in Cl conductance

B. Decrease in Cl conductance

C. Increases duration of Cl channel opening

D. Decreases duration of Cl channel opening

A

A. Increase in Cl conductance

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17
Q

The mechanism of action of Barbiturates on Cl channel is:

A. Increase duration of chloride channel opening

B. Decrease duration of chloride channel opening

C. Increase Cl conductance

D. Decrease Cl conductance

A

A. Increase duration of chloride channel opening

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18
Q

The sense of well being “euphoria” from Propofol is primarily attributed to:

A. Increase of Dopamine in NUCLEUS ACCUMBENS

B. Decrease of Dopamine in NUCLEUS ACCMBENS

C. GABA-B potentiation

A

A. Increase of Dopamine in NUCLEUS ACCUMBENS

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19
Q

After a single bolus of PROPOFOL, the plasma level decreases immediately thru:

A. Redistribution

B. Extrahepatic clearance

A

A. Redistribution

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20
Q

Propofol increases the duration of action of Midazolam. This is due to which mechanism?

A. Competitive inhibition of CYP3A4

B. Extrahepatic metabolism of propofol

C. Decrease dopamine in the nucleus accumbens

A

A. Competitive inhibition of CYP3A4

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21
Q

If propofol is administered via continuous IV infusion for 3 - 8 hours, it’s context-sensitive half-time will be:

A. 40 mins

B. 10 mins

C. 1 hour

D. 2 hours

A

A. 40 mins

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22
Q

What is the effect of HYPOTENSION to the clearance of Propofol?

A
  • Decrease CO > Decrease liver blood flow > reduce the rate of clearance > therefore, it PROLONGS the duration of ACTION
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23
Q

TRUE or FALSE

Propofol decreases CPP but NO EFFECT on cerebral autoregulation?

A

TRUE

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24
Q

At a maintenance rate, Propofol infusion will have the following effect on lung mechanics?

A. Decrease RR

B. Increase RR

C. Increase TV

A

B. Increase RR

During induction dose, a single bolus of PROPOFOL will have a dose-dependent APNEA however, with continuous IV infusion, RR will have a 20& increase and TV will decrease.

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25
Q

Induction dose of Propofol is based on?

A. actual body weight

B. total body weight

C. lean body weight

A

C. lean body weight

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26
Q

Propofol produces a dose-dependent decrease in blood pressure without compensatory elevation of the heart rate (tachycardia). This is due to:

A. Inhibition of baroreceptor reflex

B. Inhibition of chemo receptor

C. Bainbridge reflex

A

A. Inhibition of baroreceptor reflex

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27
Q

Propofol Infusion Syndrome is highly associated with this plasma dose:

A. >70 mcg/kg.min

B. >50 mcg/kg/min

C. >30 mcg/kg/min

A

A. >70 mcg/kg.min

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28
Q

The most apparent effect of Propofol on SSEP monitoring:

A. Increase latency, decrease amplitude
B. Decrease latency, decrease amplitude
C. Increase latency, Increase amplitude

A

A. Increase latency, decrease amplitude

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29
Q

TRUE or FASLE

Propofol SUPPRESS atrial tachycardia

A

TRUE!

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30
Q

The most common extra-hepatic elimination of Propofol is thru:

A. Lungs
B. Kidney
C. Heart
D. Esterases

A

A. Lungs

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31
Q

Comparing the induction dose of thiopental vs propofol, an inducting dose of propofol produces:

A. Better maintenance of cerebral perfusion pressure

B. Greater inhibition of glucocorticoid production

C. Higher incidence of myoclonus

D. Less severe hypotension

E. Less severe respiratory depression

A

C) Higher incidence of myoclonus

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32
Q

Which of following is known effect of propofol?

A. Decrease amplitude of SSEP

B. Induces malignant hyperthermia

C. Inhibition of cytochrome p450

D. Initiation of porphyria

E. Inhibition of glucocorticoid function

A

A. Decrease amplitude of SSEP - Correct answer

B. Induces malignant hyperthermia - (volatiles, succinylcholine)

C. Inhibition of cytochrome p450 - (several, but not propofol)

D. Initiation of porphyria - (variety of drugs, but not propofol)

E. Inhibition of glucocorticoid function - this is etomidate

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33
Q

TRUE or FALSE

Propofol significantly inhibits hypoxic pulmonary vasoconstriction

A

FALSE!

Does not INHIBIT HPV.

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34
Q

TRUE or FALSE

The unconsciousness attained by PROPOFOL is thru inhibition of GABA pathways.

A

FALSE!

The mechanism by which the unconscious state is attained by Propofol is complicated, but primarily occurs via enhancement
of gamma-aminobutyric acid (GABA) inhibitory pathways.

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35
Q

Components of PROPOFOL except:

A. 2.5% glycerol
B. 1.2 % egg phospholipid
C. 10 % soybean oil
D. EDTA
E. 10% Propofol

A

E. 10% Propofol - only 1% of PROPOFOL!

PROPOFOL consists:

1% propofol
1.2% egg phospholipid
2.25% glycerol
10% soybean oil
emulsifier
ethylenediamenetetraacetic acid (EDTA)

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36
Q

TRUE or FALSE

Propofol binds pre-synaptically and enhances GABAergic inhibition.

A

FALSE!

Propofol binds post-synaptically and enhances GABAergic inhibition.

Unconsciousness occurs as this enhanced GABAergic inhibition counteracts
ascending arousal inputs to the pyramidal neuron and decreases excitatory activity.

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37
Q

EEG activity tracing with the induction dose of PROPOFOL:

A. increase in alpha and delta activity

B. beta-wave activity is dominant

C. decrease both aplha and delta activity

A

A. increase in alpha and delta activity

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38
Q

Plasma concentrations needed to reach the initial stages of general anesthesia with PROPOFOL:

A. 3 mcg/mL

B. 8 mcg/mL

C. 5 mcg/mL

A

A. 3 mcg/mL

8 mcg/mL - BURST SUPRESSION is achieved with this plasma level

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39
Q

TRUE or FALSE

Propofol has specific antioxidant properties

A

TRUE

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40
Q

Why is Propofol not an ideal agent for ECT?

A. It shortens the duration of seizure

B. It arrests the seizure threshold

C. It lengthens the duration of seizure

A
  • It shortens the duration of seizure

It has also been used successfully to treat status epilepticus, thus it is rarely the anesthetic of choice during induction of anesthesia for electroconvulsive therapy (ECT) because it shortens seizure duration.

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41
Q

TRUE or FALSE

Loss of consciousness by PROPOFOL can be partially reversed by Physostigmine.

A

TRUE

The loss of consciousness attributed to Propofol can be partially reversed by the central cholinomimetic properties of physostigmine

42
Q

Chronic Alcohol intake will need a ___ inducting dose of Propofol:

A. increase

B. decrease

A

Increased

  • Patients with chronic alcohol abuse, as expected, have an increased induction dose
    requirement.

Morbidly obese patients should have lean body weight used when calculating propofol dosing.

  • An exaggerated hemodynamic response is likely after induction of propofol in patients with cardiovascular disease.
43
Q

Which of the following is NOT a direct central nervous system effect of propofol?

(A) GABAA receptor activation in the hippocampus

(B) widespread NMDA glutamate receptor inhibition

(C) decreased serotonin levels in the area postrema

(D) activation of glycine-gated chloride channels in the spinal cord

(E) activation of α-2 adrenergic receptors in the locus ceruleus

A

(E) activation o α 2 adrenergic receptors in the locus ceruleus

44
Q

Patients with Myasthenia Gravis are sensitive to ____

A. Nondepolarizing muscle relaxant

B. Depolarizing muscle relaxant

A

A. Nondepolarizing muscle relaxant

45
Q

Patients with Myasthenia Gravis are resistant to ____

A. Nondepolarizing muscle relaxant

B. Depolarizing muscle relaxant

A

B. Depolarizing muscle relaxant

46
Q

The incidence of unpleasant dreams associated with emergence from ketamine anesthesia can be reduced by the administration of

A. Caffeine
B. Droperidol
C. Physostigmine
D. Midazolam

A

D. Midazolam

47
Q

Hyperkalemia is NOT a risk for patients receiving succinylcholine with which of the following?

A. Multiple sclerosis (MS)
B. Myasthenia gravis
C. Guillain-Barré syndrome
D. Becker muscular dystrophy

A

B. Myasthenia gravis

48
Q

Which of the antibiotics below does NOT augment neuromuscular blockade?

A. Clindamycin
B. Neomycin
C. Streptomycin
D. Erythromycin

A

D. Erythromycin

49
Q

A 37-year-old patient with a history of acute intermittent porphyria is scheduled for knee arthroscopy under general anesthesia. Which of the following drugs is contraindicated in this patient?

A. Fentanyl
B. Isoflurane
C. Propofol
D. Etomidate

A

D. Etomidate

50
Q

The most important reason for the more rapid onset and shorter duration of
action of FENTANYL with single dose compared with MORPHINE is the difference in:

A. Volume of distribution
B. Hepatic clearance
C. Protein binding
D. Lipid solubility

A

D. Lipid solubility

51
Q

TRUE or FALSE

Infant and children requires a higher dose of Propofol compared with adults.

A

TRUE

On the opposite end of the spectrum, children typically have a larger than average volume of distribution and quicker clearance, resulting in increased Propofol
requirement on a per-kilogram basis.

Barash | 9th edit

52
Q

The pathologic reason why PRIS happens?

A

Primarily because of mitochondrial toxicity and uncoupling of the intracellular respiration chain.

53
Q

The most common reason for patients to rate anesthesia with etomidate as unsatisfactory is:

A. PONV
B. Pain on injection
C. Recall of intubation
D. Postoperative hiccups

A

A. PONV

54
Q

Which of the following pharmacokinetic property of ETOMIDATE is FALSE?

A. It has imidazole derivative and unstable in neutral pH solution

B. the content propylene glycol contributes to the veno-irritation and phlebitis

C. excreted predominantly by the bile

D. Conditions with low serum proteins can alter the effect of etomidate

A

C. excreted predominantly by the bile - FALSE statement

Etomidate is metabolized in the liver and excreted predominantly by the kidney (approximately 80%) and in bile (approximately 20%).

It is largely protein bound (approximately 75%) and thus affected by pathologic conditions and/or drugs that alter serum proteins.

55
Q

Etomidate has a low induction dose of 0.2 - 0.3 with a very rapid onset. This is due to:

A. High lipid solubility, non-ionized fraction at physiologic pH

B. High lipid solubility, ionized fraction at physiologic pH

A

A. High lipid solubility, non-ionized fraction at physiologic pH

56
Q

Which of the metabolic pathway of cortisol does inhibition by Etomidate takes place?

A. Deocortisol > cortisol

B. Progesterone > 11-deoxycorticosterone

C. 11-deoxycortisol > Cortisol

D. Corticosterone > Aldosterone

A

C. 11-deoxycortisol > Cortisol

57
Q

Etomidate hemodynamic effects are the following EXCEPT:

A. relaxes the smooth musculature of the pulmonary vasculature system

B. Increases the PA wedge pressure

C. Negligible effect on cardiac index

D. minimal effect on SVR

A

B. Increases the PA wedge pressure - FALSE

Why?

  • Etomidate has a nonexistent effect on MAP, pulmonary artery (PA) pressure, PA wedge pressure, central venous pressure (CVP), stroke volume, cardiac index, SVR, and pulmonary vascular resistance (PVR).
  • Etomidate is a reasonable choice for MAC sedation because of the preservation of airway reflexes.
58
Q

Etomidate is similar with Ketamine in which physiologic effect?

A. preservation of airway reflexes

B. Increase in SVR

C. Analgesia

D. Onset of hypnosis

A
  • Etomidate is a reasonable choice for MAC sedation because of the preservation of airway reflexes.
59
Q

The most important clinical adverse effect of Etomidate is:

A. PONV

B. veno-irritation

C. adrenocortical suppression

A

C. adrenocortical suppression

Adrenocortical suppression may be the most significant adverse effect of etomidate.

Etomidate inhibits the activity of the enzyme 11-beta-hydroxylase and prevents the conversion of cholesterol to cortisol.

  • Cholesterol to cortisol is inhibited.
60
Q

Which of the following best describes the effect of an
induction dose of etomidate on the central nervous
system?

(A) a decrease in CMRO2, a decrease in CBF, and a decrease in CPP

(B) a decrease in CMRO2, an increase in CBF, and a decrease in CPP

(C) a decrease in CMRO2, a decrease in CBF, and an increase in CPP

(D) an increase in CMRO2 , a decrease in CBF, and a decrease in CPP

(E) an increase in CMRO2 , an increase in CBF, and
a decrease in CPP

A

(C) a decrease in CMRO2, a decrease in CBF, and an increase in CPP

An induction dose of etomidate (0.2–0.4 mg/kg)
reduces both cerebral blood flow and CMRO2 by
30–45%. Etomidate also reduces elevated ICP, but unlike induction doses of propofol or thiopental, MAP is preserved without the need or additional vasopressor therapy.

As a result, cerebral perfusion pressure is increased (CPP = MAP – ICP), and there is a beneficial net increase in the cerebral oxygen supply-demand ratio.

Etomidate is an appropriate agent to use for induction and maintenance o anesthesia during most neurosurgical procedures.

Keyword: DECREASE CMRO2, CBF but INCREASE CPP

61
Q

Which of the following is NOT associated with the use
of etomidate?

(A) grand mal seizures

(B) decreased latency o somatosensory evoked
potentials

(C) the absence o beta waves on EEG

(D) disruption of intraoperative mapping of
seizure foci

(E) increased amplitude o somatosensory evoked
potentials

A

(D) disruption of intraoperative mapping of
seizure foci

62
Q

Which of the following best describes the effect of an
induction dose of etomidate on the endocrine system?

(A) a dose-dependent, reversible inhibition of the
enzyme 11β -hydroxylase

(B) a dose-dependent, reversible inhibition of the
enzyme tyrosine hydroxylase

(C) a dose-dependent, reversible inhibition of
the enzyme catechol-O-methyltransferase

(D) a dose-dependent, reversible inhibition of the
enzyme 5α -reductase

(E) a dose-dependent, reversible inhibition of the
enzyme aldosterone synthase

A

(A) a dose-dependent, reversible inhibition of the
enzyme 11β -hydroxylase

63
Q

Which of the following intravenous anesthetic agents is associated with the highest incidence of nausea and vomiting?

A. Midazolam
B. Etomidate
C. Ketamine
D. Propofol

A

B. Etomidate

Etomidate has the highest incidence of nausea and vomiting, with reports as high as 40%

64
Q

A patient being mechanically ventilated in the ICU requires wound debridement twice daily. Each of the following agents would be appropriate for induction of brief general anesthesia EXCEPT:

(A) nitrous oxide
(B) etomidate
(C) ketamine
(D) methohexital
(E) midazolam

A

(B) etomidate

Even a single bolus of etomidate can cause adrenal suppression which is not beneficial for a critically ill patient.

65
Q

Which of the following is NOT a reported side effect
of etomidate?

(A) nausea and vomiting
(B) increased intraocular pressure
(C) superficial thrombophlebitis
(D) myoclonic movements
(E) pain on injection

A

(B) increased intraocular pressure

66
Q

TRUE or FALSE

Etomidate does not precipitate in intravenous lines.

A

Etomidate does not precipitate in intravenous lines
(unlike thiopental, which does in the presence o solutions
with low pH).

67
Q

What is the mechanism of action of midazolam at the
GABA-A receptor?

(A) direct activation of the GABA-A receptor and increased chloride conductance

(B) direct activation of the GABA-A receptor and increased potassium conductance

(C) competitive inhibition at the acetylcholine
binding site

(D) allosteric modulation of GABA binding to
GABA-A receptor

(E) increased transmembrane sodium conductance

A

(D) Allosteric modulation o GABA binding to
GABA-A receptor

Midazolam (and other benzodiazepines) act at the
benzodiazepine receptor on the GABA-A receptor
complex. The binding of midazolam results in increased binding affinity of GABA or the GABA-A receptor (allosteric modulation).

  • GABA-A activation causes influx of chloride ions and hyperpolarization of the cell membrane. Direct activation of the GABA-A receptor can occur with barbiturates and etomidate.

NMDA receptor activation alters sodium and potassium
conductance. Barbiturates such as thiopental are
also thought to act as a competitive inhibitors at CNS
acetylcholine (and glutamate) receptors.

68
Q

TRUE or FALSE

Midazolam can be given via intranasal route.

A

TRUE

Midazolam can be administered intravenously, intranasally, orally, rectally, and intramuscularly. This flexibility in route of administration also contributes to its popularity

69
Q

Which of the following is INACCURATE in terms of the pharmacodynamic of benzodiazepine?

A. High protein binding renders a smaller free fraction of the drug available to cross the blood–brain barrier

B. High lipophilicity results in a significantly smaller volume of distribution

C. Midazolam is a safe drug for continuous infusion

D. Drugs that inhibit the cytochrome P450 system prolongs the duration of benzodiazepine

A

B. High lipophilicity results in a significantly smaller volume of distribution

Benzodiazepines are highly protein bound and highly lipophilic. High protein binding renders a smaller free fraction of the drug available to cross the blood–brain barrier, and high lipophilicity results in a larger volume of distribution.

High lipid solubility = Large volume of distribution

70
Q

Which of the following agents DOES not cause burst suppression?

A. Etomidate

B. Isoflurane

C. Propofol

D. Midazolam

A

D. Midazolam

71
Q

Why does flumazenil have a re-sedation effect?

A. Benzodiazepine effect is eliminated more slowly than the effect of flumazenil

B. Flumazenil is long acting than benzodiazipine

A

A. Benzodiazepine effect is eliminated more slowly than the effect of flumazenil

72
Q

Which of the three benzodiazepine has the highest hepatic clearance?

A. Midazolam

B. Lorazepam

C. Diazepam

D. Remimazolam

A

A. Midazolam

Also, Lorazepam and diazepam are not soluble in water and often cause vein irritation due to the propylene glycol admixture.

Alternative formulations are available as a lipid emulsion, but with a decrease in bioavailability.

73
Q

TRUE or FALSE

Benzodiazepine has NO CEILING EFFECT.

A

FALSE

It is this enhanced affinity of the GABA-A receptor for the GABA molecule, and subsequent decreased unbinding that produces the so-called “ceiling effect.” Benzodiazepines thus have a dose dependent CNS depressant effect.

Because of the ceiling effect of benzodiazepines, an isoelectric EEG or burst suppression is not attained. This is in direct contrast to propofol and thiopental, each of which can achieve burst suppression.

Thus, the neuroprotectant effect of benzodiazepines is quite limited, but likely not entirely absent.

74
Q

Suppose you will give a pre-medication with Midazolam to a mentally challenged pediatric patient. You plan to give it via oral route. What is the recommended dose?

A. 0.5 mg/kg

B. 0.1 mg /kg

C. 0.01 mg/kg

D. 0.05 mg/kg

A

A. 0.5 mg/kg

75
Q

TRUE or FALSE

Remimazolam has a RAPID onset and follows FIRST ORDER KINETICS .

A

TRUE

It has a rapid offset that follows first-order kinetics at the
recommended doses due to metabolism by tissue esterases (similar to remifentanil), and thus does not result in accumulation of drug.

Remimazolam takes advantage of the hypnotic and amnestic effects of midazolam with a speed and mode of metabolism similar to remifentanil.

76
Q

Diazepam in comparison with Midazolam produces longer sedation primarily due to:

A. production of an active metabolites with oxidative metabolism in the liver

B. conjugation of parent drug to glucuronic acid

C. production of inactive metabolites with oxidative metabolism in the liver

A

A. production of an active metabolites with oxidative metabolism in the liver

  • Diazepam undergoes oxidative metabolism in liver and has active metabolites –> prolong its sedative effects
    Also, severe liver disease prolongs the half-life
  • Lorazepam is directly conjugated to glucuronic acid to form pharmacologic inactive metabolite
  • Midazolam undergoes oxidative metabolism in liver, but different hepatic enzymes than diazepam.

The primary metabolite is 1-hydroxymethyl midazolam - has mild CNS depressive effects

77
Q

Compared with midazolam, diazepam has which of the following characteristics:

A) greater solubility in water

B) shorter beta half-life

C) more potent ventilatory depressant effect

D) lower risk for thrombophlebitis

E) pharmacological active metabolite

A

E) pharmacological active metabolite

78
Q

Which of the following drugs is NOT directly conjugated to glucuronic acid?

A) Temazepam
B) Oxazepam
C) Lorazepam
D) Diazepam

A

D) Diazepam

79
Q

The plasma half-time of which of the following drugs is prolonged in patients with end stage cirrhotic liver disease?

A) Diazepam
B) Pancuronium
C) Alfentanil
D) all of the above

A

D) all of the above

80
Q

Which of the following statements concerning midazolam is FALSE?

A. Midazolam has greater amnestic than sedative properties

B. Its breakdown is inhibited by cimetidine

C. It produces retrograde amnesia

D. It facilitates the actions of the inhibitory neurotransmitter γ- aminobutyric acid (GABA) in the CNS

A

C. It produces retrograde amnesia

81
Q

A 78 y.o. woman with a history of reactive airway disease is taking Cimetidine 400mg at night. An additional dose is given IV 30mins before induction of anesthesia for exploratory laparotomy. Possible side effects associated with this drug include all of the following EXCEPT:

A) bradycardia
B) delayed awakening
C) confusion
D) increased metabolism of diazepam

A

D) increased metabolism of diazepam - it should decrease metabolism

Cimetidine - decreases the metabolism of benzodiazepines

82
Q

Which of the following statements regarding flumazenil is TRUE?

A) hepatic clearance is low

B) it binds irreversibly with benzodiazepine receptor binds reversibly

C) it causes hypertension and tachycardia

D) it has a shorter duration of action than midazolam

E) it reverse opioid induced respiratory depression

A

D) it has a shorter duration of action than midazolam

83
Q

Which of the drugs has the shortest elimination half-life?

A) diazepam
B) flumazenil
C) lorazepam
D) midazolam

A

B) flumazenil

FLUMAZENIL has a shorter elimination half-life than the three commonly used BENZO’s

84
Q

In which of the following ways do benzodiazepines
usually affect sleep?

(A) increased length of REM sleep
(B) decreased number of REM cycles
(C) increased Stage 0 sleep
(D) increased Stage 3 and 4 sleep
(E) increased Stage 2 sleep

A

(E) increased Stage 2 sleep

Benzodiazepines INCREASE the amount of time spent in
Stage 2 sleep.

Benzodiazepines usually decrease the amount of time spent in Stage 0, 1, 3, 4, and REM sleep. They also decrease sleep latency and usually increase the number of REM cycles.
Overall, benzodiazepines usually increase total sleep time.

When benzodiazepines are discontinued, a “rebound” in the
amount o REM sleep may occur.

85
Q

A patient is taking chronic benzodiazepines to treat
symptoms of anxiety. The patient takes an intentional
overdose of the benzodiazepine and a tricyclic antidepressant. In this situation fumazenil should be avoided due to the risk of:

(A) tachycardia
(B) seizures
(C) hearing loss
(D) malignant hypertension
(E) severe nausea

A

(B) seizures

Flumazenil should be avoided in the setting of chronic
benzodiazepine use or in cases of tricyclic antidepressant
overdose, as seizures have been reported. In general,
other side effects of fumazenil administration
include tachycardia, hypertension, hearing changes,
and nausea.

86
Q

Which of the following drugs increases cerebral blood flow while decreasing cerebral metabolic rate?

(A) Etomidate
(B) Fentanyl
(C) Isoflurane
(D) Lidocaine
(E) Midazolam

A

(C) Isoflurane

CVS effect of MIDAZOLAM:

87
Q

Cerebral blood flow is decreased by each of the following EXCEPT:

(A) etomidate
(B) midazolam
(C) nitrous oxide
(D) increased minute ventilation
(E) positive end-expiratory pressure

A

(C) nitrous oxide

Etomidate - decrease CBF
Midazolam - decrease CBF

88
Q

Which of the following statements concerning flumazenil is true?

(A) Hepatic clearance is low
(B) It binds irreversibly with the benzodiazepine receptor
(C) It causes hypertension and tachycardia
(D) It has a shorter duration of action than midazolam
(E) It reverses opioid-induced respiratory depression

A

(D) It has a shorter duration of action than midazolam

  • Hence it can cause re-sedation in the ICU when one assumes that benzodiazepine was reversed after a dose of flumazenil.
89
Q

Which of the following statements regarding the pharmacokinetics of ketamine is true?

(A) Ketamine is poorly lipid soluble

(B) The duration of action of a single induction
bolus is 2–3 minutes

(C) Ketamine has a relatively low degree of protein
binding

(D) The elimination clearance of the R- enantiomer
is larger than the S+ enantiomer

(E) clearance is independent of hepatic blood low

A

(C) Ketamine has a relatively low degree of protein
binding

90
Q

The metabolite resulting from N-demethylation of ketamine
in the liver by microsomal enzymes that still carries some degree of activity is:

(A) hydroxyketamine
(B) oxyketamine
(C) norketamine
(D) hydroxynorketamine
(E) oxynorketamine

A

(C) Norketamine

Ketamine is metabolized in the liver by N-demethylation
to form norketamine. This is then hydroxylated
to hydroxynorketamine. Both of these intermediate
metabolites are conjugated to glucuronide and excreted
in the urine.

Norketamine apparently has about 70%–80% of the activity of the original drug. Although it does not last very long providing the glucuronidation pathway is not impaired, research does suggest that it contributes somewhat to a prolongation of the effect.

91
Q

Intraoperative allergic reactions are LEAST common after patient exposure to:

A. Ketamine
B. Latex
C. Muscle relaxants
D. Hydroxyethyl starch

A

A. Ketamine

  • Ketamine and Midazolam is have least incidence of drug hypersensitivity intraoperatively.
  • Most common - NMB > Latex > Hydroxyethyl starch
92
Q

Respiratory depression is LEAST after the induction dose of which of the following drugs?

A. Etomidate
B. Ketamine
C. Fentanyl
D. Propofol

A

B. Ketamine

Induction dose of 2mg/kg can induce general anesthesia within 30 - 60 seconds.

93
Q

Which of the following cardiovascular responses would
be expected following an induction dose of ketamine?

(A) a decrease in heart rate
(B) an increase in the pulmonary capillary wedge
pressure
(C) a decrease in cardiac index
(D) an increase in right atrial pressure
(E) a decrease in left ventricular stroke work

A

(D) an increase in right atrial pressure

Ketamine is unique among intravenous anesthetics in
that it stimulates the cardiovascular system rather than
depresses it. Hemodynamic changes following an intravenous induction dose of 0.5–2 mg/kg are seen in the given table.

Interestingly, using an equia-nesthetic dose of the S+ enantiomer produces the same effect as the racemic
mixture, despite an overall dose reduction of 50%.

Moreover, the hemodynamic changes appear NO to
be dose-related; a dose of 1 mg/kg appears to produce
the same increase in blood pressure, heart rate, etc. as a
dose of 2 mg/kg or 0.5 mg/kg.

Ketamine appears to act centrally by stimulating the sympathetic system, rather than by a peripheral mechanism such as inhibition of the baroreceptor reflex.

94
Q

Which of the following factors increases the risk or
emergence reactions related to ketamine anesthesia?

(A) playing music during anesthesia
(B) age under 18 years
(C) low dose of ketamine
(D) female sex
(E) pretreatment with benzodiazepines

A

(D) Female sex

Several factors have been shown to increase the
incidence of emergence reactions. These include
female sex, adult (vs. pediatric) patients, and large
and/or rapidly administered doses of ketamine.

Patients who dream frequently at home may also be
at higher risk or vivid dreaming after ketamine anesthesia.
Playing music during anesthesia has been postulated
by some to increase the incidence due to a possible pro-hallucinatory effect, but this has been disproven.

Benzodiazepines (including midazolam, lorazepam,
and diazepam) are very effective at reducing the incidence
o emergence reactions following ketamine.

Ref: Miller RD. Miller’s Anesthesia. 8th ed

95
Q

During acute pericardial tamponade, which of the following
best describes the physiologic rationale or the use of ketamine as an induction agent?

(A) a reduction in left ventricular stroke volume
(B) a decrease in pulmonary vascular resistance
(C) a reduction in systemic vascular resistance
(D) an increase in right atrial pressure
(E) an increase in contractility

A

D. an increase in right atrial pressure

During acute pericardial tamponade, the key problem
is restriction of cardiac chamber size during diastole
due to the expansion of the pericardial sac. This is
especially true of the more compliant, thin-walled
right heart. This restriction limits the right-sided
stroke volume, which effectively lowers overall cardiac
output. The goals of anesthetic management during
tamponade are to maintain the preload as much as
possible, and to promote the ejection of whatever
stroke volume is in the ventricles. This gives rise to the
phrase “ fast, full, and forward”—a rapid heart rate
and full preload will give the cardiac output a fighting
chance until the pressure can be relieved. Bradycardia
and a low CVP are not well tolerated in these
circumstances

Miller | 8th edit

96
Q

Ketamine is a racemic mixture of S and R enantiomers. Which of the following is ACCURATELY described?

A. The R(+) enantiomer more potent than the S(+) enantiomer

B. The S enantiomer has a longer duration

C. The S enantiomer is cleared more rapidly

D. Ketamine has a very high lipophilicity and high protein binding

A

C. The S enantiomer is cleared more rapidly

  • The induction dose of ketamine is 0.5 to 2 mg/kg for intravenous administration and 4 to 6 mg/kg for IM
    administration.

Barash | 9th edit

97
Q

The elimination of Ketamine is primarily thru:

A. Kidney

B. Liver

C. Bile

D. Plasma esterases

A

B. Liver

The liver extensively metabolizes ketamine by demethylation to its principle metabolite norketamine.

Norketamine is biologically active but only has 20% to 30%
the activity of racemic ketamine. Norketamine is eliminated by renal excretion.

  • Due to its lipophilicity, ketamine is only partially removed by dialysis.
98
Q

Postanesthetic shivering can be treated with all of the following EXCEPT

A. Naloxone
B. Physostigmine
C. Magnesium sulfate
D. Dexmedetomidine

A

A. Naloxone

Medications that can be used for post-anesthetic shivering:

Clonidine
Dexmedetomidine
Ketanserin( Anti-serotonigenic)
Magnesium SO4
Meperidine
Tramadol
Physostigmine

  • NALOXONE do not have a role in the post-anesthetic shivering
99
Q

TRUE of Remimazolam:

A. Is less potent than its main metabolite

B. Is suitable for patients with liver disease

C. Is metabolized rapidly by amine precursor uptake and
decarboxylation (APUD) cells in the gastrointestinal (GI) tract

D. Is a commercially available mixture of remifentanil plus
midazolam

A

B. Is suitable for patients with liver disease

100
Q

One of the indications of Ketamine is major depression. What is the IV sub-anesthetic dose of Ketamine for treatment of depression?

A. 0.1 mg/kg

B. 0.01 mg/kg

C. 0.5 mg/kg

D. 0.05 mg/kg

A

C. 0.5 mg/kg

The duration of ketamine’s antidepressant effect may last from a couple of days to approximately 2 weeks following a single injection.

For treatment of depression, ketamine is typically infused intravenously over 40 minutes at a subanesthetic dose of 0.5
mg/kg.

  • Ketamine has a rapid effect on depression with decreased depression symptoms and suicidal ideation within 1 hour of administration
101
Q

TRUE or FALSE

Ketamine is not safe for increased ICP, therefore not recommended for patients with seizure disorder.

A

FALSE!

The excitatory CNS effects of ketamine would increase CMRO2 and increase CBF. However, studies have found that ICP typically remains normal with ketamine administration in neurosurgical patients with controlled ventilation. In fact, ketamine may be neuroprotective.

Ketamine is associated with epileptiform activity on EEG;
however, these excitement waveforms are not seen in the cortex, and therefore ketamine seems unlikely to precipitate a seizure.

BASIC EXAM Part I | Question Bank (30 decks)

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