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ADVANCED PHARMACOLOGY I > CH 4 Inhaled Anesthetics PHARMACOKINETICS ONLY > Flashcards

CH 4 Inhaled Anesthetics PHARMACOKINETICS ONLY Flashcards

KEY POINTS FROM STOELTINGS AND LECTURE

1
Q

The rate of increase of the PA toward the PI is _______ related to the solubility of the anesthetic in blood

A

The rate of increase of the PA toward the PI (maintained constant by mechanical ventilation of the lungs) is inversely related to the solubility of the anesthetic in blood.

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2
Q

What is described by Blood:Gas partition coefficient ?

A

the solubility of an inhaled anesthetic in the blood

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3
Q

What happens with the inhaled anesthetics when the blood:gas partition coefficient is high?

A

When the blood:gas partition coefficient is high, a large amount of anesthetic must be dissolved in the blood before the Pa equilibrates with the PA.

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4
Q

What is the overpressure technique?

A

Increasing the PI above the required maintenance for anesthesia

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5
Q

What technique is used to speed the induction of anesthesia? How is this achieved?

A

The overpressure technique

Achieved by Increasing the PI above the required maintenance for anesthesia

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6
Q

Sustaining a delivery of HIGH PI will result in

A

Anesthetic overdose

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7
Q

The overpressure technique can result in

A

Anesthetic overdose

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8
Q

True or False: Blood can be considered a pharmacologically inactive reservoir, the size of which is determined by the solubility of the anesthetic in blood.

A

True

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9
Q

What happens when the blood solubility is low?

A

Minimal amounts of inhaled anesthetic must be dissolved before equilibration is achieved; therefore, the rate of increase of PA and Pa, and thus onset-of-drug effects such as the induction of anesthesia, are rapid.

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10
Q

The inhalation of a constant PI of nitrous oxide, desflurane, or sevoflurane for about 10 minutes results in a PA that is ________ of the PI

A

≥80%

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11
Q

Why the overpressure technique is more readily accepted with sevoflurane than desflurane?

A

Because sevoflurane is less pungent than desflurane

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12
Q

How does a decreased solubility of volatile anesthetic would manifest in anemic patient?

A

Increased rate of increase in PA
Therefore a more rapid induction of anesthesia

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13
Q

How does fatty meals ingestion affect the solubility of inhaled anesthetics?

A

Ingesting fatty meals alters blood composition, resulting in ~ 20% increase in the solubility of volatile anesthetics

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14
Q

Blood:gas partition coefficients are altered by

A
  • individual variations in water
    -lipid and protein content
  • the hematocrit of whole blood.
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15
Q

blood:gas partition coefficients are about _____ less in blood with a hematocrit of 21% compared with blood with a hematocrit of 43%

A

20%

Decreased solubility reflects the decrease in lipid-dissolving sites normally provided by erythrocytes.

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16
Q

Solubility varies with

A

age

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17
Q

Which inhaled anesthetics solubility is about 18% less in neonates than in the elderly compared with young adults?

A

halothane, enflurane, methoxyflurane, and isoflurane

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18
Q

Which inhaled anesthetics solubility is not different in neonates and adults?

A

Sevoflurane and desflurane

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19
Q

Tissue:Blood partition coefficient

A

Determine the anesthetic uptake into tissues and the TIME necessary for equilibration of tissues with the Pa.

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20
Q

How the time of equilibration in tissue: blood coefficient is estimated?

A

By calculating a time constant (amount of inhaled anesthetic that can be dissolved in the tissue divided by tissue blood flow) for each tissue.

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21
Q

One time constant on an exponential curve represents

A

63% equilibration

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22
Q

Three-time constants on an exponential curve are equivalent to

A

95% equilibration

Three-time constants 5- 15 minutes

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23
Q

For volatile anesthetics, equilibration between the Pa and PBRAIN depends on

A

the anesthetic’s blood solubility and requires 5 to 15 minutes (three time constants)

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24
Q

What happens with the inhaled anesthetics when there is fat and low blood flow to the tissues?

A

Prolongation of tissue: blood coefficient

Prolongs the time required to narrow anesthetic partial pressure differences between arterial blood and fat.

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25
Q

Fasting before elective operations results in transport of fat to the liver, which could increase

A

Anesthetic uptake by this organ and modestly slow the rate of increase in a volatile anesthetic’s PA during anesthesia induction.

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26
Q

Oil:Gas partition coefficient and MAC estimation

A

Estimated MAC can be calculated as 150 divided by the oil: gas partition coefficient

The constant, 150, is the average value of the product of oil:gas solubility

Using this constant, the calculated MAC for a theoretical anesthetic with an oil: gas partition coefficient of 100 would be 1.5%

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27
Q

What is the blood:gas of N2O?

A

0.46

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28
Q

N20 is about _______ times greater (solubility) than of nitrogen (0.014)

A

34 times

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29
Q

What are the effects of N2 on a compliant wall gas cavity?

A

Expansion

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30
Q

What are the effects of N2 on a non-compliant wall gas cavity?

A

pressure build-up

increase intracavitary pressure

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31
Q
A
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32
Q

compliant wall gas cavity examples

A

intestines
pneumothorax
pulmonary blebs
air bubbles

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33
Q

non- compliant wall gas cavity examples

A

middle ear
cerebral ventricles
supratentorial space

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34
Q

N2O magnitude of VOLUME or Pressure increase is influenced by

A

Partial pressure of N2O
Blood flow to air-filled cavity
Duration of N2O administration

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35
Q

N2O transfer to closed gas spaces can cause

A

-Rapid expansion of a pneumothorax

-Increased bowel gas

  • Tympanic membrane rupture
    this will cause otitis and pot op N/V

-Increased intraocular gas after gas bubble placement
this can result in compression of the retinal artery=visual loss

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36
Q

How does cardiopulmonary bypass produce changes in blood:gas solubility?

A

Cardiopulmonary bypass produces changes in blood: gas solubility depending on the temperature and the priming solution.

Volatile anesthetics initiated during cardiopulmonary bypass take longer to equilibrate, where as the drugs already present are diluted; potentially decreasing the depth of anesthesia

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37
Q

INCREASED Cardiac Output and inhaled anesthetic uptake

A

-Increased CO, increases uptake

-Rate of increase of PA and induction are SLOWER

Increased CO results in more rapid UPTAKE

The rate of increase in the PA and anesthesia induction are SLOWED

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38
Q

DECREASED Cardiac Output and inhaled anesthetic uptake

A

-Decreased CO, decreased uptake

-Rate of increase of PA and induction are FASTER

Decreased CO speeds the rate of increase of the PA because there is less uptake to oppose input

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39
Q

Changes in cardiac output most influence the rate of increase of the PA of a_________anesthetic.

A

Soluble

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40
Q

The rate of increase of the PA of a __________ anesthetic, such as nitrous oxide, is rapid regardless of physiologic deviations of the cardiac output around its normal value.

A

poorly soluble

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41
Q

Doubling the cardiac output will _________ the uptake of soluble anesthetic from alveoli, slowing the rate of increase of the PA.

A

increase

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42
Q

decreases in cardiac output due to an excessive dose of volatile anesthetic results in an _________ in the PA, which further _________ anesthetic depth and thus cardiac depression.

A

decreases in cardiac output due to an excessive dose of volatile anesthetic results in an increase in the PA, which further increases anesthetic depth and thus cardiac depression.

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43
Q

Distribution of cardiac output will influence the

A

rate of increase of the PA of an anesthetic

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44
Q

infants have a ________ perfusion of vessel-rich group tissues than do adults and, consequently, show a ___________ rate of increase of the PA toward the PI

A

infants have a relatively greater perfusion of vessel-rich group tissues than do adults and, consequently, show a faster rate of increase of the PA toward the PI

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45
Q

How does the presence of a Right-to-Left shunt affect Pa?

A

The R-L shunt has dilutive effects and this result in a decreases Pa and a slower induction

When a right-to-left shunt is present, the DILUTING effect of the shunted blood on the partial pressure of anesthetic in blood coming from ventilated alveoli results in a decrease in the Pa and a slowing in the induction of anesthesia.

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46
Q

Which category of inhaled anesthetics will have a more pronounced impact in the presence of a R-L shunt?

A

The impact of a R-L shunt is more pronounced with less SOLUBLE inhaled anesthetic than with more soluble

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47
Q

Left-to-right tissue shunts occurs with

A

arteriovenous fistulas, volatile anesthetic-induced increases in cutaneous blood flow

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48
Q

Left-to-right tissue shunts will result in

A

in the delivery of blood to the lungs with a higher partial pressure

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49
Q

TRUE or FALSE left-to-right shunts offset the dilutional effects of a right-to-left shunt on the Pa.

A

TRUE

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50
Q
A
51
Q

Tissue uptake affects uptake at the __________by controlling the rate of increase of the mixed venous partial pressure of anesthetic.

A

Tissue uptake affects uptake at the lung by controlling the rate of increase of the mixed venous partial pressure of anesthetic

52
Q

Factors that determine tissue uptake

A

tissue solubility, tissue blood flow, and arterial-to-tissue partial pressure differences

53
Q

Highly perfused tissues (brain, heart, kidneys) in the adult account for ______ % of body mass but receive ______ % of the cardiac output

A

<10%

75%

54
Q

Which group tissue equilibrates rapidly with the Pa?

A

The vessel rich group tissues

55
Q

Skeletal muscles and fat represent about______% of the body mass but receive only about _____% of the cardiac output

A

70%

25%

56
Q

What does a continued uptake after saturation of VRG reflects?

A

entrance into skeletal muscle and fat this is a slow process

57
Q

What does a continued uptake from the VRG result in?

A

In a continued Av-D difference for several hours

58
Q

The time for equilibration of vessel-rich group tissues is more rapid for
__________ and ________than for ___________

A

The time for equilibration of vessel-rich group tissues is more rapid for neonates and infants than for adults

This difference reflects the greater cardiac output to vessel-rich group tissues in the very young as well as decreased solubility of anesthetics in the tissues of neonates. Furthermore, skeletal muscle bulk comprises a small fraction of body weight in neonates and infants.

59
Q

VRG receives _____ of CO and accounts for _______ of body mass

A

75%
10%

60
Q

Muscle group receives _____ of CO and accounts for _______ of body mass

A

19%

50%

61
Q

Fat group receives _____ of CO and accounts for _______ of body mass

A

6%

20%

62
Q

Vessel Poor group receives _____ of CO and accounts for _______ of body mass

A

<1%

20%

63
Q

The recovery of anesthesia is depicted (show) by

A

The rate of decrease in the PBRAIN as reflected by the PA

64
Q

P Brain represents

A

the partial pressure of the anesthetic in the brain, which is closely related to the depth of anesthesia

65
Q

The concentration of the inhaled anesthetic in tissues depends highly on

A

The solubility of the inhaled drug and the duration of its administration.

66
Q

Continued tissue uptake of anesthetic will depend on

A

The solubility of the inhaled anesthetic and the duration of anesthesia, with the impact being most important with soluble anesthetics

67
Q

For which category of inhaled anesthetic the time to recovery is prolonged in proportion to the duration of anesthesia ?

A

For the soluble anesthetics Halothane and Isoflurane

68
Q

With which category of inhaled anesthetics the impact of duration of administration on time to recovery is minimal?

A

With poorly soluble anesthetics Sevoflurane and Desflurane

69
Q

TRUE or FALSE: There is a concentration effect during the recovery of anesthesia such as it occurs with induction

A

False, there is no concentration effect such as the one occurring during induction of anesthesia because it is not possible to administer less than zero

70
Q

The rate of decrease of the PA during recovery from anesthesia will be _______ than the rate of increase of the PA during induction of anesthesia.

A

faster, more rapid

71
Q

The patient’s exhaled gases containing anesthetic will be rebreathed unless fresh gas flow rates are _________ (at least ________L per minute of oxygen) after anesthesia.

A

Increased

5L per minute of oxygen

72
Q

The pharmacokinetics of the elimination of inhaled anesthetics depends on

A

The length of administration and the blood-gas solubility of the inhaled anesthetic.

73
Q

When comparing inhaled anesthetics recovery; the recovery is always the fastest for:

A

Desflurane, the most insoluble anesthestetic

73
Q

The most insoluble anesthetic is

A

Desflurane

74
Q

When comparing inhaled anesthetics recovery; the recovery is always the slowest for:

A

Isoflurane, the most soluble anesthetic

75
Q

The most soluble anesthetic is

A

Isoflurane

76
Q

When does Diffusion Hypoxia occur?

A

When inhalation of N2O is ABRUPTLY DISCONTINUED.

This will lead to a reversal of partial pressure gradients such as N2O leaves the blood to enter the alveoli

77
Q

Initially during diffusion hypoxia the high-volume outpouring from N2O from blood to alveoli will dilute the

A

PA02

78
Q

Dilution of the ______ can decrease inspiratory drive

A

PACO2

79
Q

Diffusion hypoxia will cause dilution of

A
  1. PAO2 (the first one to be diluted)
  2. PACO2
80
Q

The outpouring effect of nitrous oxide into the alveoli is greatest during the first ____ to ______ minutes after discontinuation at the conclusion of anesthesia

A

the first 1 to 5 minutes

81
Q

What is done in order to prevent diffusion hypoxia from causing arterial hypoxemia at the end of the case?

A

Immediately giving 100% oxygen to alleviate dilutive effects (on PAO2) of N2O

82
Q

What is done to alleviate dilutive effects of N2O?

A

Immediately giving 100% oxygen

83
Q

Define Minimal Alveolar Concentration (MAC)

A

The concentration at 1 atm that prevents skeletal muscle movement in response to a supramaximal painful stimulus (surgical skin incision) in 50% of patients

The MAC allows a quantitative analysis of the effect, if any, of various physiologic and pharmacologic factors on anesthetic requirements

84
Q

One MAC is the _________ dose

A

50% effective dose

85
Q

Immobility produced by inhaled anesthetics is measured by

A

MAC

86
Q

MAC is mediated principally by effects of inhaled anesthetics on

A

spinal cord

87
Q

True or False: with inhaled anesthetics Only a minor component of immobility results from cerebral effects

A

true

88
Q

TRUE or FALSE Decerebration change MAC

A

False, decerebration does not change MAC

89
Q

MAC establishes

A

A common measure of potency (partial pressure at steady state) for inhaled anesthetics.

90
Q

What is an unique feature of MAC?

A

Its consistency varies only 10% to 15% among individuals.

91
Q

MAC awake

A

The concentration of anesthetic that prevents CONSCIOUSNESS in 50% of persons, is reliably about half of MAC

92
Q

MAC-memory

A

The concentration of anesthetic that is associated with AMNESIA in 50% of patients.

Significantly less than MAC-awake.

93
Q

Inhalation anesthetic requirements are affected by

A

age and body temperature

94
Q

Age and MAC: Increasing age results in

A

a progressive decrease in MAC of about 6% per decade

95
Q

MAC is decreased nearly _____% during pregnancy and in the early postpartum period

A

30%

Although MAC is reduced in parturients, there is evidence that the concentration-response in the brain is not changed. The dose of volatile anesthetic required to induce the electroencephalogram (EEG) changes expected with hypnosis are not changed in pregnancy

96
Q

After postpartum period=, the MAC return to normal values in ___ to ___ hours

A

12 to 72 hours

97
Q

Factors that increase MAC

A
98
Q

Factors that decrease MAC

A
99
Q

Factors that do not change/alter MAC

A
100
Q

MAC is increased in women with natural red hair; this is due to

A

due to mutation of the melanocortin-1 receptor gene and increased pheomelanin concentrations

101
Q

Which inhaled anesthetic MAC is affected by the use of cyclosporine? How it’s affected?

A

Isoflurane

Increases MAC

102
Q

TRUE OR FALSE The MAC values may vary with the type of stimulus; tetanic stimulation and trapezius squeeze are considered noninvasive stimulation patterns that are relatively equivalent to surgical skin incision, although in contrast to skin incision, these events can be repeated.

A

TRUE

103
Q

TRUE OR FALSE Tracheal intubation requires the highest MAC to prevent skeletal muscle responses and may represent a true supramaximal stimulation

A

TRUE

104
Q

TRUE OR FALSE

The MAC values for inhaled anesthetics are additive.

For example, 0.5 MAC of nitrous oxide plus 0.5 MAC isoflurane has the same effect at the brain as does a 1 MAC of either anesthetic alone

A

TRUE

105
Q

1 MAC dose prevents ________________ in response to a painful stimulus in 50% of patients, whereas a modest increase to about 1.3 MAC prevents __________________ in at least 95% of patients.

A

1 MAC dose prevents skeletal muscle movement in response to a painful stimulus in 50% of patients, whereas a modest increase to about 1.3 MAC prevents movement in at least 95% of patients.

106
Q

What is the Meyer Overton Theory?

A

Known as the critical volume hypothesis.

Proposes that there is a correlation between lipid solubility (oil:gas) and potency

suggest that inhaled anesthetics acts on the lipid portion of nerve membranes

107
Q

Steresoselectivity suggest that

A

inhaled anesthestics bind to specific channel proteins and not to the lipid layers

108
Q

Isoflurane has been shown to act stereoselectively on neuronal channels, with the levoisomer being _______ potent than the dextroisomer

A

more

109
Q

Ionotropic receptors are composed of

A

Several subunits.
γ-aminobutyric acid receptor type A (GABAA) and nicotinic acetylcholine receptors

110
Q

What are metabotropic receptors?

A

monomeric receptors consisting of seven transmembrane segments

G proteins act as second messengers to activate other signaling molecules such as protein kinases or potassium or calcium channels

111
Q

Which are the major mediators of inhibitory neurotransmission in the spinal cord and may mediate part of the immobility produced by inhaled anesthetics

A

Glycine receptors

112
Q

GABA A and mediation of anesthetic action:

A

GABA A receptors do not mediate immobility produced by inhaled anesthetics.

GABAA receptors are potentiated at MACs of all clinically used volatile anesthetics, but their enhancement of GABAA receptor activation minimally influences MAC

113
Q

Which is the principal excitatory neurotransmitter in the CNS?

A

Glutamate

114
Q

Glutamate receptors include

A

NMDA, AMPA and KAINATE

115
Q

Two-pore potassium channels are

A

intrinsic membrane receptor/ion channels that normally act to maintain the cell’s resting potential and responds to internal stimuli such as a change in pH

116
Q

The TASK-3 receptors are

A

Anesthetic-sensitive receptors play a role in maintaining theta oscillations in the EEG associated with anesthesia and the duration of natural deep sleep.

Anesthetic interaction with TASK channels may contribute to anesthetic-induced neuroprotective effects in ischemia-reperfusion injury.

117
Q

Sodium channels that ___________ the release of neurotransmitters may be more sensitive to anesthetics

A

modulate

118
Q

Intravenous administration of lidocaine, which is a nonspecific sodium channel blocker,
_______________ MAC.

A

decreases

119
Q

Hyperpolarization-activated cyclic nucleotide–gated channels

A

Are voltage-gated ion channels that are expressed throughout the body.

It is particularly important in regulating rhythmogenicity in heart and brain.

120
Q

Inhaled anesthetics depress

A

inhaled anesthetics depress excitatory AMPA and NMDA receptor–mediated currents by actions independent of inhibitory GABAA and glycine receptor–mediated currents.

121
Q

Why volatile anesthetics have been called total anesthetics?

A

Volatile anesthetics have been called total anesthetics because they can be used as a single agent to provide general anesthesia.

122
Q

General Anesthesia

A

unconsciousness of the brain plus immobility in response to noxious stimuli

ADVANCED PHARMACOLOGY I (2 decks)

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