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APEX Pharmacology > PHARMACOLOGY-Inhaled anesthetics PK > Flashcards

PHARMACOLOGY-Inhaled anesthetics PK Flashcards

1
Q

What are the 3 categorizations of inhaled anesthetics

A

Ethers
Alkanes
Gases

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2
Q

What form do ethers and alkanes take at atmospheric pressure and room temperature

A

Liquids

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3
Q

What form do nitrous oxide and xenon take at atmospheric pressure and room temperature

A

Gas

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4
Q

How are the halogenated anesthetics differentiated from each other

A

By the number of fluorine atoms

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5
Q 
How many fluorine atoms does each anesthetic have
Halothane
Isoflurane
Desflurane
Sevoflurane
A 
Halothane= 3
Isoflurane= 5
Desflurane= 6
Sevoflurane= 7
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6
Q

Which halogenated anesthetics have 3, 5, 6, 7 fluorine atoms

A 
3= halothane
5= isoflurane 
6= desflurane
7= sevoflurane
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7
Q

What molecule is added to isoflurane that makes it more potent

A

Chlorine atom

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8
Q

Describe the difference between isoflurane and desflurane.

How does this difference affect PK/PD

A

Iso has a chlorine atom replacing 1 fluorine atom.

This extra fluorine reduces des potency and metabolism while increasing vapor pressure

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9
Q

Compare the potency of sevoflurane and desflurane

A

Sevo > des

x3 potency

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10
Q

What effect does full fluorination of desflurane have potency, vapor pressure and biotransformation

A

Potency = DECREASED, requiring increased MAC
-decreased oil:gas solubility

Vapor pressure = INCREASED d/t decreased intermolecular attraction requiring heated vaporizer

Biotransformation= INCREASED resistance decreasing metabolism

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11
Q

Rate the potency of sevoflurane, desflurane, and isoflurane from greatest to least

A

Isoflurane&raquo_space;Sevoflurane&raquo_space;> desflurane

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12
Q

What effect does the chlorine atom in isoflurane have on solubility and potency

A

Increases potency

Increases blood and tissue solubility

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13
Q

What molecules and chemical alterations make halothane different from the ether anesthetics

A

Lacks an ether bridge (C-O-C)

Presence of Cl and Br

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14
Q

Define vapor pressure

A

The pressure exerted by a vapor in equilibrium with its liquid or solid phase inside of a closed container

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15
Q

How does vapor pressure relate to temperature

A

Directly proportional

Increased temp = increased VP

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16
Q

Define boiling point

A

The temperature where matter transitions from a liquid to gaseous state

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17
Q

How does boiling point relate to pressure and tempurature

A

Boiling occurs when VP equals atmospheric pressure

At high altitudes, liquids boil at lower temperatures as a function of reduced atm pressure

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18
Q

Define partial pressure

A

The fractional amount of pressure that a single gas exerts within a gas mixture

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19
Q

What is Dalton’s gas law

A

Law of partial pressures
Total gas pressure in a container is equal to the sum of the partial pressure exerted by each gas

P total = P1 + P2 + P3…

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20
Q

Define evaporation

A

The process where compounds transition from liquid to gaseous stat at a temperature below boiling point

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21
Q

When does boiling occur

A

When vapor pressure equals atm pressure
Open container is required
Increased atm P = increased boiling point
Decreased atm P = decrease boiling point

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22
Q

What effect does pressure have on boiling point

A

Increased pressure = increased BP

Decreased pressure = decreased BP

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23
Q

What determines the depth of anesthesia with gases

A

The partial pressure of the anesthetic agent in the brain NOT the volume precent

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24
Q

What can transform volatile anesthetics into toxic compounds (2)

A

Carbon dioxide absorbent

Liver

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25
Q

What does stability refer to with anesthetic gases

A

The ability to resist breakdown or metabolism

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26
Q

What can desflurane and isoflurane produce in desiccated soda lime

A

Carbon monoxide

des>iso

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27
Q

What does sevoflurane produce when unstable

A

compound A

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28
Q 
Vapor Pressure
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 157 mmHg
Des= 669 mmHg
Iso= 238 mmHg
N2O= 38,770 mmHg
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29
Q 
Boiling Point
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 59*C
Des= 22*C
Iso= 49*C
N2O= -88*C
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30
Q 
Molecular weight
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 200 g
Des= 168 g
Iso= 184 g
N2O= 44 g
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31
Q 
Stable in hydrated CO2 absorber (Y/N)
Sevo=
Des=
Iso=
N2O=
A 
Sevo= N
Des= Y
Iso= Y
N2O= Y
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32
Q 
Stable in dehydrated CO2 absorber (Y/N)
Sevo=
Des=
Iso=
N2O=
A 
Sevo= N
Des= N
Iso= N
N2O= Y
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33
Q 
Toxic by-product
Sevo=
Des=
Iso=
N2O=
A 
Sevo= compound A
Des= carbon monoxide
Iso= carbon monoxide
N2O= none
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34
Q

Define solubility of inhalation anesthetics

A

The ability of the anesthetic agent to dissolve into blood and tissue

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35
Q

What does the blood:gas partition coefficient describe

A

The relative solubility of an inhalation anesthetic in blood vs. in the alveolar gas when the partial pressures between the two compartments are equal

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36
Q 
Blood:gas coefficients for
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 0.65
Des= 0.42
Iso= 1.46
N2O= 0.46
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37
Q

What does the partition coefficient measure

A

solubility

The relative solubility of a solute in 2 different solvents (blood vs alveolar gas)

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38
Q

What is the likelihood of anesthetic uptake in the blood with a low blood:gas solubility

A

Less likely to be taken up into the blood (less blood soluble)

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39
Q

What is the distribution of anesthetic agent with low blood:gas solubility (blood, alveolus, brain)

A

More agent is available to exert partial pressure in alveoli and brain

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40
Q

What is the likelihood of anesthetic uptake in the blood with a high blood:gas solubility

A

More likely to be taken up in the blood (more blood soluble)

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41
Q

What is the distribution of anesthetic agent with high blood:gas solubility (blood, alveolus, brain)

A

Less agent is available to exert a partial pressure in the alveoli and brain

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42
Q 
Blood:Gas partition coefficient
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 0.65
Des= 0.42
Iso= 1.46
N2O= 0.46

Iso > Sevo > N2O >Des

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43
Q 
Brain:Blood partition coefficient
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 1.7
Des= 1.3
Iso= 1.6
N2O= 1.1

Sevo > Iso > Des > N2O

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44
Q 
Muscle:Blood partition coefficient
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 3.1
Des= 2.0
Iso= 2.9
N2O= 1.2

Sevo > Iso > Des > N2O

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45
Q 
Fat:blood partition coefficient
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 47.5
Des= 27.2
Iso= 44.9
N2O= 2.3

Sevo > Iso > Des > N2O

46
Q 
Oil:gas partition coefficient
Sevo=
Des=
Iso=
N2O=
A 
Sevo= 47
Des= 19
Iso= 91
N2O= 1.4

Iso > Sevo > Des > N2O

47
Q

Equation for partition coefficient

A

partition coefficient = ([anesthetic dissolved in BLOOD]/[anesthetic inside ALVEOLUS])

48
Q

How is an anesthetic state induced with volatile anesthetics

A

Building up a partial pressure of anesthetic agent in the brain and spinal cord

49
Q

How de the alveolar and brain concentrations of anesthetic agents correlate

A

Agent in the alveoli is proportional to its concentration inside the brain

50
Q

What measurable anesthetic value is a surrogate for anesthetic partial pressure in the brain

A

Alveolar partial pressure (FA)

51
Q

What determines the amount of anesthetic agent inside the alveoli

A

The balance between input (vaporizer setting) and uptake in blood

52
Q

What 3 factors determine anesthetic uptake in the blood

A
  1. Agent solubility
  2. Partial pressure difference between alveoli and blood
  3. Cardiac output
53
Q

How does an anesthetics solubility affect FA/FI equilibration

A

Low solubility = decreased blood uptake = increase rise of concentration = faster equilibration of FA/FI = faster onset

High solubility = increased blood uptake = slower rise in concentration = slower equilibration of FA/FI = slower onset

54
Q

How does alveolar concentration of an anesthetic correlate to blood and brain concentrations

A

Alveolar concentration is proportional to the concentration in blood which is proportional to concentration in the the brain

55
Q

What is FI in relation to the FA/FI curve

A

Inhaled fraction of anesthetic

56
Q

What does the FA/FI curve describe

A

the speed at which alveolar partial pressure equilibrates with partial pressure leaving the vaporizer

57
Q

What does a decreased rate of rise of FA/FI mean for induction

A

slower induction

58
Q

How is the rate of rise of the FA/FI curve decreased

A

Increased CO
Increased FRC
Decreased FGF

59
Q

What does an increased rate of rise of FA/FI mean for induction

A

faster induction

60
Q

How is the rate of rise of the FA/FI curve increased

A

Decreased time constant
Decreased anatomic dead space
Increased alveolar ventilation

61
Q

What are 5 factors that influence the rate of anesthetic delivery to the alveoli

A
  1. Setting on the vaporizer
  2. Time constant of the delivery system
  3. Anatomic dead space
  4. Alveolar ventilation
  5. Functional residual capacity
62
Q

What 3 factors influence removal of anesthetic from the alveoli

A
  1. Agent solubility
  2. Partial pressure difference between the alveoli and blood
  3. Cardiac output
63
Q

How do anesthetic wash in or uptake increase or decrease FA/FI

A

Greater wash-in and reduced uptake increase FA/FI

Reduced wash-in or increased uptake decrease FA/FI

64
Q

Which direction does the FA/FI curve move when onset is faster

A

Curve is pushed up because of increased FA/FI

65
Q

What 5 factors increase anesthetic wash-in

How does this affect anesthetic onset and FA/FI curve

A
  1. High FGF
  2. High alveolar ventilation
  3. Low FRC
  4. Low time constant
  5. Low anatomic dead space

Faster onset and increased FA/FI

66
Q

What 3 factors decrease anesthetic uptake

How does this affect anesthetic onset and FA/FI curve

A
  1. Low solubility
  2. Low CO
  3. Low Pa-Pv difference

Faster onset and increased FA/FI

67
Q

What 5 factors decrease anesthetic wash-in

How does this affect anesthetic onset and FA/FI curve

A
  1. Low FGF
  2. Low alveolar ventilation
  3. High FRC
  4. High time constant
  5. High anatomic dead space

Slower onset and decreased FA/FI

68
Q

What 3 factors increase anesthetic uptake

How does this affect anesthetic onset and FA/FI curve

A
  1. High solubility
  2. High CO
  3. high Pa-Pv difference

Slower onset and decrease FA/FI

69
Q

What percentage of body weight is accounted for by vessel rich group
How much CO does it receive

70
Q

What 4 tissue groups are considered for distribution of anesthetic

A

VRG
Muscle group
Fat group
Vessel poor group

71
Q

What 3 factors is tissue uptake dependent on

A
  1. Tissue blood flow
  2. Solubility of the anesthetic in the tissue
  3. Arterial blood:tissue partial pressure gradient
72
Q

What 5 organs make up the vessel rich group

A 
Heart
Brain
Kidneys
Liver
Endocrine glands
73
Q

What percentage of body mass is the muscle/skin group

How much CO does it receive

A

50% of mass

20% of CO

74
Q

What percentage of body mass is the fat group

How much CO does it receive

A

20% of mass

5% of CO

75
Q

What percentage of body mass is the vessel poor group

How much CO does it receive

A

20% of mass

<1% CO

76
Q

Which tissue group is first to equilibrate with FA and why

A

The VRG

because it receives 75% of CO

77
Q

After the VRG is fully saturated which group is responsible for the majority of continued tissue uptake

A

Muscle group

78
Q

Why is the muscle group slower to saturate than the VRG

A

larger mass/capacity and lower CO

79
Q

Why is the fat group capable of storing large amounts of anesthetic agent

A

Because halogenated agent

80
Q

How does N2O into tissue groups differ from halogenated anesthetics

A

It partitions nearly the same into all compartments

It quickly diffuses into the GAS containing areas of the body, such as the GI tract and middle ear

81
Q

What 3 ways are inhaled anesthetics eliminated from the body

A
  1. Elimination from the alveoli (primary)
  2. Hepatic biotransformation (secondary)
  3. Percutaneous loss (minimal)
82
Q

What percentage of each halogenated anesthetic is transformed by the liver

A 
Halothane= 20%
Sevo= 2%
Iso= 0.2%
Des= 0.02%
N2O= 0.004%

Halo > Sevo > Iso > Des > N2O

83
Q

Compare the hepatic metabolism of the inhaled anesthetics from greatest to least

A

Halo > Sevo > Iso > Des > N2O

DISH (from lowest to highest)

84
Q

What metabolic by-product is a result of des and iso metabolism

A

Trifluoroacetic acid

85
Q

What metabolic by-product is a result of sevo metabolism

A

Free fluoride ions

86
Q

How are halogenated anesthetics metabolized in the liver

A

By the P450 system carried out by CYP2E1

87
Q

What inhaled anesthetic by-product can precipitate immune-mediated hepatic dysfunction

A

Trifluoroacetic acid

by-product of halothane metabolism

88
Q

What anesthetic by-products are produced inside the body vs outside the body (soda lime)

A

Inside = free fluoride ions, TFA

Outside = compound A, carbon monoxide

89
Q

How can compound A buildup in circuits be prevented

A

Minimum FGF of 1 L/min for up to 2 MAC-hrs

2 L/min after 2 MAC-hrs

90
Q

What is a MAC-hr

A

1 x MAC that prevents movement in response to noxious stimuli in 50% of subjects given 1 MAC-hr

91
Q

Why is the rate of rise for N2O FA/FI curve faster than des

A

The concentrating effect

92
Q

What 4 factors alter the speed of anesthetic induction and emergence

A

Concentration effect
Concentrating effect
Augmented gas inflow effect
Ventilation effect

93
Q

Describe concentration effect

A

The higher the concentration of inhalation anesthetic delivered to the alveolus, the faster its onset

aka overpressuring

Most prominent with N2O and higher soluble agents

94
Q

What two components rate to the concentration effect

A

ConcentratING effect

Augmented gas inflow effect

95
Q

Define concentrating effect

A

Alveolar shrinking due to displacement of nitrogen with nitrous oxide causing a relative increase in FA to the reduced alveolar volume

96
Q

How does the concentrating effect occur

A
  • Nitrogen is the primary gas in the alveolus at RA
  • Nitrous oxide is 34 times more soluble in blood than nitrogen
  • When nitrous oxide is introduced into the lung, the volume of N2O going from alveolus to pulmonary blood is greater than nitrogen moving in the opposite direction
  • This causes alveolar shrinkage, reducing volume and increasing relative FA increase
97
Q

Why does the concentrating effect explain the difference in nitrous oxide vs desflurane rate of FA/FI rise

A

Even though desflurane is less soluble than nitrous oxide, N2O causes a shrinking effect of the alveoli, decreasing alveolar volume and increasing the relative FA.

This makes the FA/FI curve increase faster

98
Q

Define augmented flow

A

Following the concentrating effect and reduced alveolar volume, subsequent breath causes increased inflow of tracheal gas with anesthetic. The new breath replaces the lost alveolar volume and increases alveolar ventilation AUGMENTING FA

99
Q

Describe the ventilation effect

A

Describes how changes in alveolar ventilation can affect the rate of rise of FA/FI

100
Q

How does the ventilation effect alter rate of rise of FA/FI

A

The greater the alveolar ventilation, the greater the FA/FI rise

In spontaneous ventilating patients, as anesthetic deepens, alveolar ventilation decreases
Reduced anesthetic agent is input to alveolus

101
Q

Define the second gas effect

A

Administering one gas during anesthetic induction (N2O) will hasten the onset of a second gas (volatile anesthetic)

102
Q

Define diffusion hypoxia

A

Movement of N2O from the tissue back into the alveoli during emergence
This dilutes alveolar O2 and CO2 which leads to transient hypoxemia and hypocarbia

103
Q

Describe how the second gas effect works

A

When N2O is given with a second gas, the srhinkage of the alveoli d/t rapid N2O uptake causes relative increase in 2nd gas concentration in alveoli

104
Q

Which volatile anesthetics benefit most from the second gas effect

A

those with higher blood:gas solubility

Iso > sevo > des

105
Q

Up to how much N2O can be absorbed in the gas-containing areas of the body

A

30 L in 2 hrs

106
Q

What causes diffusion hypoxia with N2O

A

The temporary dilution of O2 and CO2 in the alveolus by large volumes of eliminating N2O

107
Q

How is diffusion hypoxia treated

A

Give lower FiO2

100 FiO2 may cause absorption atelectasis from higher O2

108
Q

On induction, which volatile agents are affected most by right-to-left cardiac shunt and why

A

Lower solubility gases
Because it takes longer for the FA/FI to equilibrate d/t poor uptake of lower soluble agent

Des > sevo > iso

109
Q

Why is inhaled induction slower when a right-to-left shunt is present

A

Because a fraction of blood bypasses lungs. This blood does not pick up O2 or anesthetic agents and dilutes the non-shunted fraction of oxygenated/anesthetized blood

110
Q

What are 5 examples of right-to-left shunt

A
  1. Tetralogy of Fallot
  2. Foramen ovale
  3. Eisenmenger’s syndrome
  4. Tricuspid atresia
  5. Ebstein’s anomaly
111
Q

How is an inhaled vs IV induction affected by left-to-right shunting

A

IV induction will be slower d/t recirculation of agents in the lungs

APEX Pharmacology (8 decks)

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