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Apex > Unit 4 Pharmacology: Volatile Anesthetics 1: Pharmacokinetics > Flashcards

Unit 4 Pharmacology: Volatile Anesthetics 1: Pharmacokinetics Flashcards

1
Q

What are the 3 categories of inhaled anesthetics?

A

Ethers
Alkanes
Gases

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2
Q

Name 6 ethers

A 
Desflurane
Isoflurane
Sevoflurane
Enflurane 
Metholxyflurane
Ether
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3
Q

Name 2 Alkanes

A

Halothane

Chloroform

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4
Q

Name 3 gases

A

Nitrous oxide
Cyclopropane
Xenon

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5
Q

How man fluorine atoms does each of the 3 common gases have?

A

Iso: 5
DES: 6
SEVO: 7

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6
Q

Which of the 3 common volatile agents used contain chiral carbons?

A

ISO

DES

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7
Q

What is the chemical name of ISO?

A

1-chloro 2,2,2-trifluorothyl difluroromethyl ether

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8
Q

What 3 things does the chlorine atom in ISO do?

A

Increases potency

Increases blood and tissue solubility

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9
Q

What is the chemical name of DES?

A

Difluoromethyl 1,2,2,2-tetrafluoroethyl ether

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10
Q

The full fluorination (of DES) has what effects?

A

Decreases potency - decreases oil:gas solubility -> increased MAC
Increases vapor pressure - decreases intermolecular attraction -> requires heated vaporizer
Increases resistance to biotransformation - decreased metabolism -> trifluoroacetate makes an immune mediated hepatitis extremely unlikely

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11
Q

What is the chemical name of SEVO?

A

Fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether

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12
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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13
Q

How does temperature affect vapor pressure?

A

Vapor pressure is directly proportional to temperature

Increasing temperature increases vapor pressure

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14
Q

How does altitude affect boiling point?

A

At high altitude, a liquid will boil at a lower temperature as a function of the reduction in atmospheric pressure

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15
Q

Define partial pressure

A

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

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16
Q

What law states that the total gas pressure in a container is equal to the sum of the partial pressures exerted by each gas?

A

Dalton’s law

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17
Q

The depth of anesthesia is determined by _____

A

The partial pressure of anesthetic agent in the brain

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18
Q

What is setting the dial setting?

A

The volumes percent

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19
Q

What is stability?

A

The ability to resist breakdown or metabolism

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20
Q

Carbon dioxide and the liver are capable of transforming volatile anesthetics into _____

A

Toxic compounds

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21
Q

What do DES and ISO produce in desiccated soda lime? One does this more than the other.

A

Carbon monoxide

DES > ISO

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22
Q 
SEVO properties:
Vapor pressure
Boiling point
Molecular weight
Preservative
Stable in hydrated CO2 absorber
Stable in dehydrated CO2 absorber
Toxic byproduct
A 
Vapor pressure: 157 mmHg
Boiling point: 50 C
Molecular weight: 200 g/mol
Preservative: None
Stable in hydrated CO2 absorber: No
Stable in dehydrated CO2 absorber: No 
Toxic byproduct: Compound A
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23
Q

DES properties:

Vapor pressure
Boiling point
Molecular weight
Preservative
Stable in hydrated CO2 absorber
Stable in dehydrated CO2 absorber
Toxic byproduct
A 
Vapor pressure: 669 mmHg
Boiling point: 22 C
Molecular weight: 168 g/mol
Preservative: No
Stable in hydrated CO2 absorber: Yes
Stable in dehydrated CO2 absorber: No
Toxic byproduct: carbon monoxide
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24
Q

ISO properties

Vapor pressure
Boiling point
Molecular weight
Preservative
Stable in hydrated CO2 absorber
Stable in dehydrated CO2 absorber
Toxic byproduct
A 
Vapor pressure: 238 mmHg
Boiling point: 49 C
Molecular weight: 184 g/mol
Preservative: No
Stable in hydrated CO2 absorber: Yes
Stable in dehydrated CO2 absorber: No
Toxic byproduct: carbon monoxide
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25
Q

N2O properties

Vapor pressure
Boiling point
Molecular weight
Preservative
Stable in hydrated CO2 absorber
Stable in dehydrated CO2 absorber
Toxic byproduct
A 
Vapor pressure: 38,770 mmHg
Boiling point: -88 C
Molecular weight: 44 g/mol
Preservative: No
Stable in hydrated CO2 absorber: Yes
Stable in dehydrated CO2 absorber: Yes
Toxic byproduct: None
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26
Q

What is a partition coefficient?

A

A measure of solubility, describes the relative solubility in 2 different solvents

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27
Q

What is the blood: gas partition coefficient?

Formula?

A

Describes the relative solubility of an inhalation anesthetic in the blood vs in the alveolar gas when the partial pressures between the 2 compartments are equal.

Partition coefficient = anesthetic dissolved in blood / anesthetic inside the alveolus

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28
Q 
Partition coefficients for SEVO:
Blood:Gas
Brain:Blood
Muscle:Blood
Fat:Blood
Oil:Gas
A 
Blood:Gas - 0.65
Brain:Blood - 1.7
Muscle:Blood - 3.1
Fat:Blood - 47.5
Oil:Gas - 47
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29
Q 
Partition coefficients for DES:
Blood:Gas
Brain:Blood
Muscle:Blood
Fat:Blood
Oil:Gas
A 
Blood:Gas - 0.42
Brain:Blood - 1.3
Muscle:Blood - 2.0
Fat:Blood - 27.2
Oil:Gas - 19
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30
Q 
Partition coefficients for ISO:
Blood:Gas
Brain:Blood
Muscle:Blood
Fat:Blood
Oil:Gas
A 
Blood:Gas - 1.46
Brain:Blood - 1.6
Muscle:Blood - 2.9
Fat:Blood - 44.9
Oil:Gas - 91
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31
Q 
Partition coefficients for N2O: 
Blood:Gas
Brain:Blood
Muscle:Blood
Fat:Blood
Oil:Gas
A 
Blood:Gas - 0.46
Brain:Blood - 1.1
Muscle:Blood - 1.2
Fat:Blood - 2.3
Oil:Gas - 1.4
32
Q

What is FA/FI?

A

FA: the partial pressure of anesthetic inside the alveoli
FI: the concentration of anesthetic exiting the vaporizer

33
Q

Why do we measure alveolar concentration of volatile anesthetic?

A

The concentration of an agent inside the alveoli is proportional to its concentration inside the blood and this is proportional to the anesthetic inside the brain.

34
Q

What is uptake of anesthetic?

A

The buildup of anesthetic partial pressure inside the alveoli is being opposed by continuous uptake of agent into the blood

35
Q

What is distribution of anesthetic?

A

The cardiac output distributes the anesthetic agent throughout the body.

36
Q

What is the importance of solubility?

A

Speed of induction is a function of solubility:

Low solubility -> less uptake into blood -> increases rate of rise -> faster equilibration of FA/FI -> faster onset

37
Q

On FA/FI curve order from top to bottom (fastest to slowest)

A

N2O 0.46
DES 0.42
SEVO 0.65
ISO 1.46

38
Q

Why does DES have a lower blood:gas partition coefficient than N2O et the FA/FI of N2O is higher?

A

Concentrating effect

39
Q

FA is a function of what 2 things?

A
  1. The rate of deliver to the alveoli

2. The rate of removal from the alveoli

40
Q

What determines delivery to the alveoli?

A 
Setting on the vaporizer
Time constant of the delivery system
Anatomic dead space
Alveolar ventilation
Functional residual capacity
41
Q

What determines removal from the alveoli?

A

Solubility of anesthetic in the blood (blood:gas coefficient)
Cardiac output
Partial pressure gradient between the alveolar gas and the mixed venous blood

42
Q

How can you increase FA/FI?

A 
Increase wash in:
High FGF
High alveolar ventilation
Low FRC
Low time constant
Low anatomic dead space

Decrease uptake:
Low solubility
Low cardiac output
Low Pa-Pv difference

43
Q

How can you decrease FA/FI?

A 
Decrease wash in:
Low FGF
Low alveolar ventilation
High FRC
High time constant
High anatomic dead space

Increase uptake:
High solubility
High cardiac output
High Pa-Pv difference

44
Q

Tissue uptake is unique for each type of tissue, what is uptake dependent on?

A

Tissue blood flow
Solubility of the anesthetic in the tissue
Arterial blood : tissue partial pressure gradient

45
Q

What are the 4 tissue groups? How much CO does each receive vs how much body mass are they?

A

Vessel rich group: 75% of CO - 10% of body mass
Muscle & skin: 20% of CO - 50% of body mass
Fat: 5% of CO - 20% of body mass
Vessel poor group: <1% of CO - 20% of body mass

46
Q

What does the vessel rich group consist of?

A 
Heart
Brain
Kidneys
Liver
Endocrine glands
47
Q

What is the importance of the fat group?

A

Because halogenated agents are lipid soluble the fat group functions as a high capacity sink capable of sting large amounts of agent

48
Q

What does the vessel poor group consist of?

A

tendons
Ligaments
Cartilage
Bone

49
Q

What is unique about N2O uptake with these groups?

A

It partitions nearly the same in all of the compartments. It will quickly diffuse into the gas containing areas such as GI and middle ear.

50
Q

What are the 3 ways inhaled anesthetics are eliminated from the body

A
  1. Elimination from the alveoli
  2. Hepatic biotransformation
  3. Percutaneous loss
51
Q

What is the primary mechanism by which inhalation anesthetics are removed from the body? Second? Third?

A
  1. Exhalation from the lungs
  2. Hepatic metabolism
  3. Percutaneous loss - minimal and not clinically significant
52
Q

What is the % of Biotransformation of each agent?

A

N2O: 0.004
DES: 0.02
ISO: 0.2
SEVO: 2 - 5

53
Q

How are halogenated anesthetics metabolized in the liver?

A

P450 system

-primarily CYP2E1

54
Q

DES, ISO, and Halothane are metabolized by the liver into what?

A

Inorganic fluoride ions and trifluoroacetic acid (TFA)

55
Q

What is the mechanism of halothane hepatitis?

A

Up to 20% of Halothane undergoes biotransformation and a high concentration of TFA in the liver is the mechanism

56
Q

SEVO is metabolized by the liver into what?

A

Biotransformation results in liberation of inorganic fluoride ions, there is a theoretic concern of fluoride induced high output renal failure.

57
Q

What are the signs of high output renal failure?

A 
Unresponsive to vasopressin
Polyuria
Hypernatremia
Hyperolsmolarity
Increased plasma creatinine 
Inability to concentrate urine
58
Q

For all intents and purposes, N2O is NOT metabolized by the body. T/F

A

True

59
Q

How does Soda Lime contribute to the breakdown of halogenated anesthetics?

A

SEVO generates Compound A - accelerated by desiccated soda lime
DES and ISO produce carbon monoxide in desiccated soda lime

60
Q

What is the concentration effect?

A

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

61
Q

What gas is the concentration effect relevant?

A

N2O

62
Q

What are the 2 components of the concentration effect?

A

Concentrating effect

Augmented gas inflow

63
Q

What is the significance of the concentrating effect?

A

When breathing room air, nitrogen is the primary gas in the alveolus. N2O is ~ 34x more soluble in the blood than nitrogen. When N2O is introduced into the lung, the volume of N2O going from the alveolus to the pulmonary blood is much higher than the amount of nitrogen move in in the opposite direction. This causes the alveolus to shrink and the reduction in alveolar volume causes a relative increase in FA.

64
Q

What is augmented gas flow?

A

The concentrating effect temporarily reduces alveolar volume, on the subsequent breath the concentrating effect causes an increased inflow of tracheal gas containing anesthetic agent to replace the lost alveolar volume. This increases alveolar ventilation and augments FA. This is only a very temporary phenomenon because alveolar volume is restored quickly.

65
Q

What is the ventilation effect?

A

It describes how changes in alveolar ventilation can affect the rate of rise of FA/FI, the greater the alveolar ventilation the greater the rate of rise.

66
Q

In the spontaneously ventilating patient, as the anesthetic is deepened, alveolar ventilation: increases or decreases?

A

Decreases, can be thought of as a protective mechanism

67
Q

Assuming the FRC remains constant, which concept explains a temporary increase in alveolar oxygen concentration with nitrous oxide is turned on during inhalation induction?

A

Second gas effect

68
Q

What is the second gas effect?

A

The use of N2O during inhalation induction will hasten the onset of a second gas. Rapid uptake of N2O causes the alveolus to temporarily shrink, this reduction in alveolar volume and augmented tracheal inflow cause a relative increase in concentration of the second gas.

69
Q

What is diffusion hypoxia?

A

N2O was rapidly diffuse into the alveoli when it is discontinued, this volume can dilute the alveolar oxygen and carbon dioxide leading to temporary diffusion hypoxia and hypocarbia.

70
Q

How do you avoid diffusion hypoxia?

A

Administer 100% O2 for 3 - 5 minutes after N2O has been discontinued.

71
Q

How does a right-to-left shunt affect PaO2 and partial pressure of anesthetic agent int he arterial blood?

A

The lungs are bypassed by some of the blood, so PaO2 and partial pressure of VA are both reduced.

72
Q

List 5 examples of a right-to-left shunt

A 
Tetralogy of Fallot 
Foramen ovale
Eisenmenger’s syndrome
Tricuspid atresia 
Ebstein’s anomaly
73
Q

In the presence of a right-to-left shunt how are VAs affected?

A

Agents with low solubility will be more affected that agents with higher solubility. More soluble agents experience a greater degree of uptake by the blood which partially offsets the dilution effect.

74
Q

A patient has a right-to-left shunt. The rate of rise of FA/FI of which drug will be affected most?

A

DES

75
Q

How are IV agents affected by a right-to-left shunt?

A

Produces a faster IV induction because the drug bypasses the lungs and travels to the brain faster as a result.

76
Q

How are VAs affected by left-to-right shunting?

A

A left-to-right shunt will not have a meaningful effect on anesthetic uptake or induction time.

77
Q

How are IV agents affected by left-to-right shunt?

A

Produces a slower IV induction because IV agent is recirculated in the lungs.

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