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APEX > Pharmacology: Volatile Anesthetics, pharmacokinetics > Flashcards

Pharmacology: Volatile Anesthetics, pharmacokinetics Flashcards

1
Q

Describe the chemical structure of Isoflurane?

A

5 fluorine atoms + 1 chlorine atom

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2
Q

Describe the chemical structure of Desflurane?

A

6 fluorine atoms

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3
Q

Describe the chemical structure of Sevoflurane?

A

7 fluorine atoms

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4
Q

Which two volatile gases contain Chiral carbons?

A

Desflurane and Isoflurane

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5
Q

Which Volatile gases are Alkanes?

A

Halothane and Chloroform

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6
Q

What does the addition of the Cl atom do to Isoflurane?

A

increases potency
increases blood and tissue solubility

(2x as potent as sevo and 5x as potent as des)

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7
Q

What is the difference between Desflurane and Isoflurane chemically?

A

The chlorine atom on Isoflurane has been replaced with a fluorine atom making Desflurane fully fluorinated

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8
Q

What does full fluorination do to Desflurane in relation to:
Potency
Vapor pressure
Resistance to biotransformation

A

decreases potency (decreased oil : gas solubility) which increases MAC

increased vapor pressure due to decreased intermolecular attraction which now requires a heated vaporizer

increased resistance to biotransformation (decreased metabolism) Thus decreased trifluoroacetate makes hepatitis extremely unlikely

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9
Q

Fluorination tends to reduce potency, what’s the deal with Sevoflurane?

A

heavily fluorinated but still 3x as potent as Desflurane, most likely due to the bulky propyl side chain

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10
Q

Vapor pressure is directly proportional to what?

A

Temp.

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11
Q

At a higher altitude what occurs with boiling?

A

boiling will occur at a lower temperature at a higher altitude as a function of reduced atmospheric pressure

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12
Q

What is Dalton’s law?

A

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

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13
Q

The depth of anesthesia is determined by the partial pressure of what?

A

anesthetic agent in the brain NOT the volume percent (volume percent is what you set at the vaporizer dial)

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14
Q

What is the problem with the Tech. 6 vaporizer?

A

It does not adjust for elevations above sea level like the other vaporizers do. Thus at higher elevations you will be under dosing your Desflurane.

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15
Q

What is the formula for partial pressure of a particular gas?

A

vol% x total gas pressure = PP of that gas

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16
Q

What is atmospheric pressure at sea level vs in Denver?

A

sea level is 760 mm Hg

Denver is 620 mm Hg

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17
Q

Which VA is not stable in hydrated soda lime?

A

Sevoflurane this is why we have a min. fresh gas flow amount for Sevo.

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18
Q

What compound does Sevo produce when not stable?

A

Compound A

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19
Q

When does Desflurane and Isoflurane become unstable and what are their by products?

A

Desiccated soda lime and can produce carbon monoxide (des > iso)

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20
Q

Tell me the vapor pressure of VA?

238, 157, 669, 38,770

A 
sevo = 157
Des = 669
Iso = 238
N20 = 38,770
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21
Q

Tell me the boiling point of each VA?

22, 49, 59, -88

A 
Sevo = 59
Des = 22
Iso = 49
N20 = -88
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22
Q

Tell me the molecular weight of each VA?

44, 184, 200, 168

A 
Sevo = 200
Des = 168
Iso = 184
N20 = 44
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23
Q

A polar solute will be more soluble in what type of solvent?

A

hydrophilic (water)

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24
Q

A non polar solute will be more soluble in what type of solvent?

A

lipophilic (fat)

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25
Q

What does the partition coefficient measure?

A

solubility, it describes the relative solubility of a solute in 2 different solvents

26
Q

What does the blood: gas partition coefficient describe?

A

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

27
Q

What is the blood: gas solubility (partition coefficient) of the major gases that we use?

A 
Sevo = 0.65
Des = 0.42
Iso = 1.46
N2O = 0.46
28
Q

What is used as a surrogate for anesthetic measurement in the brain?

A

alveolar concentration (FA) is used as a surrogate

29
Q

What is the progression of anesthetic gas from the vaporizer to the brain?

A

leaves the vaporizer (FI), then to the lungs (big A for alveoli (FA)) then to the blood (little a for arterial (uptake)) then to the brain

30
Q

What distributes anesthetic agent throughout the body?

A

CO known as distribution

31
Q

The speed of induction is a function of solubility of an anesthetic agent, explain this in terms of low and high solubility?

A

low solubility allows for less uptake in the blood which leads to an increased rate of rise and a faster equilibration of FA/FI and finally a faster onset of that anesthetic gas.

high solubility leads to more uptake into the blood and a slower rate of rise leading to a slower equilibration of FA/FI and a slower onset of that gas.

32
Q

What is it about an anesthetic gas in the blood that equates to a greater effect at the brain?

A

the partial pressure of that gas (lower solubility is better)

33
Q

A higher amount of anesthetic dissolved in the blood equals a greater or lesser effect on the brain?

A

lesser effect on the brain (slower onset)

34
Q

on the FA/FI curve tell me which gas has the highest rise of FA/FI to the lowest rate of rise?

A

N20 is the fastest rate of rise
Desflurane
Sevoflurane
Isoflurane is the slowest rate of rise

35
Q

Desflurane has a lower blood: gas partition coefficient than N2O yet the rate of rise FA/FI for N20 is higher, explain this?

A 
Des = 0.42
N20 = 0.46

Due to the concentrating effect

Nitrous oxide when introduced to the lungs will go from the alveolus to the pulmonary blood in a much higher amount than nitrogen leaving in the opposite direction, thus the alveolus shrinks. The reduction in alveolar volume causes a relative rise in FA (decreased FRC)

36
Q

Determinants of delivery to the alveoli factors?

A 
setting on the vaporizer
time constant of the delivery system
anatomic dead space
alveolar ventilation
functional residual capacity
37
Q

Determinants of Removal from the alveoli factors?

A

solubility of anesthetic in the blood (blood: gas partition coefficient)

cardiac output

partial pressure gradient between the alveolar gas and the mixed venous blood

38
Q

To increase FA/FI do you want more or less wash in, and more or less uptake?

A

To increase FA/FI you want to increase wash in and decrease uptake this would = faster onset

39
Q

What would increased wash in look like?

A 
high fresh gas flow
high alveolar ventilation 
low FRC
low time constant
low anatomic dead space
40
Q

what would decreased wash in look like?

A 
low fresh gas flow
low alveolar ventilation 
high FRC
high time constant
high anatomic dead space
41
Q

what are the 4 tissue groups for distribution of anesthetics?

A

VRG
muscle group
fat group
vessel poor group

42
Q

How much Cardiac output % does each tissue group receive?

A

VRG = 75%
Muscle = 20%
Fat = 5%
Vessel poor group = <1%

43
Q

What body mass % does each tissue group take up?

A

VRG = 10%
Muscle = 50%
Fat = 20%
Vessel poor group = 20%

44
Q

What does the Vessel group consist of?

A 
heart
brain
kidneys
liver
endocrine glands
45
Q

Which division of the body acts as a sink for inhaled anesthetics, capable of storing large amounts of the agent?

A

Fat

46
Q

What about N20, where does it distribute to?

A

N2O partitions nearly the same into all the compartments. Nitrous will quickly diffuse into the gas containing areas of the body such as the GI tract and the middle ear.

47
Q

What are the two clinically significant ways in which inhaled anesthetics are eliminated from the body?

A

Elimination from the alveoli is the primary mechanism

Hepatic metabolism is a 2ndary mechanism

48
Q

What is the hepatic biotransformation % of each inhalation anesthetic?

A 
N20 = 0.004%
Des = 0.02%
Iso = 0.2%
Sevo = 2-5%
49
Q

Halogenated anesthetics undergo metabolism by?

A

P450 system, primarily by CYP2E1

50
Q

Does metabolism play an important role during induction or recovery with inhalation anesthetics?

A

recovery

51
Q

Tell me about the metabolites of Desflurane and isoflurane?

A

They are metabolized to inorganic fluorides ions and trifluoracetic acid (TFA). TFA even in this small amount could precipitate an immune mediated hepatic dysfunction, especially in a patient with previous TFA exposure.

(TFA is the reason Halothane causes hepatitis)

52
Q

When sevoflurane is metabolized it results in the liberation of inorganic fluoride ions, what is the concern here?

A

theoretical concern of fluoride induced high output renal failure which is unresponsive to vasopressin

53
Q

Signs of high output renal failure include?

A 
polyuria
hypernatremia
hyperosmolarity
increased plasma creatinine
inability to concentrate the urine
54
Q

Is N20 metabolized by the body?

A

not metabolized by the body for all purposes

55
Q

Does sevoflurane produce compound A all on its own or only when exposed to soda lime?

A

only when exposed to soda lime (more so when the soda lime is desiccated)

56
Q

What are the two components to the concentration effect?

A

concentrating effect

augmented gas inflow

57
Q

How much more soluble is nitrous oxide in the blood than nitrogen?

A

34 x

58
Q

What is the ventilation effect?

A

How changes in alveolar ventilation can affect the rate of rise of FA/FI.

In a spontaneously ventilating patient as the anesthetic level rises the alveolar ventilation decreases and this decreases the anesthetic input to the alveolus - its is protective to min. the risk of anesthetic overdose.

59
Q

The greater the alveolar ventilation the greater the rise of what?

A

FA/FI

60
Q

How do Right to left shunts affect IV inductions?

A

R-L intracardiac shunt produces a faster IV induction (blood bypasses the lungs and travels to the brain faster)

61
Q

How does a R-L intracardiac shunt affect inhaled anesthetics?

A

lower solubility agents such as desflurane will be affected most.
There will be a reduction of the partial pressure of the anesthetic gas due to dilution (as well as PaO2) in the arterial blood.

62
Q

How does a left to right shunt affect volatile agents and IV agents?

A

meaningless effect on volatile agents

slower IV induction

APEX (18 decks)

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