Test 3: Pharmacokinetics & Misc Principles of INH Agents

Question 1

All methyl ethyl ethers undergo ____ metabolism.

Answer 1

Oxidative.
-Dependent on P450 system, genetic factors and chemical structure of the agent

Question 2

Which is the only agent to undergo reductive metabolism?

Answer 2

Halothane

Question 3

What is the principle objective of inhaled anesthesia?

Answer 3

To achieve a constant and optimal partial pressure of the agent.
-A series of partial pressure gradients propel INH agent across various barriers.

Question 4

What is the volume in the Bag?

Answer 4

3 Liters

Question 5

What is the volume in the CO2 Absorbent?

Answer 5

2 Liters

Question 6

What is the volume in the Circuit?

Answer 6

2 Liters

Question 7

What is PD?

Answer 7

Pressure delivered
-Coming out of vaporizer

Question 8

What is PI?

Answer 8

Pressure inspired.
-Moves through dead space of circuit and into patient.

Question 9

What is PA?

Answer 9

Pressure in the Alveoli

Question 10

What is Pa?

Answer 10

Pressure as the gas enters arterial blood

Question 11

What is Pbr?

Answer 11

Pressure in the brain.
-Can’t be measured, so we measure Et of the agent instead to determine the amount of agent present in the brain.

Question 12

What is the total volume of dead space in the circuit (bag + CO2 absorbent + circuit volume)?

Answer 12

7 Liters

Question 13

Goal: _____ Pressure to equal ______ Pressure. (Blue Box!)

Answer 13

Goal: Inspired Pressure (PI) to equal Alveolar Pressure (PA).

Question 14

What contributes to the input to the alveoli?

Answer 14

-Anesthesia machine
-Inspired Partial Pressure (PI)
-Alveolar Ventilation (coming from the body or mechanical ventilation)

Question 15

What is uptake?

Answer 15

Gas travels from the alveoli into the blood.
-Alveoli is the exchange zone.
-Gas crosses capillary beds
-Going down the gradient
-Effected by solubility of the agent, cardiac output, and the alveolar to venous partial pressure gradient.

Question 16

Doubling the cardiac output _____ the time to uptake of agent.

Answer 16

Doubling the cardiac output DOUBLES the time to uptake – makes it longer.

Question 17

What is FD, FI, FA, Fa, and Fbr?

Answer 17

Fraction Delivered
Fraction Inspired
Fraction in the Alveoli
Fraction as it enters into arterial blood
Fraction in the brain

Question 18

What is Dalton’s Law?

Answer 18

Pressure exerted by a mixture of perfect gases is the sum of the pressure by the individual gases occupying the same volume alone.

Question 19

What is Partial Pressure?

Answer 19

The contribution that one gas makes to the total pressure.

Question 20

What is Total Pressure?

Answer 20

The sum of the partial pressures of all the gases.

Question 21

End tidal of the agent equals the ___ ___ of the agent in the ______. (Blue Box!)

Answer 21

End Tidal of the agent equals the Partial Pressure of the agent in the brain.

Question 22

What is Alveolar Partial Pressure used for?

Answer 22

PA mirrors Pbr.
-After about 10-15 minutes, gas should reach the brain.
-Never exactly equal as some metabolism does occur
-Used an index to determine depth of anesthesia, recovery from anesthesia, and anesthetic potency (MAC).

Question 23

What is Equilibrium?

Answer 23

The same partial pressure between phases
-Not the same concentration.

Question 24

What does the FA/FI curve indicate?

Answer 24

Onset of action.
FA = Et of agent
FI = the inspired concentration dialed in on the vaporizer.
-Goal is to hit 1.0 (what we’re putting into patient = what is in the brain). 1.0 = equilibrium.
-Upstroke indicates onset of action.
-Position of the curve is determined by the agent’s plasma solubility.

Question 25

How does Blood:Gas coefficient correlate with onset of action?

Answer 25

The higher the B:G coefficient, the slower the onset. -If increased solubility, agent wants to hang out. Ex: Halothane.

Question 26

What is the exception to the B:G coefficient and onset of action rule?

Answer 26

N2O has technically a higher B:G coefficient than Des, but N2O is faster onset than Des. -this is due to the concentration effect, using a really high % of N2O

Question 27

List the agents in order from highest to lowest on the FA/FI curve.

Answer 27

Nitrous Oxide Desflurane Sevoflurane Isoflurane Halothane

Question 28

What factors influence tissue uptake of the anesthetic?

Answer 28

-Tissue solubility -Tissue blood flow (VRG has a lot more tissue blood flow - brain gets 75% of CO) -Pa - Pbr anesthetic partial pressure difference Gradient is between arterial blood and tissue. -Tissue is where MOA occurs -Inhalation agents need to get into brain tissue for the site of action.

Question 29

How do you calculate the tissue uptake?

Answer 29

(Brain/Blood Coefficient) x (Tissue blood flow) x (partial pressure difference) -Partition Coefficients exists for all gases for Brain:Blood and Fat:Blood -If any factor = 0 than there is no uptake

Question 30

What makes up the Vessel Rich Group (VRG)?

Answer 30

-Brain, heart, liver, kidneys, endocrine glands -10% of mass, 75% of CO -Small mass with high blood flow -Equilibration of Pa with VRG = 4-8min -Then uptake principally determined by muscle group

Question 31

Describe the Muscle and Skin Group.

Answer 31

-15% of mass, 19% of CO -Large tissue volume relative to rate of perfusion -Uptake continues long after equilibration of VRG -Equilibration of Pa with Muscle Group = 1-4hrs

Question 32

Describe the Fat Group

Answer 32

-20% of mass, 6% of CO -Rate of perfusion similar to muscle -Anesthetic solubility significantly different -Equilibration of Pa with FG >24 hrs -Does not effect onset, but can effect emergence if agent is administered >4 hrs and becomes sequestered in fat cells.

Question 33

Describe the Vessel Poor Group (VPG)

Answer 33

-Ligaments, tendons, bone, cartilage -20% of mass, 0% of CO -No anesthetic action occurs here

Question 34

What determines the elimination of the INH agent?

Answer 34

-Length of administration (highly lipid soluble agents can become sequestered if given >4 hours). The longer the agent was administered, the slower the emergence. -Solubility of the agent (elimination time is decreased with less plasma soluble agents such as Des - rapid recovery)

Question 35

What are factors that we can manipulate to speed recovery?

Answer 35

-Decreasing the concentration of the agent to eliminate rebreathing (Suppression of respiration stops and they start coming back breathing) -High fresh gas flows -Increasing the patient's ventilation

Question 36

What causes Diffusion Hypoxia?

Answer 36

When N2O is discontinued abruptly. -Reversal of partial pressure gradients -Reverse concentration effect. -High volume of N2O enters the alveoli from the capillary blood flow. This dilutes/displaces O2 from the alveoli, resulting in transient alveolar hypoxia. -Dilutes PaCO2 as well, depressing the stimulus to breathe (worsening hypoxia) -Can be avoided by administering 100% O2 at the end of the case.

Question 37

What is unique about the Tec 6?

Answer 37

-Uses electricity to maintain a high temp and pressure -39oC creating VP = 2 atmospheres

Question 38

Why does Desflurane need the Tec 6?

Answer 38

-VP of Desflurane = 664. -At atmospheric pressure, it vaporizes instantly. -Would require a very high gas flow to dilute the concentration to a patient appropriate level (safe clinical dose) -Cooling effect of vaporization of large quantities of Desflurane is great (variable bypass vaporizer cannot maintain a constant temperature)