Test 3: Pharmacokinetics & Misc Principles of INH Agents Flashcards
All methyl ethyl ethers undergo ____ metabolism.
Oxidative.
-Dependent on P450 system, genetic factors and chemical structure of the agent
Which is the only agent to undergo reductive metabolism?
Halothane
What is the principle objective of inhaled anesthesia?
To achieve a constant and optimal partial pressure of the agent.
-A series of partial pressure gradients propel INH agent across various barriers.
What is the volume in the Bag?
3 Liters
What is the volume in the CO2 Absorbent?
2 Liters
What is the volume in the Circuit?
2 Liters
What is PD?
Pressure delivered
-Coming out of vaporizer
What is PI?
Pressure inspired.
-Moves through dead space of circuit and into patient.
What is PA?
Pressure in the Alveoli
What is Pa?
Pressure as the gas enters arterial blood
What is Pbr?
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.
What is the total volume of dead space in the circuit (bag + CO2 absorbent + circuit volume)?
7 Liters
Goal: _____ Pressure to equal ______ Pressure. (Blue Box!)
Goal: Inspired Pressure (PI) to equal Alveolar Pressure (PA).
What contributes to the input to the alveoli?
-Anesthesia machine
-Inspired Partial Pressure (PI)
-Alveolar Ventilation (coming from the body or mechanical ventilation)
What is uptake?
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.
Doubling the cardiac output _____ the time to uptake of agent.
Doubling the cardiac output DOUBLES the time to uptake – makes it longer.
What is FD, FI, FA, Fa, and Fbr?
Fraction Delivered
Fraction Inspired
Fraction in the Alveoli
Fraction as it enters into arterial blood
Fraction in the brain
What is Dalton’s Law?
Pressure exerted by a mixture of perfect gases is the sum of the pressure by the individual gases occupying the same volume alone.
What is Partial Pressure?
The contribution that one gas makes to the total pressure.
What is Total Pressure?
The sum of the partial pressures of all the gases.
End tidal of the agent equals the ___ ___ of the agent in the ______. (Blue Box!)
End Tidal of the agent equals the Partial Pressure of the agent in the brain.
What is Alveolar Partial Pressure used for?
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).
What is Equilibrium?
The same partial pressure between phases
-Not the same concentration.
What does the FA/FI curve indicate?
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.
How does Blood:Gas coefficient correlate with onset of action?
The higher the B:G coefficient, the slower the onset.
-If increased solubility, agent wants to hang out. Ex: Halothane.
What is the exception to the B:G coefficient and onset of action rule?
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
List the agents in order from highest to lowest on the FA/FI curve.
Nitrous Oxide
Desflurane
Sevoflurane
Isoflurane
Halothane
What factors influence tissue uptake of the anesthetic?
-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.
How do you calculate the tissue uptake?
(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
What makes up the Vessel Rich Group (VRG)?
-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
Describe the Muscle and Skin Group.
-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
Describe the Fat Group
-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.
Describe the Vessel Poor Group (VPG)
-Ligaments, tendons, bone, cartilage
-20% of mass, 0% of CO
-No anesthetic action occurs here
What determines the elimination of the INH agent?
-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)
What are factors that we can manipulate to speed recovery?
-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
What causes Diffusion Hypoxia?
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.
What is unique about the Tec 6?
-Uses electricity to maintain a high temp and pressure
-39oC creating VP = 2 atmospheres
Why does Desflurane need the Tec 6?
-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)
