Uptake and Distribution of Inhalation Anesthetics – Flashcards
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what the body does to the drug
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Define pharmacokinetics
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absorption distribution metabolism excretion
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What are the 4 parts of pharmacokinetics
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What the drug does to the body "The intrinsic sensitivity or responsiveness of receptors to a drug and the mechanisms by which these effects occur"
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Define pharmacodynamics
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from the alveoli into systemic circulation
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Where does the pharmacokinetic uptake of inhalation anesthetics occur?
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movement into the various organ systems
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What does the distribution of inhaled anesthetics refer to?
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Partial pressure gradients
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What is responsible for moving the inhaled anesthetics across various barriers in the body?
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The brain
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Where is the site of action of inhaled anesthetics?
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Dalton's Law
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What law describes how we get inhaled anesthetics to the brain?
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the total pressure of a group of gases is equal to the sum of their individual partial pressures (Ptotal = P1 + P2 + P3...)
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What is Dalton's Law?
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to achieve a constant and optimal brain partial pressure
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What is the primary action of inhaled anesthetic agents
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the net movement of gas molecules which proceed from a phase of higher concentration to a phase of lesser concentration
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What is partial pressure
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Anesthesia Gas Machine (PI) Alveoli (PA) Arterial Blood (Pa) Brain (Pbr) = tissues Venous blood (Pv) Alveoli (PA)
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What levels does partial pressure equilibrium occur?
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PI>PA>Pa>Pbr>Pv
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What is the order of partial pressures at the induction of anesthesia?
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when equilibrium is achieved among all phases PI = PA = Pa = Pbr = Pv = PA
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When does PA of an inhaled anesthetic reflect Pbr?
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alveolar partial pressure
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What pressure can become a "mirror" of brain partial pressure
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No, it means that the same PARTIAL PRESSURE exists
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Does equilibrium between pressures mean equality of concentration?
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input factors - uptake factors = alveolar concentration
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How do you calculate alveolar concentration of inhaled anesthetics?
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1) inspired partial pressure (PI) 2) Alveolar ventilation 3) Components of anesthetic breathing system
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What are 3 input factors
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1) solubility 2) cardiac output 3) tissue uptake
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What are 3 uptake factors
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inspired partial pressure (PI)
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Which input factor would "concentration effect" fall under?
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how the inspired partial pressure (PI) of an anesthetic affects the rate at which the alveoli partial pressure (PA) equilibrates with the inspired partial pressure (PI)
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What does the concentration effect describe?
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an increase in inspired partial pressure (PI) concentration. The greater PI the faster the speed at which PA would increase and equilibrates. (this is the concentration effect)
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Increasing the concentration set on the vaporizer would result in what?
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1) Concentration effect 2) Over-pressuring 3) The Second Gas Effect
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What are 3 factors that influence inspired partial pressure?
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Over-pressuring
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What is a way to overcome gradients to achieve equilibrium of PI and Pbr?
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Over-pressuring
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What method can be used to increase PI is analogous to an IV bolus?
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By setting a higher than normal concentration at the vaporizer. This will offset the uptake and speed the equilibrium between PI and Pbr
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How do you achieve over-pressuring?
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the ability of a large volume of one gas to speed the rate of rise of the PA of a second gas
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What is the second gas effect?
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N2O
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What is the carrier gas used the achieve the second gas effect?
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Desflurane - very low blood gas coefficient (already wants to go to the brain and out of the blood)
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Which volatile agent is dangerous to overpressure with and why?
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Increasing alveolar ventilation increases equilibration of PI and PA
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Would increasing or decreasing alveolar ventilation speed the rate in which PI will equilibrate with PA?
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Set ventilator at 14 instead of 6 - the faster you breath the more you bring in
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How do you increase alveolar ventilation?
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1) dead space volume 2) solubility of the agent in the tubing 3) fresh gas flow
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What components of the breathing system effect input?
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Up to 6 liters
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How much dead space volume can you have in a breathing circuit?
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turn up fresh gas flow - the higher the fresh gas flow the faster equilibrium will occur
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How can you overcome the anesthesia breathing circuit characteristics?
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1) Agent solubility 2) Cardiac output 3) Tissue uptake
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What factors affect uptake?
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Uptake = Cardiac Output (Q) x concentration gradient (alveolar to venous partial pressure difference) x blood to gas solubility Note:no uptake occurs if any of these = 0
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What is the equation for uptake?
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blood-gas partition coefficient (BGPC)
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How is solubility of an anesthetic agent measured?
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the distribution ratio of molecules (agent) at equilibrium (when the partial pressures have equilibrated between arterial blood and gas)
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What is BGPC?
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a RAPID equilibration between the alveolus and the arterial blood
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What does a low BGPC mean?
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12
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BGPC of methoxyflurane
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2.54
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BGPC of Halothane
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1.90
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BGPC of Enflurane
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1.46
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BGPC of isoflurane
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0.69
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BGPC Sevoflurane
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0.46
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BGPC Nitrous Oxide
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0.42
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BGPC Desflurane
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rapid
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Would a low BGPC result in slow or rapid equilibration and speed of induction?
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SLOW! Results in rapid uptake by the circulation (wash out) so that the rate of rise in the PA and speed of induction is slow - think more blood dilutes
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If you have increased CO what will happen to the speed of induction?
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FAST! results in a slow uptake by the circulation so that the rate of equilibration between PA and Pa is enhanced
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If you have decreased CO what will happen to the speed of induction?
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Pa to Pv partial pressure difference
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What partial pressure difference describes tissue uptake?
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DECREASE!
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Will tissue uptake result in a decrease or increase in PA
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DECREASE PA and thus Pbr
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Will Agents with high tissue solubility partition coefficients increase or decrease PA and Pbr?
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Cardiac Output - the higher the % of cardiac output to a specific tissue group the quicker the equilibration.
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What factor can increase the equilibration between Pa and Pv?
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Brain Heart Liver Kidneys
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What tissues are known as the vessel rich group?
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Vessel Rich Group
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Which group equilibrates Pa and Pv the quickest?
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75% CO at 10% body weight
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How much CO does the Vessel Rich Group Receive?
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Muscle at 19% CO and 50% body weight
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What group receives the next largest CO after the VRG?
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6% CO at 20% body weight
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How much CO does Fat get?
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Vessel rich group Muscle Fat Vessel Poor Group: Bone and cartilage
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What are the areas considered in tissue uptake
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1st: rapid rise of FA toward FI before uptake begins (no concentration gradient exists) Bend: rapid uptake into the blood and distribution to vessel-rich group 2nd seg: dist and uptake muscle 3rd seg: dist and uptake fat
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FA/FI Curve name what each represents (1st segment, bend, 2nd segment, 3rd segment)
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Time constants
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How do we measure inhalation agents?
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The time until a 63% change of the system toward equilibrium occurs
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What is the time constant for inhaled anesthetics defined as?
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By tissue groups: Capacity of tissue/blood flow to tissue
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How do we calculate time constants
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Lambda or tissue to blood solubility for a specific tissue bed x K ( a constant representing 100 ml of tissue)
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What is the Definition of capacity?
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flow/100 ml of tissue/minute
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How is blood flow to a tissue defined?
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low tissue to blood partition coefficient- takes longer to equilibrate because high percentage of body composition combined with lower perfusion of 3 ml per 100 ml of muscle tissue
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Why does the muscle group take longer to equilibrate?
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the movement of inhalation anesthetic into muscle and fat (slow in, slow out)
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What can be the potential cause of post-aneshteic sedation?
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About 2 hours
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How long does it take for muscle equilibration to occur?
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4 hours and up
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how long does it take for fat equilibration to occur?
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PI<PA<Pa<Pbr<Pv
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What would the partial pressures look like during reversal?
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the rate at which PA decreases over time
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How do you define recovery?
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1) Inspired partial pressure - PI<PA 2) Tissue to venous partial pressure difference Pbr<Pv 3) Alveolar ventialtion 4) Cardiac Output 5) Metabolism of Agent
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What are factors that influence a decline in PA during recovery?
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20%
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What percentage of halothane is metabolized?
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3%
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what percentage of enflurane is metabolized?
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0.2%
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What percentage of isoflurane is metabolized?
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0.02%
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What percentage of Desflurane is metabolized?
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3-5%
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What percentage of Sevoflurane is metabolized?
