CH 4 Inhaled Anesthetics PHARMACOKINETICS ONLY Flashcards
KEY POINTS FROM STOELTINGS AND LECTURE
The rate of increase of the PA toward the PI is _______ related to the solubility of the anesthetic in blood
The rate of increase of the PA toward the PI (maintained constant by mechanical ventilation of the lungs) is inversely related to the solubility of the anesthetic in blood.
What is described by Blood:Gas partition coefficient ?
the solubility of an inhaled anesthetic in the blood
What happens with the inhaled anesthetics when the blood:gas partition coefficient is high?
When the blood:gas partition coefficient is high, a large amount of anesthetic must be dissolved in the blood before the Pa equilibrates with the PA.
What is the overpressure technique?
Increasing the PI above the required maintenance for anesthesia
What technique is used to speed the induction of anesthesia? How is this achieved?
The overpressure technique
Achieved by Increasing the PI above the required maintenance for anesthesia
Sustaining a delivery of HIGH PI will result in
Anesthetic overdose
The overpressure technique can result in
Anesthetic overdose
True or False: Blood can be considered a pharmacologically inactive reservoir, the size of which is determined by the solubility of the anesthetic in blood.
True
What happens when the blood solubility is low?
Minimal amounts of inhaled anesthetic must be dissolved before equilibration is achieved; therefore, the rate of increase of PA and Pa, and thus onset-of-drug effects such as the induction of anesthesia, are rapid.
The inhalation of a constant PI of nitrous oxide, desflurane, or sevoflurane for about 10 minutes results in a PA that is ________ of the PI
≥80%
Why the overpressure technique is more readily accepted with sevoflurane than desflurane?
Because sevoflurane is less pungent than desflurane
How does a decreased solubility of volatile anesthetic would manifest in anemic patient?
Increased rate of increase in PA
Therefore a more rapid induction of anesthesia
How does fatty meals ingestion affect the solubility of inhaled anesthetics?
Ingesting fatty meals alters blood composition, resulting in ~ 20% increase in the solubility of volatile anesthetics
Blood:gas partition coefficients are altered by
- individual variations in water
-lipid and protein content - the hematocrit of whole blood.
blood:gas partition coefficients are about _____ less in blood with a hematocrit of 21% compared with blood with a hematocrit of 43%
20%
Decreased solubility reflects the decrease in lipid-dissolving sites normally provided by erythrocytes.
Solubility varies with
age
Which inhaled anesthetics solubility is about 18% less in neonates than in the elderly compared with young adults?
halothane, enflurane, methoxyflurane, and isoflurane
Which inhaled anesthetics solubility is not different in neonates and adults?
Sevoflurane and desflurane
Tissue:Blood partition coefficient
Determine the anesthetic uptake into tissues and the TIME necessary for equilibration of tissues with the Pa.
How the time of equilibration in tissue: blood coefficient is estimated?
By calculating a time constant (amount of inhaled anesthetic that can be dissolved in the tissue divided by tissue blood flow) for each tissue.
One time constant on an exponential curve represents
63% equilibration
Three-time constants on an exponential curve are equivalent to
95% equilibration
Three-time constants 5- 15 minutes
For volatile anesthetics, equilibration between the Pa and PBRAIN depends on
the anesthetic’s blood solubility and requires 5 to 15 minutes (three time constants)
What happens with the inhaled anesthetics when there is fat and low blood flow to the tissues?
Prolongation of tissue: blood coefficient
Prolongs the time required to narrow anesthetic partial pressure differences between arterial blood and fat.
Fasting before elective operations results in transport of fat to the liver, which could increase
Anesthetic uptake by this organ and modestly slow the rate of increase in a volatile anesthetic’s PA during anesthesia induction.
Oil:Gas partition coefficient and MAC estimation
Estimated MAC can be calculated as 150 divided by the oil: gas partition coefficient
The constant, 150, is the average value of the product of oil:gas solubility
Using this constant, the calculated MAC for a theoretical anesthetic with an oil: gas partition coefficient of 100 would be 1.5%
What is the blood:gas of N2O?
0.46
N20 is about _______ times greater (solubility) than of nitrogen (0.014)
34 times
What are the effects of N2 on a compliant wall gas cavity?
Expansion
What are the effects of N2 on a non-compliant wall gas cavity?
pressure build-up
increase intracavitary pressure
compliant wall gas cavity examples
intestines
pneumothorax
pulmonary blebs
air bubbles
non- compliant wall gas cavity examples
middle ear
cerebral ventricles
supratentorial space
N2O magnitude of VOLUME or Pressure increase is influenced by
Partial pressure of N2O
Blood flow to air-filled cavity
Duration of N2O administration
N2O transfer to closed gas spaces can cause
-Rapid expansion of a pneumothorax
-Increased bowel gas
- Tympanic membrane rupture
this will cause otitis and pot op N/V
-Increased intraocular gas after gas bubble placement
this can result in compression of the retinal artery=visual loss
How does cardiopulmonary bypass produce changes in blood:gas solubility?
Cardiopulmonary bypass produces changes in blood: gas solubility depending on the temperature and the priming solution.
Volatile anesthetics initiated during cardiopulmonary bypass take longer to equilibrate, where as the drugs already present are diluted; potentially decreasing the depth of anesthesia
INCREASED Cardiac Output and inhaled anesthetic uptake
-Increased CO, increases uptake
-Rate of increase of PA and induction are SLOWER
Increased CO results in more rapid UPTAKE
The rate of increase in the PA and anesthesia induction are SLOWED
DECREASED Cardiac Output and inhaled anesthetic uptake
-Decreased CO, decreased uptake
-Rate of increase of PA and induction are FASTER
Decreased CO speeds the rate of increase of the PA because there is less uptake to oppose input
Changes in cardiac output most influence the rate of increase of the PA of a_________anesthetic.
Soluble
The rate of increase of the PA of a __________ anesthetic, such as nitrous oxide, is rapid regardless of physiologic deviations of the cardiac output around its normal value.
poorly soluble
Doubling the cardiac output will _________ the uptake of soluble anesthetic from alveoli, slowing the rate of increase of the PA.
increase
decreases in cardiac output due to an excessive dose of volatile anesthetic results in an _________ in the PA, which further _________ anesthetic depth and thus cardiac depression.
decreases in cardiac output due to an excessive dose of volatile anesthetic results in an increase in the PA, which further increases anesthetic depth and thus cardiac depression.
Distribution of cardiac output will influence the
rate of increase of the PA of an anesthetic
infants have a ________ perfusion of vessel-rich group tissues than do adults and, consequently, show a ___________ rate of increase of the PA toward the PI
infants have a relatively greater perfusion of vessel-rich group tissues than do adults and, consequently, show a faster rate of increase of the PA toward the PI
How does the presence of a Right-to-Left shunt affect Pa?
The R-L shunt has dilutive effects and this result in a decreases Pa and a slower induction
When a right-to-left shunt is present, the DILUTING effect of the shunted blood on the partial pressure of anesthetic in blood coming from ventilated alveoli results in a decrease in the Pa and a slowing in the induction of anesthesia.
Which category of inhaled anesthetics will have a more pronounced impact in the presence of a R-L shunt?
The impact of a R-L shunt is more pronounced with less SOLUBLE inhaled anesthetic than with more soluble
Left-to-right tissue shunts occurs with
arteriovenous fistulas, volatile anesthetic-induced increases in cutaneous blood flow
Left-to-right tissue shunts will result in
in the delivery of blood to the lungs with a higher partial pressure
TRUE or FALSE left-to-right shunts offset the dilutional effects of a right-to-left shunt on the Pa.
TRUE
Tissue uptake affects uptake at the __________by controlling the rate of increase of the mixed venous partial pressure of anesthetic.
Tissue uptake affects uptake at the lung by controlling the rate of increase of the mixed venous partial pressure of anesthetic
Factors that determine tissue uptake
tissue solubility, tissue blood flow, and arterial-to-tissue partial pressure differences
Highly perfused tissues (brain, heart, kidneys) in the adult account for ______ % of body mass but receive ______ % of the cardiac output
<10%
75%
Which group tissue equilibrates rapidly with the Pa?
The vessel rich group tissues
Skeletal muscles and fat represent about______% of the body mass but receive only about _____% of the cardiac output
70%
25%
What does a continued uptake after saturation of VRG reflects?
entrance into skeletal muscle and fat this is a slow process
What does a continued uptake from the VRG result in?
In a continued Av-D difference for several hours
The time for equilibration of vessel-rich group tissues is more rapid for
__________ and ________than for ___________
The time for equilibration of vessel-rich group tissues is more rapid for neonates and infants than for adults
This difference reflects the greater cardiac output to vessel-rich group tissues in the very young as well as decreased solubility of anesthetics in the tissues of neonates. Furthermore, skeletal muscle bulk comprises a small fraction of body weight in neonates and infants.
VRG receives _____ of CO and accounts for _______ of body mass
75%
10%
Muscle group receives _____ of CO and accounts for _______ of body mass
19%
50%
Fat group receives _____ of CO and accounts for _______ of body mass
6%
20%
Vessel Poor group receives _____ of CO and accounts for _______ of body mass
<1%
20%
The recovery of anesthesia is depicted (show) by
The rate of decrease in the PBRAIN as reflected by the PA
P Brain represents
the partial pressure of the anesthetic in the brain, which is closely related to the depth of anesthesia
The concentration of the inhaled anesthetic in tissues depends highly on
The solubility of the inhaled drug and the duration of its administration.
Continued tissue uptake of anesthetic will depend on
The solubility of the inhaled anesthetic and the duration of anesthesia, with the impact being most important with soluble anesthetics
For which category of inhaled anesthetic the time to recovery is prolonged in proportion to the duration of anesthesia ?
For the soluble anesthetics Halothane and Isoflurane
With which category of inhaled anesthetics the impact of duration of administration on time to recovery is minimal?
With poorly soluble anesthetics Sevoflurane and Desflurane
TRUE or FALSE: There is a concentration effect during the recovery of anesthesia such as it occurs with induction
False, there is no concentration effect such as the one occurring during induction of anesthesia because it is not possible to administer less than zero
The rate of decrease of the PA during recovery from anesthesia will be _______ than the rate of increase of the PA during induction of anesthesia.
faster, more rapid
The patient’s exhaled gases containing anesthetic will be rebreathed unless fresh gas flow rates are _________ (at least ________L per minute of oxygen) after anesthesia.
Increased
5L per minute of oxygen
The pharmacokinetics of the elimination of inhaled anesthetics depends on
The length of administration and the blood-gas solubility of the inhaled anesthetic.
When comparing inhaled anesthetics recovery; the recovery is always the fastest for:
Desflurane, the most insoluble anesthestetic
The most insoluble anesthetic is
Desflurane
When comparing inhaled anesthetics recovery; the recovery is always the slowest for:
Isoflurane, the most soluble anesthetic
The most soluble anesthetic is
Isoflurane
When does Diffusion Hypoxia occur?
When inhalation of N2O is ABRUPTLY DISCONTINUED.
This will lead to a reversal of partial pressure gradients such as N2O leaves the blood to enter the alveoli
Initially during diffusion hypoxia the high-volume outpouring from N2O from blood to alveoli will dilute the
PA02
Dilution of the ______ can decrease inspiratory drive
PACO2
Diffusion hypoxia will cause dilution of
- PAO2 (the first one to be diluted)
- PACO2
The outpouring effect of nitrous oxide into the alveoli is greatest during the first ____ to ______ minutes after discontinuation at the conclusion of anesthesia
the first 1 to 5 minutes
What is done in order to prevent diffusion hypoxia from causing arterial hypoxemia at the end of the case?
Immediately giving 100% oxygen to alleviate dilutive effects (on PAO2) of N2O
What is done to alleviate dilutive effects of N2O?
Immediately giving 100% oxygen
Define Minimal Alveolar Concentration (MAC)
The concentration at 1 atm that prevents skeletal muscle movement in response to a supramaximal painful stimulus (surgical skin incision) in 50% of patients
The MAC allows a quantitative analysis of the effect, if any, of various physiologic and pharmacologic factors on anesthetic requirements
One MAC is the _________ dose
50% effective dose
Immobility produced by inhaled anesthetics is measured by
MAC
MAC is mediated principally by effects of inhaled anesthetics on
spinal cord
True or False: with inhaled anesthetics Only a minor component of immobility results from cerebral effects
true
TRUE or FALSE Decerebration change MAC
False, decerebration does not change MAC
MAC establishes
A common measure of potency (partial pressure at steady state) for inhaled anesthetics.
What is an unique feature of MAC?
Its consistency varies only 10% to 15% among individuals.
MAC awake
The concentration of anesthetic that prevents CONSCIOUSNESS in 50% of persons, is reliably about half of MAC
MAC-memory
The concentration of anesthetic that is associated with AMNESIA in 50% of patients.
Significantly less than MAC-awake.
Inhalation anesthetic requirements are affected by
age and body temperature
Age and MAC: Increasing age results in
a progressive decrease in MAC of about 6% per decade
MAC is decreased nearly _____% during pregnancy and in the early postpartum period
30%
Although MAC is reduced in parturients, there is evidence that the concentration-response in the brain is not changed. The dose of volatile anesthetic required to induce the electroencephalogram (EEG) changes expected with hypnosis are not changed in pregnancy
After postpartum period=, the MAC return to normal values in ___ to ___ hours
12 to 72 hours
Factors that increase MAC
Factors that decrease MAC
Factors that do not change/alter MAC
MAC is increased in women with natural red hair; this is due to
due to mutation of the melanocortin-1 receptor gene and increased pheomelanin concentrations
Which inhaled anesthetic MAC is affected by the use of cyclosporine? How it’s affected?
Isoflurane
Increases MAC
TRUE OR FALSE The MAC values may vary with the type of stimulus; tetanic stimulation and trapezius squeeze are considered noninvasive stimulation patterns that are relatively equivalent to surgical skin incision, although in contrast to skin incision, these events can be repeated.
TRUE
TRUE OR FALSE Tracheal intubation requires the highest MAC to prevent skeletal muscle responses and may represent a true supramaximal stimulation
TRUE
TRUE OR FALSE
The MAC values for inhaled anesthetics are additive.
For example, 0.5 MAC of nitrous oxide plus 0.5 MAC isoflurane has the same effect at the brain as does a 1 MAC of either anesthetic alone
TRUE
1 MAC dose prevents ________________ in response to a painful stimulus in 50% of patients, whereas a modest increase to about 1.3 MAC prevents __________________ in at least 95% of patients.
1 MAC dose prevents skeletal muscle movement in response to a painful stimulus in 50% of patients, whereas a modest increase to about 1.3 MAC prevents movement in at least 95% of patients.
What is the Meyer Overton Theory?
Known as the critical volume hypothesis.
Proposes that there is a correlation between lipid solubility (oil:gas) and potency
suggest that inhaled anesthetics acts on the lipid portion of nerve membranes
Steresoselectivity suggest that
inhaled anesthestics bind to specific channel proteins and not to the lipid layers
Isoflurane has been shown to act stereoselectively on neuronal channels, with the levoisomer being _______ potent than the dextroisomer
more
Ionotropic receptors are composed of
Several subunits.
γ-aminobutyric acid receptor type A (GABAA) and nicotinic acetylcholine receptors
What are metabotropic receptors?
monomeric receptors consisting of seven transmembrane segments
G proteins act as second messengers to activate other signaling molecules such as protein kinases or potassium or calcium channels
Which are the major mediators of inhibitory neurotransmission in the spinal cord and may mediate part of the immobility produced by inhaled anesthetics
Glycine receptors
GABA A and mediation of anesthetic action:
GABA A receptors do not mediate immobility produced by inhaled anesthetics.
GABAA receptors are potentiated at MACs of all clinically used volatile anesthetics, but their enhancement of GABAA receptor activation minimally influences MAC
Which is the principal excitatory neurotransmitter in the CNS?
Glutamate
Glutamate receptors include
NMDA, AMPA and KAINATE
Two-pore potassium channels are
intrinsic membrane receptor/ion channels that normally act to maintain the cell’s resting potential and responds to internal stimuli such as a change in pH
The TASK-3 receptors are
Anesthetic-sensitive receptors play a role in maintaining theta oscillations in the EEG associated with anesthesia and the duration of natural deep sleep.
Anesthetic interaction with TASK channels may contribute to anesthetic-induced neuroprotective effects in ischemia-reperfusion injury.
Sodium channels that ___________ the release of neurotransmitters may be more sensitive to anesthetics
modulate
Intravenous administration of lidocaine, which is a nonspecific sodium channel blocker,
_______________ MAC.
decreases
Hyperpolarization-activated cyclic nucleotide–gated channels
Are voltage-gated ion channels that are expressed throughout the body.
It is particularly important in regulating rhythmogenicity in heart and brain.
Inhaled anesthetics depress
inhaled anesthetics depress excitatory AMPA and NMDA receptor–mediated currents by actions independent of inhibitory GABAA and glycine receptor–mediated currents.
Why volatile anesthetics have been called total anesthetics?
Volatile anesthetics have been called total anesthetics because they can be used as a single agent to provide general anesthesia.
General Anesthesia
unconsciousness of the brain plus immobility in response to noxious stimuli
