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Pharm of Inhalates

Pharm of Inhatation Agents

What is the partial pressure of a gas? The force exerted by the gas on the liquid it is dissolved in.
Partial Pressure of gas A force that attempts to drive molecules out of a solution and into the gas phase.
PA Alveolar Partial Pressure
Pb Brain Partial Pressure
Pa Arterial Blood
Why is the PA used as an index of the depth of anesthesia? It is an indirect measure of Pb, therefore is used to index depth of anesthesia
Is a factor that will effect the partial pressure gradients necessary for anesthesia? Transfer of inhaled anesthetic from machine to alveoli (anesthetic input)
Is a factor that will effect the partial pressure gradients necessary for anesthesia? Transfer of inhaled anesthetic from alveoli to arterial blood
Is a factor that will effect the partial pressure gradients necessary for anesthesia? Transfer of inhaled anesthetic from arterial blood to brain (anesthetic loss)
What factor will effect alveolar partial? Input into the alveoli minus the loss into the arterial blood.
Input factor Inspired partial pressure
Input factor Alveoli ventilation
Input factor Characteristics of breathing
Input factor Functional residual capacity
loss factor blood gas partition coefficient
loss factor cardiac output
loss factor alveolar to venous partial pressure difference
How does the inspired concentration of inhaled anesthetic effect the rate of increase of the alveolar concentration? A high PI (Inhaled partial pressure) from the anesthetic machine is needed during initial administration to offset the impact of uptake. Time helps accelerate induction of anesthesia.
Second gas effect ability of high volume uptake of one gas to accelerate the rate of increase on PA of a concurrently administered companion gas
Second gas effect simultaneous adm. of slower agent (halothane) with a faster drug (nitrous oxide) in high concentrations can speed the onset of the slower agent.
How does the inspired concentration of inhaled anesthetic effect the rate of increase of the alveolar concentration? A high PI (inhaled partial pressure) from the anesthesia machine is needed during initial adm. to offset the impact of uptake. This helps accelerate induction of anesthesia.
How does alveolar ventilation effect the rate of the increase in PA? Increased ventilation promotes input of inhaled anesthetic to offset uptake into blood.
Increased ventilation net effect is more rapid rate of increase in the PA and thus an increase in induction
Controlled ventilation as hyperventilation and decreased venous return accelerates rate of increase in PA by increased input (increased VA) and decreased uptake (decreased cardiac output)
Spontaneous ventilation of inhaled anesthesia produces a dose dependent depressant effect on alveolar ventilation
Spontaneous ventilation has a protective negative feedback mechanism that prevents excessive depth of anesthesia when ventilation is decreased
Spontaneous ventilation when concentration of partial pressure in the brain decreases to a certain threshold then ventilation increases to deliver more anesthesia
Mechanical ventilation the protective mechanism against development of an excessive depth of anesthesia is lost
Mechanical ventilation it may be appropriate to decrease the PI of volatile anesthesia to maintain PA similar to spontaneous
Volume of Anesthetic Breathing System acts as a buffer to slow the attainment of PA
Solubility of inhaled anesthetics in the rubber or plastics components of the Breathing System initially slow the rate at which PA rises, and at conclusion of anesthesia may slow the rate at which PA decreases.
Gas inflow from anesthetic machine helps to negate the buffering effect
Subsequent reuse of same breathing system can lead to malignant hyperthermia
What is FRC? Functional residual capacity
The greater the alveolar ventilation to FRC ratio the more rapid is the rate of increase in PA
The greater the alveolar to FRC ratio the quicker the induction
Arterial tension is directly dependent on both the rate and depth of ventilation
An increase in ventilation can increase arterial tension of anesthetics of moderate to high blood solubility (halothane) but only slightly increase that of one with low blood solubility (nitrous oxide)
What factors of pulmonary ventilation effect the rate of PA hyperventilation or hypoventilation
hyperventilation by mechanical control increases the speed of induction with inhaled anesthetics that would normally have a slow onset
depression of ventilation may slow onset of anesthesia of SOME inhaled agents
increase in pulmonary blood flow decreases the induction rate
in shock patients decreased CO and increased ventilation may accelerate the induction process
slows induction rate more soluble gases
low blood solubility few molecules are needed to raise its partial pressure and the arterial tension rises quickly
Intermediate soluble Isoflurane
Poorly Soluble Nitrous Oxide
Poorly Soluble Desflurane
Poorly Soluble Sevoflurane
blood:gas PC Isoflurane 1.46
brain:blood PC Isoflurane 1.6
muscle:blood PC Isoflurane 2.9
fat:blood PC Isoflurane 44.9
oil:gas PC Isoflurane 98
blood:gas PC Nitrous Oxide 0.46
brain:blood PC Nitrous Oxide 1.1
muscle:blood PC Nitrous Oxide 1.2
fat:blood PC Nitrous Oxide 2.3
oil:gas PC Nitrous Oxide 1.4
blood:gas PC Desflurane 0.42
brain:blood PC Desflurane 1.3
muscle:blood PC Desflurane 2
fat:blood PC Desflurane 27.2
oil:gas PC Desflurane 18.7
blood:gas PC Sevoflurane 0.69
brain:blood PC Sevoflurane 1.7
muscle:blood PC Sevoflurane 3.1
fat:blood PC Sevoflurane 47.5
oil:gas PC Sevoflurane 55
oil gas PC parallels anesthetic requirements
MAC 150/oil:gas PC
150 constant average value of the oil:gas solubility and MAC for several inhaled anesthetics with widely divergent lipid solubilities
high cardiac output results in rapid uptake which slows PA
low cardiac output speeds up PA since there is less uptake into the blood
Alveolar to venous partial pressure differences tissue uptake of the inhaled anesthetics
highly perfused tissue brain, heart, kidneys
equilibrate rapidly with PA vessel rich group (high perfused)
poorly perfused tissues skeletal muscle
how inhalant agents are eliminated once inhalant agents of gas ceases the alveoli-blood-brain gradients are reversed and the pulmonary epithelium becomes the channel of elimination
drug characteristic has greatest effect on elimination lower the solubility the faster the rate of elimination
drug characteristic that effects elimination higher the solubility, the higher the extent of accumulation over the same exposure of time
how inhalant agents are metabolized liver metabolism is significant for halothane (15%) but only 2-5% for enflurane and 0.2% for isoflurane
MAC that concentration at 1 atmosphere pressure which causes immobility in 50% of patients when exposed to a noxious stimuli
1.3 MAC effective in 99% of patients
MAC bar the dose that blocks adrenergic and cardiovascular response in 50% of individuals
increases MAC hyperthermia
increases MAC chronic alcohol use
increases MAC drug induced increases in CNS catecholamine levels (MAOI, cocaine, ephedrine, levodopa)
increases MAC hypernatremia
increases MAC hyperthyroid
decreases MAC hypothermia
decreases MAC increasing age
decreases MAC pre-op meds
decreases MAC drug induced decreases in CNS cathecolamine levels
decreases MAC alpha 2 agonist
decreases MAC acute alcohol ingestion
decreases MAC post-partum (returns to normal in 24-72 hrs)
decreases MAC pregnancy
decreases MAC lithium
decreases MAC neuraxial opioids
decreases MAC lidocaine
decreases MAC hypoxia
decreases MAC blood pressure < 40mmHG
decreases MAC cardiopulmonary bypass
decreases MAC hyponatremia
decreases MAC anemia
decreases MAC metabolic acidosis
decreases MAC opioids
decreases MAC opiod agonist-antagonist
decreases MAC diazepam
decreases MAC methyldopa
decrease MAC reserpine
decreases MAC chronic dextroamphetamine
decreases MAC alpha-2 agonist
decreases MAC lithium
decreases MAC ketamine
decreases MAC pancuronium
decreases MAC physostigmine (10x clinical dose)
decreases MAC lidocaine
decreases MAC chlorpromazine
decreases MAC verapamil
decreases MAC hydroxyzine
decreases MAC ^9 tetrahydrocanabinol
Isoflurane vapor pressure 240
Desflurane vapor pressure 681
Sevoflurane 160
Isoflurane MAC 1.2
Desflurane MAC 6
Sevoflurane MAC 2
highly perfused tissues equilibrate rapidly with the Pa.
after 3 time constants 95% of the returning venous blood is at the same partial pressure as the Pa
uptake of gas is decrease after 3 time constants
continued uptake of gases after saturation of vessel rich groups leads to anesthesia of the skeletal and fat tissues
sustained tissue uptake of the anesthestic into the large tissue mass (skeletal/fat) causes the returning venous blood to be at a lower partial pressure than the Pa
when the returning venous blood is at a lower partial pressure than the Pa the (alveolar to venous) Av-D difference is maintained and the uptake from the lungs continues for several hours.
Created by: albaker32