BIOM 3090 Lecture Notes - Lecture 25: Isoflurane, Partition Coefficient, Partial Pressure
9 Jun 2018
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Delivery of inhalants from alveolar gas to blood to brain
- Delivery of drug to brain depends on several factors:
1) Solubility of drug in tissues (e.g. blood or brain) vs. alveolar gas
a. Called the blood: gas partition coefficient” (BGPC or
lambda)
i. Varies slightly between species
ii. Indicates relative solubility of the drug in tissues vs.
alveolar gas
▪ Range: For ex. at equilibrium the concentration of isoflurane
will be 1.4 x higher in tissues than in the alveolar air
▪ Onset: (if no induction drug used) & recovery are fast with
poorly soluble drugs; slow with highly soluble drugs. Occurs
for 2 reasons:
• Anesthetic effect is related to partial pressure in the
brain, and a low concentration of a poorly soluble drug
will create a high partial pressure in the tissues
▪ Partial pressures of a drug with low tissue solubility (nitrous
oxide) rise more rapidly than those of a drug that is more
soluble in tissues (halothane)
b. Partial pressure in the blood (and therefore the brain) will
not approach alveolar partial pressure until muscle and
adipose are at least partially saturated with the drug
i. Takes longer for drugs that are highly soluble in
tissues to saturate large organs such as skeletal
muscle and adipose, so onset takes longer
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Document Summary
Delivery of inhalants from alveolar gas to blood to brain. It takes longer to raise concentration to equilibrium with a highly tissue- soluble drug, because much of the drug is lost from the blood to other tissues on the way. Only after muscle and fat become partially saturated does the blood reaching the brain contain enough drug to cause unconsciousness. It also takes longer to recover from a highly tissue-soluble drug, because drug leaving other tissues keeps the blood concentration higher, longer. Isoflurane relatively poorly soluble (bgpc = 1. 4) rapid recovery (< 1 min. : elimination is also influenced by respiratory rate and pulmonary blood flow. Metabolism: extent of metabolism is related to toxicity, halothane ~ 25-40% metabolized, sevoflurane ~3-5% Isoflurane ~0. 2: metabolites harmful to liver, usually only a problem with repeated, long procedures with halothane or very long procedures with sevoflurane, cyp 2e1 is the major p450 enzyme catalyzing defluorination of concentration volatile anesthetics.
