1. Drug pharmacology is classically divided into pharmacodynamics (what the body does to a drug) and pharmacokinetics (what the drug does to the body). Drug pharmacokinetics has four phases: absorption (uptake), distribution, metabolism, and excretion (elimination).
2. Unique Features of Inhaled Anesthetics
   1. Speed, Gas State, and Route of Administration. The inhaled anesthetics are among the most rapidly acting drugs in existence, and when administering a general anesthetic, this speed provides a margin of safety and also means efficiency.
   2. Technically, nitrous oxide and xenon are the only true gases; the other inhaled anesthetics are vapors of volatile liquids (for simplicity, all of them are referred to as gases).
   3. A unique advantage of anesthetic gases is the ability to deliver them to the bloodstream via the patient's lungs.
3. Physical Characteristics of Inhaled Anesthetics (Table 17-1: Physiochemical Properties of Volatile Anesthetics and Table 17-2: Tissue Groups and Pharmacokinetics)
   1. The goal of delivering inhaled anesthetics is to produce the anesthetic state by establishing a specific concentration (partial pressure) in the central nervous system (CNS). This is achieved by establishing the desired partial pressure in the lungs that ultimately equilibrates with the brain and spinal cord.
   2. At equilibrium, the CNS partial pressure equals the blood partial pressure, which equals alveolar partial pressure.
4. Gases in Mixtures. For any mixture of gases in a closed container, each gas exerts a pressure proportional to its fractional mass (partial pressure).
5. Gases in Solutions
   1. The concentration of any one gas in a mixture of gases in solution depends on (i) its partial pressure in the gas phase in equilibrium with the solution and (ii) its solubility within that solution.
   2. The concentration of anesthetic in the target tissue depends on the partial pressure at equilibrium and the target tissue solubility.
   3. Because inhaled anesthetics are gases and because partial pressures of gases equilibrate throughout a system, monitoring the alveolar concentration of inhaled anesthetics provides an index of their effects on the brain.
6. Anesthetic Transfer: Machine to Central Nervous System (Table 17-3: Factors that Increase or Decrease the Rate of Increase of Alveolar Anesthetic Concentration (FA_A)/Inspired Anesthetic Concentration (FI_I))
7. Uptake and Distribution
   1. F_A/F_I. A common way to assess anesthetic uptake is to follow the ratio of the alveolar anesthetic concentration (F_A) to the inspired anesthetic concentration (F_I) over time (F_A/F_I) (Fig. 17-2: The increase in the alveolar anesthetic concentration (F_A) toward the inspired anesthetic concentration (F_I) is most rapid with the least-soluble anesthetics (nitrous oxide, desflurane, and sevoflurane) and intermediate with the more soluble anesthetics (isoflurane and halothane)).
   2. Distribution (Tissue Uptake). Factors that increase or decrease the rate of increase of F_A/F_I determine the speed of induction of anesthesia (see Fig. 17-2: The increase in the alveolar anesthetic concentration (F_A) toward the inspired anesthetic concentration (F_I) is most rapid with the least-soluble anesthetics (nitrous oxide, desflurane, and sevoflurane) and intermediate with the more soluble anesthetics (isoflurane and halothane) and Table 17-3: Factors that Increase or Decrease the Rate of Increase of Alveolar Anesthetic Concentration (FA_A)/Inspired Anesthetic Concentration (FI_I)).
   3. Metabolism plays little role in opposing induction but may have some significance in determining the rate of recovery.
8. Overpressurization and Concentration Effect
   1. Overpressurization (delivering a higher F_I than the F_A actually desired for the patient) is analogous to an intravenous bolus and thus speeds the induction of anesthesia.
   2. Concentration effect (the greater the F_I of an inhaled anesthetic, the more rapid the rate of increase of the F_A/F_I) is a method used to speed the induction of anesthesia (Fig. 17-3: The concentration effect is demonstrated in the top half of the graph in which 70% nitrous oxide (N₂O) produces a more rapid increase in the alveolar anesthetic concentration (F_A)/inspired anesthetic concentration (F_I) ratio of N₂O than does administration of 10% N₂O).
9. Second Gas Effect
   1. A special case of the concentration effect is administration of two gases simultaneously (nitrous oxide and a potent volatile anesthetic) in which the high volume uptake of nitrous oxide increases the F_A (concentrates) of the volatile anesthetic.
10. Ventilation Effects
    1. Inhaled anesthetics with low blood solubility have a rapid rate of increase in the F_A/F_I with induction of anesthesia such that there is little room to improve this rate of increase by increasing or decreasing ventilation (see Fig. 17-3: The concentration effect is demonstrated in the top half of the graph in which 70% nitrous oxide (N₂O) produces a more rapid increase in the alveolar anesthetic concentration (F_A)/inspired anesthetic concentration (F_I) ratio of N₂O than does administration of 10% N₂O).
    2. To the extent that inhaled anesthetics depress ventilation with an increasing F_I, alveolar ventilation decreases, as does the rate of increase of F_A/F_I (negative feedback that results in apnea and may prevent an overdose).
11. Perfusion Effects
    1. As with ventilation, cardiac output does not greatly affect the rate of increase of the F_A/F_I for poorly soluble anesthetics.
    2. Cardiovascular depression caused by a high F_I results in depression of anesthetic uptake from the lungs and increases the rate of increase of F_A/F_I (positive feedback that may result in profound cardiovascular depression).
12. Exhalation and Recovery
    1. Recovery from anesthesia, similar to induction of anesthesia, depends on the drug's solubility (primary determinant of the rate of decrease in F_A), ventilation, and cardiac output (Fig. 17-4: Elimination of anesthetic gases is defined as the ratio of end-tidal anesthetic concentration (F_A) to the last F_A during administration and immediately before beginning elimination (F_AO)).
    2. The “reservoir” of anesthetic in the body at the conclusion of anesthesia is determined by the solubility of the inhaled anesthetic and the dose and duration of the drug's administration (can slow the rate of decrease in the F_A).
    3. Pharmacokinetic differences between recovery and induction of anesthesia include the absence of overpressurization (cannot give less than zero) during recovery and the presence of tissue anesthetic concentrations present at the start of recovery (tissue concentration of zero at the start of anesthesia induction).

Inhaled Anesthetics

1. Pharmacokinetic Principles
2. Clinical Overview of Current Inhaled Anesthetics
3. Neuropharmacology of Inhaled Anesthetics
4. The Circulatory System
5. The Pulmonary System
6. Hepatic Effects
7. Neuromuscular System and Malignant Hyperthermia
8. Genetic Effects, Obstetric Use, and Effects on Fetal Development
9. Anesthetic Degradation by Carbon Dioxide Absorbers
10. Anesthetic Metabolism
11. Clinical Utility of Volatile Anesthetics
12. Pharmacoeconomics and Value-Based Decisions