Medical Pharmacology Topics
| Preliminary Outline |
Inhaled Anesthetics Gaseous  Nitrous Oxide
Volatile Liquids Sevoflurane Desflurane Isoflurane Halothane Enflurane |
The mechanism of inhaled anesthetics is unknown. They probably act at several sites. The skeletal muscle response may be mediated by the spinal cord. Amnesia most likely results from action in the brain. One theories attribute their effect to receptor binding. Another theory points to their hydrophobic nature, which may allow them to dissolve into cell membranes, expand them and inhibit synaptic transmission.
The minimum alveolar concentration (MAC) of inhaled anesthetics is that which prevents muscle movement to a surgical incision in 50% of patients. MAC values for combinations of agents are additive. 1.3 MAC prevents movement in almost all patients.
Of the modern inhaled anesthetics, nitrous oxide is the only gas. Sevoflurane, desflurane, isoflurane halothane and enflurane are volatile liquids. Halothane and enflurane use is declining, although halothane is still used extensively outside the USA.
Inhaled anesthetics have pharmacological effects on the CNS, circulation and ventilation. They all produce cerebral vasodilation and increased cerebral blood flow. Autoregulation of cerebral blood flow is preserve by isoflurane but not by halothane (relevant during brain surgery). Enflurane can produce seizure-like activity.
All volatile anesthetics decrease blood pressure. Substituting nitrous oxide for a portion of one of the volatile anesthetics causes less of a decease in blood pressure than the volatile anesthetic alone. Isoflurane, desflurane and Sevoflurane decrease heart rate and systemic vascular resistance. Halothane decreases cardiac output.
All inhaled anesthetics increase respiratory rate and decease tidal volume, with a net decrease in minute ventilation and increase in the arterial partial pressure of carbon dioxide. This effect is lessen with nitrous oxide. All inhaled anesthetics decrease airway resistance (are bronchodilators). Isoflurane and desflurane are modest airway irritants, therefore a barbituric and muscle relaxant are administered first intravenously. Sevoflurane and halothane are not airway irritants, and are preferred for pediatric patients.
The ideal inhaled anesthetic should:
Halothane, enflurane and isoflurane have an intermediate blood:gas partition coefficients, while nitrous oxide, desflurane and Sevoflurane have the lowest blood:gas partition coefficients.
The blood:gas partition coefficient of nitrous oxide is 34 times that of nitrogen, so it can leave blood and enter air-filled cavities more rapidly than nitrogen can move from the cavity to blood. This is a problem for patients with pneumothoraces (air between lung and chest), venous air emboli, and severe bowel obstruction.
Metabolism plays very little role in the reduction of alveolar partial pressure (PA) for the comonly used, less soluble agents like sevoflurane, desflurane and isoflurane. Ventilation is the primary mechanism of elimination. About 5% of sevoflurane is metabolized by CytP450. Halothane is eliminated by both ventilation and metabolism (15-25%), the later by CytP450 oxidation in the liver.
Halothane metabolites include fluorides, chlorides and bromides, usually at concentration too low to cause toxic effects. "Halothane hepatitis" may lead to massive hepatic necrosis and death, and may be immune-mediated. Risk factors include female gender, middle age, obesity and repeat exposure to halothane. Children are relatively spared.
Sevoflurane can react with carbon dioxide in the absorber and form Compound A, a nephrotoxin in animals, and 5% is metabolized to a fluoride. Also, isoflurane and desflurane can interact with carbon dioxide to form carbon monoxide. Toxicity has not been observed in anesthesia patients from neither of these sources.
Continue
to "Local Anesthesia" or take a quiz:
[Q1].
Need more practice? Answer the review questions below.
Questions coming soon