VPT 321: Veterinary Neuropharmacology (2+1)

INHALANT ANAESTHETICS

• Inhalation anaesthetics are classified as gases and volatile liquids.
•  Based on their use, they are also calssified as follows.
  • Group I Agents in current clinical use
    • Major use – Halothane, Isoflurane
    • Minor use – Enflurane, methoxyflurane, nitrous oxide, ether
  • Group II New agents – Desflurane, sevoflurane
  • Group III Agents of historical interest
    • Chloroform, cyclopropane, fluroxene, trichloroethylene

Properties influencing drug kinetics

• Solubility – The solubility of an inhalation anaesthetic in blood and tissues is characterised by its partition coefficient. An anaesthetic agent with a low blood/gas partition coefficient is usually more desirable than a soluble agent because it is associated with (i) a more rapid anaesthetic induction, (ii) more precise control of anaesthetic depth (iii) more rapid elimination of anaesthetic and recovery from anaesthesia.
• Blood/gas partition coefficient: This is a measure of the speed of anaesthetic induction, recovery and change of anaesthetic levels.
• Oil/gas partition coefficient: This describes the ratio of concentration of an anaesthetic in oil and gas phases at equilibrium. The oil/gas partition coefficient correlates inversely with anaesthetic potency and describes the capacity of lipids for anaesthetics.
• Pharmacokinetics
• Uptake and elimination of inhalation anaesthetics - The aim of administering an inhalation anaesthetic to a patient is to achieve an adequate partial pressure or tension of anaesthetic in the brain, to cause a desired level of anaesthesia. Gases move from regions of higher tension to those of lower tension, until equilibrium is established.
• Delivery to the alveoli – This depends on the inspired anaesthetic concentration and the magnitude of alveolar ventilation.
• Inspired concentration – The upper limit of inspired concentration is directed by the vapour pressure of the agent that in turn is dependent on the temperature.
• Alveolar ventilation - An increase in alveolar ventilation increases the rate of delivery of inhalation anaesthetics to the alveoli. Alveolar ventilation is altered by changes in anaesthetic depth, mechanical ventilation or changes in dead space ventilation.
• Removal from alveoli – This is dependent upon the uptake by blood.
• Uptake by blood – Anaesthetic uptake is the product of three factors namely (a) solubility, (b) cardiac output and (c) the differences in anaesthetic partial pressure between the alveoli and venous blood returning to the lungs.
• Cardiac output – The greater the cardiac output, the more blood passing through the lungs carrying away the anaesthetic from the alveoli.
• Alveolar to venous anaesthetic partial pressure: The magnitude of difference in anaesthetic partial pressure between the alveoli and the venous blood is related to the amount of uptake of anaesthetic agent by tissues. The largest gradient occurs during induction.
• Anaesthetic recovery – Recovery from inhalation anaesthesia results from the elimination of anaesthetic from the brain. A factor that is important in the rate of recovery but not during the induction period is the duration of anaesthesia. Other factors that are important to varying but smaller degree to inhalation anaesthetic elimination from the body include percutaneous loss and inter tissue diffusion of agents.
• Biotransformation – Inhalation anaesthetics are not chemically inert. They undergo varying degree of metabolism primarily in the liver, but to a lower degree in the lung, kidney and intestinal tract.
• Anaesthetic dose - MAC (minimal alveolar concentration) – It is the lowest concentration of the anaesthetic in pulmonary alveoli needed to produce immobility in response to painful stimulus in 50% of individuals. The MAC of a number of general anaesthetics exhibits excellent correlations with their oil/gas partition coefficient.
• The anaesthetic potency of an inhaled anaesthetic is inversely related to MAC. Thus, a very potent anaesthetic has a low MAC value and a high oil/gas partition coefficient.