Lect 14

• Dissociative and Inhalant Anesthetics are drugs that act on the Central Nervous System (CNS).
• Inhalant Anesthetics are pharmacologically and physically different from injectable anesthetics.
• Ketamine, a dissociative anesthetic, has a unique mechanism of action that involves interrupting the connection between the cortex and the limbic system, stimulating opioid receptors for sedation and analgesia, and stimulating catecholamine release for increased cardiac output and bronchodilation.
• Telazol R, a dissociative anesthetic, has a mechanism of action that involves blocking the N-methyl-D-aspartate receptors (NMDARs), ion channels mainly involved in excitatory Glutamatergic Neurotransmission.
• Isoflurane maintains cerebral blood flow, maintains cardiac output, heart rate, and rhythm with fewest adverse effects, is almost completely eliminated through the lungs (89%), and has other effects such as inducing adequate to good muscle relaxation and providing little or no analgesia after anesthesia.
• Methoxyflurane is no longer available in North America.
• Nitrous oxide is used primarily in human medicine, but some veterinarians use a gas at room temperature, no vaporizer is required.
• Doxapram is a specific respiratory stimulant used for shortening recovery following inhalation anesthesia.
• Sevoflurane is stable at room temperature, does not require preservatives, has a low blood:gas partition coefficient for rapid induction and recovery, and is more expensive than Isoflurane.
• Sevoflurane provides high controllability of depth of anesthesia, but is more expensive and has a higher anesthetic index in dogs than Isoflurane.
• Halothane, not commonly used anymore, is being replaced by Isoflurane and Sevoflurane.
• Desflurane has similar properties to Isoflurane, is used with a special precision vaporizer, has the lowest blood:gas partition coefficient, is good for induction with mask or chamber, and has a MAC of 7.2% to 9.8%, making it the least potent inhalant agent.
• Ketamine is metabolized in the liver.
• Ketamine affects many other targets: dopaminergic, serotonergic, adrenergic, opioidergic, cholinergic as well as acts on serotonin, norepinephrin, and dopamine reuptake transporters and various other ion channels.
• Ketamine, the classical NMDAR antagonist, is a non-competitive inhibitor of NMDA receptors.
• Ketamine has low binding to plasma proteins (12-47% binding).
• Ketamine is excreted by the kidney (detected in urine).
• Ketamine is water soluble, stable and non-irritant when administered IV.
• Ketamine's lipid-solubility is 5 times higher than thiopental.
• Ketamine is used alone in cats for minor procedures or to facilitate restraint.
• Ketamine has extensive distribution and rapid onset.
• Ketamine is used with other drugs, such as tranquilizers and opioids, to induce general anesthesia.
• Ketamine affects NMDA-Receptors on GABA interneurons eventually resulting in high GABA and low Glutamate levels.
• Ketamine has rapid onset and provides anesthesia in continuous infusion.
• A sub-anesthetic dose of Ketamine is administered as a constant-rate infusion (CRI) for analgesia.
• Ketamine is a classical NMDA receptor antagonist.
• Vapor Pressure (VP) is an indicator for IAs' ability to evaporate.
• VP is temperature- and anesthetic-dependent.
• MAC may be altered by age, body T, metabolic activity, obesity, pregnancy, disease state and other agents present.
• The tendency of an IA in the liquid state to enter the gaseous (vapor) state determines how readily an IA will evaporate in the vaporizer.
• High vapor pressure IAs evaporate more easily, have a blood:gas partition coefficient of less than 0.1, and are delivered from a precision vaporizer.
• Volatile agents have a high vapor pressure and are delivered from a precision vaporizer to control the delivery concentration.
• Isoflurane and Sevoflurane are the most commonly used inhalant agents in North America.
• Adverse effects of IAs include dose-related reversible CNS depression, hypothermia, and are safe for epileptic animals.
• Properties of IAs include high vapor pressure, good for induction with mask or chamber, and low rubber solubility.
• Inhalant Anesthetics (IAs) include Halogenated Compounds, Diethyl Ether, Nitrous oxide (N 2 O), Chloroform, Halothane, Xenon gas, Enflurane, Isoflurane, Desflurane, Sevoflurane.
• Low vapor pressure IAs are less soluble in blood, have a blood:gas partition coefficient of greater than 0.1, and are delivered from a non-precision vaporizer.
• Blood:Gas Partition Coefficient (B:G PC) is the measure of the solubility of an IA in blood as compared to alveolar gas (air).
• The exact mechanism of action for IAs remains mostly unknown, but fundamentally, IAs work within CNS by inhibiting signals through GABA receptors, NMDA receptors, M and N receptors, and serotonin receptors.
• Minimum Alveolar Concentration (MAC) is the measure of the potency of a drug used to determine the average setting on the vaporizer that will produce surgical anesthesia.