Inhalation Anesthetics and Pharmacokinetics

Inhalation Anesthetics

• Nitrous oxide and halogenated anesthetics (Halothane, Isoflurane, Sevoflurane, Enflurane) are types of inhalation anesthetics.
• They interact with protein receptors to produce anesthetic effects.

Mechanism of Action

• Volatile anesthetics increase the activity of inhibitory neurotransmitters GABA and Glycine.

Pharmacokinetics of Inhaled Anesthetics

• The amount of anesthetic that reaches the brain is indicated by the oil:gas ratio (lipid solubility).
• The lower the blood:gas ratio, the more anesthetic will reach the brain.

General Actions of Inhaled Anesthetics

• Respiratory system: Depressed respiration and response to CO2.
• Kidney: Depression of renal blood flow and urine output.
• Muscle: High enough concentrations will relax skeletal muscle.
• Cardiovascular system: Generalized reduction in arterial pressure and peripheral vascular resistance.

Complications of Inhaled Anesthetics

• Regurgitation: Patient should be placed in the Trendelenburg position and material aspirated with suction apparatus.
• Intraarterial injection of thiopentone: Causes pain and blanching in hand and fingers due to crystal formation in capillaries.
• Prevenous injection: Causes blanching and pain, and may result in a small degree of tissue necrosis.
• Cardiovascular depression: More likely to occur in elderly, hypovolemic, or untreated hypertensive patients.
• Respiratory depression: Slow injection of an induction agent may reduce the extent of respiratory depression.
• Histamine release: Thiopentone may cause release of histamine with subsequent formation of typical weal.

Intravenous Induction Agents

• Commonly used IV induction agents: Propofol, Thiopental sodium, Ketamine.

Intravenous Anesthetics

• Most exert their actions by potentiating GABAA receptor.
• GABAergic actions may be similar to those of volatile anesthetics, but act at different sites on the receptor.

Organ Effects of IV Anesthetics

• Most decrease cerebral metabolism and intracranial pressure.
• Most cause respiratory depression.
• May cause apnea after induction of anesthesia.
• Cardiovascular effects: Barbiturates, benzodiazepines, and propofol cause cardiovascular depression.

Thiopental Sodium

• Rapid onset (20 seconds) and short-acting.
• Effect is terminated not by metabolism but by redistribution.
• Repeated administration or prolonged infusion approaches equilibrium at redistribution sites.
• Build-up in adipose tissue leads to very long emergence from anesthesia.
• Side effects: Hypotension, apnea, airway obstruction.

Propofol

• Short-acting agent used for induction and maintenance of general anesthesia and sedation.
• Onset within one minute of injection.
• Highly protein-bound in vivo and metabolized by conjugation in the liver.
• Side effects: Pain on injection, hypotension, transient apnea following induction.

Ketamine

• NMDA receptor antagonist.
• Usually stimulates rather than depresses the circulatory system.