Mechanism of Action of Sevoflurane
Sevoflurane works primarily by enhancing inhibitory neurotransmission and depressing excitatory neurotransmission in the central nervous system through multiple molecular targets, with its low blood:gas solubility (0.63-0.69) enabling rapid induction and emergence from anesthesia.
Primary Mechanisms of Action
Sevoflurane, an ether inhalational anesthetic agent, exerts its effects through several mechanisms:
Neurotransmitter Receptor Modulation
- GABA Receptors: Potentiates inhibitory GABA-mediated neurotransmission
- Glycine Receptors: Potently enhances glycine receptor currents 1
- NMDA Receptors: Modestly antagonizes NMDA receptors, contributing to immobility 1
Molecular Targets
- Ion Channels: Affects multiple ion channels including potassium channels
- Mitochondrial Function: Decreases mitochondrial membrane potential in a dose-dependent manner 2
- Intracellular Signaling: Activates specific intracellular signal transduction pathways that contribute to cardioprotective effects 2
Pharmacokinetic Properties
Sevoflurane's clinical profile is largely determined by its pharmacokinetic properties:
- Low Blood:Gas Partition Coefficient: 0.63-0.69 3
- Rapid Uptake and Distribution: Faster than isoflurane and halothane but slower than desflurane 3
- Metabolism: Approximately 5% metabolized by cytochrome P450 2E1 to hexafluoroisopropanol (HFIP), which is rapidly conjugated with glucuronic acid and eliminated in urine 3
Clinical Implications of Pharmacokinetics
- Rapid Induction: The low solubility means minimal sevoflurane needs to dissolve in blood before alveolar partial pressure equilibrates with arterial partial pressure 3
- Precise Control: Facilitates precise control over anesthesia depth 4
- Quick Recovery: Low blood solubility enables rapid elimination via the lungs 3, 5
Physiological Effects
Cardiovascular System
- Myocardial Depression: Causes dose-dependent depression of myocardial contractility 2
- Afterload Reduction: Decreases systemic vascular resistance 2
- Cardioprotection: Preconditions and postconditions the heart against infarction by activating specific intracellular pathways 2
Respiratory System
- Non-irritating: Unlike some other volatile anesthetics, sevoflurane has minimal airway irritant effects 5, 6
- Respiratory Depression: Produces dose-dependent respiratory depression 5
Central Nervous System
- Dose-dependent CNS Depression: Produces general anesthesia through progressive depression of CNS function 5
- Cerebral Blood Flow: Minimal effect on cerebral blood flow compared to other agents 7
Clinical Advantages
- Smooth Induction: Non-pungent odor and lack of airway irritation make it ideal for mask induction in both adults and children 5, 4
- Rapid Recovery: Quick emergence from anesthesia due to low blood solubility 5, 4
- Hemodynamic Stability: More favorable cardiovascular profile than some other inhalational agents 4
Important Considerations
Potential Interactions
- Drug Displacement: Effects on displacement of drugs from serum and tissue proteins have not been fully investigated 3
- Metabolic Interactions: Metabolism is not inducible by barbiturates 3
Unique Molecular Effects
- Immune Modulation: Affects immune function through multiple pathways including:
In summary, sevoflurane's mechanism of action involves multiple targets in the CNS with its clinical utility enhanced by favorable pharmacokinetic properties that allow rapid induction and emergence from anesthesia.