General Information
Mechanism of Action of General Anesthetics
• They block ion channels (especially sodium channels) by changing the lipid matrix of the neuron membrane.
• They form GA by increasing GABA-A receptor activity. General anesthetics that do this; inhalation anesthetics, barbiturates, benzodiazepines, etomidate, propofol
• Ketamine, nitrous oxide (N2O), cyclopropane and xenon act by inhibiting the NMDA receptors of glutamate.
Termination of Effect of General Anesthetics
• Removal from the brain by redistribution; It is the most important factor in terminating the effects of anesthetic agents.
Excretion and Metabolism
• Intravenous general anesthetics are metabolized in the liver and excreted from the body.
• Halogenated inhalation anesthetics are metabolized in the liver to varying degrees.
• There is a relationship between the degree of metabolism of these drugs and the degree of toxicity. Methoxyflurane and halothane are the most soluble in the blood and therefore the most metabolized general anesthetics, respectively.
• With their metabolism, fluorine begins to be released and the resulting fluorine is also toxic to the kidney. Methoxyflurane, a halogenated ether derivative, is the general anesthetic that causes the most fluorine release. As a result of halothane metabolism, hepatotoxic trifluoroacetic acid and bromine are formed. Nitric oxide, xenon, isoflurane, desflurane and sevoflurane are metabolized very little.
Parameters Determining the Rate of Entry into Anesthesia
• Blood Solubility
• Minimum Alveolar Concentration (Max)
• Alveolar Blood Flow
• Respiratory Rate: The higher it is, the faster the introduction to anesthesia.
• Partial Pressure Difference Between Arterial-Venous Blood: The higher it is, the faster the introduction to anesthesia.
• Density of Anesthetic Gas Mixture: Anesthesia develops faster with low-density substances.
Minimum alveolar concentration (MAK)·
• It is the concentration of alveolar anesthetic at atmospheric pressure that causes unresponsiveness to painful stimuli in 50% of people.
• This value gives the POTENS of general anesthetics.
• The smaller the potency value, the stronger the drug.
• The lower the MAC value, the stronger the drug is. The strongest general anesthetic is methoxyflurane, and the weakest general anesthetic is nitrous oxide.
Their solubility in blood (blood gas partition coefficient)
• The less a general anesthetic dissolves in the blood, the faster the introduction to anesthesia. The opposite is also true. In other words, the more a general anesthetic dissolves in the blood, the later is the introduction to anesthesia.
• The same rules apply for the recovery phase from anesthesia. In other words, the less soluble a general anesthetic is in the blood, the faster the recovery from anesthesia. The more it dissolves, the slower the recovery from anesthesia
Minimum Alveolar Concentration (MAC) of Inhalation Anesthetics Factors
Increases MAC: chronic ethanol use
Hyperthermia
Hypernatremia
Monoamine oxidase inhibitors
Acute dextroamphetamine administration
cocaine
Ephecrine
Levodopa
Those that decrease MAC: Increasing age
Barbiturates
Benzodiazepines, opioids
Ketamine/Verapamil/Lithium
Acute ethanol intoxication
Clonidine and dexmedetomidine
Hypothermia/hyponatremia
pregnancy
The strongest general anesthetic is methoxyflurane, the weakest general anesthetic is nitrous oxide.
