General Anesthetics Flashcards
General anesthesia as a condition includes what?
- Analgesia
- Anmnesia
- Loss of consciousness
- Also a loss of sensory and autonomic reflexes and general skeletal muscle relaxation
Most modern inhalational general anesthetics are based on what molecule that entered surgical anesthesia use in 1956?
• Halothane
Is the mechanism of action for inhaled general anesthetics easy to track?
• Nope. They have no single receptor
• Uncharged, nonpolar molecules with structures seemingly unrelated to one another
• Also, no specific antagonists of volatile anesthetics are known
○ Anticonvulsants and proconvulsants can decrease the duration of anesthesia
• CONTRAST - the IV general anesthetics are much better characterized
What are the important inhalational general anesthetics to know?
• Inorganic gases ○ Xenon, Nitrous oxide, nitrogen • Ethers ○ Diethyl ether • Hydrocarbons ○ Cyclopropane, ethylene • Chlorinated hydrocarbons ○ Chloroform, trichloroethylene • Fluorinated hydrocarbon ○ halothane • Fluorinated ethers ○ Enflurane, isoflurane, desflurane, sevoflurane
What are the IV general anesthetics that are important to know?
• Barbiturates ○ Thiopental • Benzodiazepines ○ Diazepam • Opioid analgesics ○ Morphine, fentanyl • Glutamate receptor agent ○ ketamine • Miscellaneous agents ○ Propofol, etomidate
What is the lipid theory of general volatile anesthetic mechanism of action?
• Behave as ideal gases thus their solubility in different media can be described by partition coefficients
○ Oil:water or Blood:gas
• The higher the oil:water partition coefficient, the more potent the general anesthetic
• Thus, evidence that they interact with lipids
• Also, MAC (minimum alveolar concentration to produce analgesia) is correlated with lipid solubility
What is the protein theory of general anesthetic mechanism of action?
- Instead of the lipid solubility truly meaning the gases mess with the neurons themselves, this theory suggests that the gasses actually mess with the proteins on the neuronal membrane
- The hydrophobic pockets of the proteins take up the anesthetic gasses, messing essentially with neuronal receptors and NT systems
- Evidence comes from in vitro experiemnts where anesthetic gases mess with protein properties without lipid bilayer
- Other evidence is the size cut-off for efficacy of these drugs, suggesting only certain sizes fit into the hydrphobic pockets of the membrane proteins
ESR evidence supports the protein theory over the lipid theory. What is ESR?
- Electron spin resonance
* Shows halothane trapped in protein, not lipid bilayer
Which neurons in the CNS are affected by general anesthetics?
- GABA systems. They are all CNS depressants
* Potentiation of GABA-a receptor activity by volatile and IV anesthetics
Though there are many documented mechanisms of action for general anesthetics, what is NOT believed to happen?
- Full conduction block
- Conduction block happens at concentrations above that used in clinical use
- Also, peripheral AP conduction is fine in anesthetized patients
What brain regions seem to be very sensitive to general anesthetics?
• Hypothalamic nuclei that produce sleep are probably the most sensitive
• Reticular formation of the brainstem b/c this is involved in control of pain sensation, alertness and sleep
○ Also, damage to this region can cause unconsciousness
• Hippocampus is also implicated b/c of amnesia
What is meant by “progression” in General Anesthetic Action
• It works by descending depression (progressive loss of function from higher (cognition) to lower (respiratory control) within the CNS
• Nobody knows why but the dose-dependence is from cognition and memory low to respiratory depression high doses
• List of progression
○ Fine motor and coordination
○ Alteration of consciousness and analgesia
○ Temp regulation
○ Consciousness
○ Eye motion, pupil size and light reflex
○ Loss of muscle tone
○ Respiratory failure
○ Cardiovascular failure
○ Coma and death
What are the 4 planes of surgical anesthesia?
• These are all in stage III of general anesthesia progression
• 1 - Regular metronomic respirations
• 2 - onset of muscular relaxation, fixed pupils
• 3 - good muscular relaxation, depressed excursion of intercostal muscles during
• 4 - diaphragmatic breathing only, dilated pupils
Why do you not want to overdose patients into stage IV of general anesthesia?
• Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes
What are the three periods of the time course of surgical anesthesia
• Induction
○ Time between initiation of admin and attainment of surgical anesthesia, until stage III is reached
• Maintenance
○ Time during which surgical anesthesia is in effect (surgery carried out during this period)
• Recovery
○ Time following termination of administration of anesthetic until complete recovery of patient from anesthesia
The volatile anesthetics behave like noble gases. What does this mean for determining concentration?
• The total pressure exerted by a mixture of non-reacting gases is equal to the sum of the partial pressures of the individual gases
○ Dalton’s law
• The amount of a gas dissolved in a liquid solution is proportional to the partial pressure of the gas to which the solution is exposed
○ Henry’s law
