Anesthetics I and II Flashcards
How might Anesthetics interfere w/CNS function?
most likely by reducing communication between neurons (inhibiting excitatory neurons like glutamate, enhancing inhibitory neurons like GABA)
*though volatile anesthetics have also been shown to decrease GABA release too
Which Voltage gated ion channels to anesthetics work on?
Na channels – they inhibit activity at the channel to cause a reduction in NT release at some synapses
What are the 3 receptor types located on ion channels that Glutamate acts on? Which of these are nonselective?
AMPA, Kainate and NMDA.
Kainate and AMPA are non-selective
How to drugs act on NMDA receptors?
NMDA modulate long term synaptic responses (through Na, K and Ca); volatile anesthetics, ketamine and N20 may inhibit NMDA receptors
What are the 3 types of effects that drugs produce on the GABA-A receptor?
1) Potentiation (increased Cl- produced by low [GABA] but no increase if GABA maximally effective
2) Direct gating (activating GABA receptor in absence of GABA through high [drug])
3) Inhibition (preventing GABA from initiating Cl- current at high concentration of anesthetics)
What is the Meyer Overton Rule and the Unitary Theory of Anesthesia?
Meyer Overton says “potency of anesthetic gases directly related to solubility in olive oil”
Unitary Theory says “since variety of structurally unrelated drugs “obey” the rule, they must bind at same hydrophobic site
So, where to anesthetics bind – lipids or protein?
Hydrophobic pockets on proteins
Of the inhaled anesthetics, which are inorganic gases and which are volatile liquids?
Inorganic gas: N2O
Volatile liquids: Halothane, Enflurane, Isoflurane, Desflurane, Sevoflurane
Which of the inhaled anesthetics boils at a much lower temperature and as such has a much higher vapor pressure?
Desflurane (bp = 22.8 around room temp and vapor pressure 669 mmhg)
How does the anesthesia machine deliver isoflurane and sevoflurane? How is desflurane different?
oxygen or oxygen/N2O mixture passes over surface saturated w/the volatile anesthetic and mixes with it; then it’s delivered to lungs.
desflurane boils and goes through a “dual gas blender” where it is added directly to the main gas stream
How are inhaled anesthetics taken up into the body, distributed and eliminated?
Uptake: absorbed from alveoli into pulmonary capillary blood
Distribution: to site of action (brain) and “reservoirs” (vessel rich group, muscle, fat)
Eliminated: by lungs mostly
What is Henry’s Law (partial pressures rule!!)
Concentration of a gas is directly proportional to the partial pressure of the gas above the solution
What is the partition coefficient?
Ratio of solubilities of a gas between 2 compartments (blood:gas, brain:blood) at equilibrium; describes how anesthetics distribute themselves between different tissues at equilibrium
WHat’s the deal w/equilibration, partial pressure and concentration?
Equilibration means that the same PARTIAL PRESSURE of an anesthetic gas exists in both phases; NOT that the same concentration exists in both phases
What does alveolar partial pressure equilibrate with?
pulmonary capillary blood partial pressure and brain partial pressure. Goal = constant brain partial pressure of inhaled gas
What determines alveolar partial pressure?
delivery of anesthetic to alveoli MINUS uptake of anesthetic to blood
How do you ensure enough gas is administered into the patient’s lungs?
increase inhaled partial pressure of the gas above what is needed to produce anesthesia (over-pressurization)
What is the 2nd gas effect?
ability of high volume uptake of one gas (N2O) to accelerate rate of increase of alveolar pp of a second gas (ie O2 and anesthetic)
What is the speed of anesthetic induction determined by?
rate of rise of alveolar concentration of the anesthetic agent; POORLY SOLUBLE agents achieve HIGH ALVEOLAR concentrations and INDUCTION OCCURS MORE QUICKLY
What is the most soluble inhaled anesthetic? The least?
Most: Halothane
Least: N2O
What is the Minimum Alveolar Concentration (MAC)?
concentration of an inhaled anesthetic agent at which 50% of patients will NOT move in response to surgical incision; a common measure of potency; related to solubility in olive oil
Where is the site of action to produce immobility? At what MAC does loss of awareness and recall occur?
site of action = spinal cord (not brain!)
loss of awareness/recall at .4-.5 MAC
What are some factors that increase MAC? decrease MAC?
increase MAC: hyperthermia, pheomelanin (red hair), increased CNS catecholamines, cyclosporine, hypernatremia, increased central NTs
decrease MAC: hypothermia, age, decreased CNS catecholamines, opioids, hyponatremia, pregnancy and post partum period
Describe the inhaled anesthetics in terms of potency and solubility
N2O = relatively insoluble in blood
Isoflurane = most potent
Desflurane = least soluble, least potent
Sevoflurane, less soluble, less potent, nonirritant
Halothane and enflurane are available outside the US
What is important about N2O?
1) doesn’t produce muscle relaxation
2) associated with post op nausea/vomiting
3) inactivates vitamin B12
4) accumulates in closed, air-containg spaces
5) adverse effects on embryonic development
6) used for mask induction in children
What is important about Isoflurane?
1) Potent, somewhat pungent (thus mask induction difficult)
2) “Gold Standard” for maintenance of general anesthesia
What is important about Desflurane?
1) Differs from isoflurane by substitution of Fl for Cl
2) Complete fluorination of ether which decreases blood and tissue solubility (to allow for rapid emergence) and decreases potency
3) Most pungent of the volatile agents
4) Mask induction can cause: coughing, salivation, breath holding, laryngospasm
Sevoflurane
1) sweet smelling, non-pungent bronchodilator for kids and adults
2) more soluble than desflurane (less than isoflurane)
3) half as potent as isoflurane
4) can form CO when exposed to strong bases present in dry CO2 absorbers (canister fires!)
What are the physiological effects of volatile agents on the CNS?
depression of EEG, sensory/motor function, cerebral metabolic rate
increase in cerebral blood flow and increase in intracranial pressure
What are the physiological effects of volatile agents on cardiovascular function?
decrease in vascular resistance/BP, minimal effects on cardiac contractility (though isoflurane and desflurane incr heart rate by 5-10%), redistribution of blood flow (increase to brain, decrease to liver/kidneys/gut)
What are the physiological effects of volatile agents on respiratory function?
decrease in tidal volume, response to hypoxia and hypercarbia; increase in RR, relaxation of airway smooth muscles
What are the physiological effects of volatile agents on airway function?
directly relaxes skeletal muscle, potentiates the effects of neuromuscular blockers, triggers malignant hyperthermia in susceptible patients
What are all of the IV anesthetics we are responsible for knowing?
barbiturates (thiopental, methohexital), propofol, etomidate, phencyclidines (ketamine), a2 agonists (dexmedetomidine)
How do Barbiturates act as anesthetics?
rapid onset (short duration of action), provide ONLY hypnosis/sedation; used essentially to induce anesthesia
dose based on lean body mass
How do barbiturates produce hypnosis?
enhance GABA(A) receptor release of Cl (though can act as direct agonist at higher concentrations); inhibit excitatory NTs (ex:NMDA)
