General Anesthetics Flashcards
Unifying thing of ana
GABA A
General anesthetics prefer an _________environment
oily
General anesthetics act
central
topical acts local
Anesthetic potency correlates with
oil:gas partition coefficient
MAC = Minimum
Potency ~ 1/MAC
Alveolar Concentration of a GA that produces insensibility to pain in 50% of subjects
GAs and luciferase: protein theory of GA action
Firefly luciferase is a globular protein found in the cytoplasm, not cell membrane. But GAs inhibit luciferase light emission …
GA can work in absence of oily membrane
Cl channel INSIDE memorable is hydrophobic- Proteins have OILY cores
We believe GA WORKS here- in the oily core
It does like to hang out in membrane though
Other evidence in favor of a GA “receptor site”
• Size cut-off: for a series of structurally-related compounds that differ only in size,
only compounds below a certain size cut-off have anesthetic effects. This can be
explained by assuming that anesthetic molecules must fit into pockets of specific
size within membrane proteins, such as ion channels.
• Electron spin resonance (ESR) measurements show that volatile anesthetic is immobilized in nerve membrane, as though it binds to immobilized membrane
proteins rather than being freely diffusible. In contrast, volatile anesthetic in pure
lipid bilayers is not immobilized.
• ESR also shows that volatile anesthetic solvation in pure lipid bilayers is not
saturable, but that volatile anesthetic solvation in (protein-containing) membranes
exhibits a saturable component. This suggests that nerve cell membranes contain
a finite number of sites with which volatile anesthetics interact.
• Stereoselectivity: 1 of the 2 optical isomers of isoflurane is a more potent anesthetic than the other isomer, and a more potent inhibitor of GABAA receptors.–This is suggestive of a structured site or pocket in proteins such as ion channels.
Size cut-off: for a series of structurally-related compounds that differ only in size,
only compounds below a certain size cut-off have anesthetic effects. This can be
explained by assuming that ____________
anesthetic molecules must fit into pockets of specific size within membrane proteins, such as ion channels.
ESR also shows that volatile anesthetic solvation in pure lipid bilayers is not
saturable, but that ___________________. This suggests that nerve cell membranes contain
a finite number of sites with which volatile anesthetics interact.
volatile anesthetic solvation in (protein-containing) membranes
exhibits a saturable component.
___________ 1 of the 2 optical isomers of isoflurane is a more potent anesthetic than the other isomer, and a more potent inhibitor of GABAA receptors.
This is suggestive of a structured site or pocket in proteins such as ion channels.
Stereoselectivity
Other ion channels affected by clinically relevant levels of GA include:
Potentiation of glycine receptors (↑inhibitory transmission)
• Inhibition of brain nicotinic acetylcholine receptors (↓excitatory
transmission)
• Potentiation of TASK-1 K+ channels that set resting potential (↓ excitability)
Actions of GAs that occur only above the clinical range:
Impaired conduction of action potentials: occurs at concentrations above
clinical range, so conduction block does not underlie anesthesia.
Conduction in peripheral nervous system is normal in anesthetized patients.
• Inhalational anesthetics act on voltage-gated Na+, Ca2+ and K+ channels , but
only at anesthetic levels substantially higher than that needed to induce surgical anesthesia.
Inhalational anesthetics act on voltage-gated Na+, Ca2+ and K+ channels , but
__________
only at anesthetic levels substantially higher than that needed to induce
surgical anesthesia
Impaired conduction of action potentials: occurs at concentrations above
clinical range, so ____________
Conduction in peripheral nervous system is normal in anesthetized patients.
conduction block does not underlie anesthesia.
Recent evidence suggests that _________ are particularly sensitive to general anesthetics.
hypothalamic nuclei involved in sleep
Another suspected region is the_____________, because this is involved in control of pain sensation, alertness and sleep and because damage to
this region can cause unconsciousness.
reticular formation of the brainstem
The amnesia of postoperative patients (inability to recall events that occur during
surgery) is suggestive of a role for the ____________, since this brain structure is involved in short term memory.
hippocampus
Be alert to signs of respiratory failure because the patient can be _____________
Respiratory failure occurs prior to circulatory failure, so volatile general anesthetics
can be removed via artificial respiration, provided that circulation remains functional.
resuscitated following accidental overdose of volatile anesthetic, if circulation is preserved.
Guedel’s Stages & Planes of anesthesia
- Stage I – analgesia
- Stage II – excitement, delirium
• Stage III – surgical anesthesia (cannot be reached with N2O)
Plane 1 regular, metronomic respirations
Plane 2 onset of muscular relaxation, fixed pupils
Plane 3 good muscular relaxation, depressed intercostal muscle function
Plane 4 diaphragmatic breathing only, dilated pupils
• Stage IV – medullary paralysis: respiratory failure, vasomotor collapse and resulting
circulatory failure lead to death within minutes.
Volatile GA occupancy of hydrophobic pockets in membrane proteins alters the
function of these proteins, _____________ and
producing general anesthesia.
depressing central nervous system function
Volatile anesthetics and intravenous anesthetics potentiate_____________, and this effect seems to be key in anesthesia.
GABAergic IPSPs in the
CNS
Because these pockets are not specific binding sites, volatile anesthetics exert
clinically-relevant effects only at concentrations much higher_____than
those needed for drugs with specific binding sites.
(∼1-100 mM)
The hydrophobic protein pockets within which volatile anesthetics bind are not
_______, but pocket size does account for the size cut-off for volatile
anesthetics.
specific binding sites
Volatile GAs
(i) partition into the membrane, and
(ii) enter hydrophobic pockets in
various membrane proteins such as GABAA receptors, other ion channels and perhaps proteins involved in neurotransmitter release.
