Egar Video #4 Mechanisms of Inhaled Anesthetic Actions

Question 1

Knowing the MOA of inhaled anesthetics implies that ________

Answer 1

we know what anesthesia is

Question 2

what is the anesthetic state?

Answer 2

• patient doesn’t remember or doesn’t move.
• consciousness and pain would be irrelevant if they don’t remember

Question 3

What are the autonomic response to pain in patients under inhaled anesthetics with no analgesia?

Answer 3

elevated HR and BP
might have to give opiods
inhaled anesthetics are not very good analgesics

Question 4

Anesthesia (at least for an inhaled anesthetic) is a _____ ______ mediated by the central nervous system that produces…..

Answer 4

Reversible State
Produces: immobility during noxious stimuli and amnesia-unawareness

All other states are side effects

Question 5

______ recognized the immobility produced by anesthetics

Answer 5

John Snow (first great anesthetist)
- “Ether contributes other benefits besides preventing pain … it keeps patients still…”

Question 6

_____ is the inability to remember events during anesthesia

Answer 6

Amnesia
produced by ALL inhaled anesthetics

Question 7

If a patient cannot move during anesthesia and cannot remember, then _____ during anesthesia cannot be assessed; it is ______

Answer 7

unconsciousness; irrelevant

Question 8

surgical stimulation _____ ventilation at all anesthetic concentrations

Answer 8

increases

Question 9

Not all anesthetics produce _____

Answer 9

Relaxation

Question 10

______ inhaled anesthetics cause profound relaxation

Answer 10

potent

Question 11

Anesthesia with _____ (in a hyperbaric chamber) increases ____ _____

Answer 11

nitrous oxide; muscle tone

Question 12

Nitrous Oxide can increase muscle tone at ____ atm or when given with ____

Answer 12

1.55; opiods

Question 13

Where do anesthetics work?

Answer 13

the spinal cord

Question 14

What is the Meyer–Overton hypothesis?

Answer 14

Anesthetic potency was directly related to its lipophilicity
more liphophilic: more potent –> vice versa

Question 15

Meyer-Overton Hypothesis Equation

Answer 15

MAC (atm) multiplied by Oil/Gas partition coefficient = a constant

Constant in rats = approx 1.8 atms

Question 16

increasing the _____ decreases the MAC

Answer 16

Oil-Gas paritition coefficient

Question 17

Meyer-Overton Constant’s affinity to ____ doesn’t change

Answer 17

water
Meyer-Overton’s Constant doesn’t change with increasing saline/gas partition coefficient

Question 18

If anesthetic potency is correlated with lipophilicity, where are the anesthetics acting?

Answer 18

on the lipophilic sights of the lipid bilayer

Question 19

Compounds that Disobey the Meyer-Overton Hypothesis

Answer 19

• Alkanols: more potent than lipophilicity predicts
• transitional compounds: less potent than lipophilicity predicts
• Nonimmobilizers: no anesthetic potency

Question 20

What distinguishes Alkanols, transitional compounds and nonimmobilizers?

Answer 20

• their affinity for water
• In conventional anesthetics, their affinity to water didn’t change
• But looking at a broader range (7 orders of magnitude), there is an effect for affinity to water.
• GREATER the affinity to water, LOWER the meyer- overton constant

Question 21

Where do these compounds work on the membrane?

Answer 21

Both on the hydrophilic and lipophilic sights (head and tail of the lipid bilayer)

Question 22

Anesthetics that work on lipo and hydro philic sights are called?

Answer 22

Amphepathics

Question 23

Types of interphases where hydrophilic anesthetics works

Answer 23

Lipid bilayer-aqueous interface
Protein-Aqueous interface
Aqeous pocket within protein
Ion channel/ionophores

Question 24

Anesthesia could result from ______ of inhibitory ionophores or _____ of excitatory ionophores

Answer 24

enhancement; depression

Question 25

Ionophores that might mediate (plausible mediators) inhaled anesthetic actions

Answer 25

GABA-A
Glycine
Potassium
Glutamate
Acetylcholine
Serotonin
Nitric Oxide
Calcium
Sodium

Question 26

Does plausible mean relevent?

Answer 26

No, just because it works on a receptor, that doesn’t mean it contributes to the anesthetic effect

Question 27

Example of plausible targets

Answer 27

Here is the effect of anesthesia on the current produced by Acetylcholine application to neuronal acetylcholine receptors.
The concentrations are within the anesthetic range. They show a great sensitivity to the acetylcholine receptor. In the picture, we get blockade of the Ach receptor around MAC 1 with sevo, halo and iso. This is a plausible target.

Question 28

Blockade of muscurinic and/or nicotinic Ach receptors does NOT change _____

Plausible does not mean _____

Answer 28

MAC; relevant
No matter how high the dose, the MAC still doesn’t change.

Question 29

5 Carbon Hypothesis

Answer 29

An experiment was done that suggests the 5 carbon hypothesis:
- they took compounds that had hydrogens on either end and added CF2 groups in between
- as you add, you increase the potency of the compound
- in the graph: the alkane MAC’s potency increased up to 4 carbons. Past 4 carbons, potency is lost
- Alkanol: hydrogen group on one end and alcohol group on the other, we lose potency beyond 5 carbons

Question 30

_____ is a nonimmobilizer

Answer 30

Hexane

Question 31

you can increase the potency of an anesthetic to a maximum of ______

Answer 31

4-5 carbons
5 carbon hypothesis

Question 32

Inhaled anesthetics act on the _____ to produce ______

Answer 32

spinal cord; immobility

Question 33

A modified Meyer-Overton hypothesis suggests that anesthetic target sites have both ____ and ______ components

Answer 33

polar and nonpolar

potency is a function or lipophilicity and hydrophilicity
anesthetics are amphepathic and must be to cause anesthesia

Question 34

Various receptors form _____ targets but only 1 or 2 are likely to be ______

Answer 34

plausible; relevant

these don’t include GABA-A, ACh or serotonin receptors

Question 35

specific sites within receptors have been suggested as _____.
Perhaps 2 sites and _______/angstroms apart that are important to the action of inhaled anesthetics

Answer 35

sites; 5 carbons

Ex: the 270th amino acid in the glycine receptor has been suggested as a specific anesthetic target

Question 36

Amnesia sight is in the ____ and not the ____

Answer 36

brain; spinal cord

Question 37

nonimmobilizers produce _____ but they do not produce immobility

Answer 37

amnesia

Question 38

Nonimmobilizers can impair memory

Answer 38

• test was done where animals were kept in an electrical chamber.
• And when a shock was delivered a light was produced with it and the animal jumps.
• The animal learns to associate the light with the shock.
• You later swap the shock with a tone, and the animal jumps at the tone.
• You measure the acceleration of the jump
• this could be done with the animal breahting oxygen, anesthetic or nonimmobilizer

Graph conclusion: the jumps are suppressed with a concentration range that is the same as the suppression you see with desflurane

Question 39

For all the anesthetic compounds, amnesia is achieved when ____ is achieved

Answer 39

immobility

Question 40

T/F: nonimmobilizers are compounds that possess hydrophilicity

Answer 40

false, so they act on the lipophilic portion of the membrane and not the surface