General Anesthetics I & II

Question 1

Nitrous oxide has what chemical structure?

Answer 1

It is cyclic!

Question 2

More potent anesthetics are __________ soluble in oil.

Answer 2

more

Question 3

Which general anesthetics are more potent, nitrous oxide or halogenated compounds?

Answer 3

Halogenated compounds; in fact, nitrous oxide is only used in combination with other compounds

Question 4

It used to be thought that general anesthetics interacted with the lipid layer, but research on luciferase contradicted this. Describe!

Answer 4

General anesthetics inhibit luciferase, which is intracellular. This indicates that general anesthetic must pass into cells.

Question 5

What evidence suggests that general anesthetics must fit into a receptor pocket?

Answer 5

• Some compounds that are bigger but differ only in size (that is, they have similar chemical composition and properties) will not induce the anesthetic properties of smaller counterparts.
• Some anesthetics are fixed in membranes, whereas they would be freely diffusible if they just interacted with lipid membranes.
• General anesthetics are saturable, whereas they would not be if they were merely interacting with the lipid membrane.
• Only one enantiomer works, which would not be the case if volatile anesthetics only disrupted lipid membranes.

Question 6

Halothane does what to GABA?

Answer 6

It prolongs GABA current.

Question 7

At clinically relevant levels, what do general anesthetics do?

Answer 7

• Potentiate glycine channels
• Inhibition of acetylcholine receptors
• Potentiation of TASK-1 potassium channels

Question 8

What concentration is needed to achieve anesthesia?

Answer 8

~ 100 mM

Question 9

What are the stages of anesthesia?

Answer 9

I: analgesia
II: excitement, delirium
III: surgical anesthesia
IV: medullary paralysis and death

Question 10

Describe the usefulness of knowing the oil:gas coefficient and blood:gas coefficient.

Answer 10

The oil:gas coefficient tells you potency, while the blood:gas coefficient tells you speed of onset and offset.

Question 11

There are four phases of anesthesia uptake. List them and explain the properties that affect each.

Answer 11

• Phase I: inhalation (lung factors / ventilation rate)
• Phase II: uptake of blood from alveoli
• Phase III: uptake from blood to tissues
• Phase IV: distribution to tissues

Question 12

Nitrous oxide has a _____________ blood:gas coefficient than the halogenated general anesthetics.

Answer 12

lower

Question 13

The initial rise in arterial concentration of anesthetic _____________ with increase in pulmonary blood flow.

Answer 13

decreases

Question 14

True or false: the primary route of elimination for volatile anesthetics is hepatic.

Answer 14

False –you breathe it out

Question 15

The only gaseous anesthetic is ______.

Answer 15

nitrous oxide

Question 16

What is the concentration effect of N2O?

Answer 16

N2O gets taken up faster than expected.

Question 17

Describe diffusion hypoxia.

Answer 17

When anesthetic is terminated, the leaving N2O pushes oxygen out of the alveoli.

Question 18

Which of the halogenated compounds has the lowest risk of hepatotoxic and nephrotoxic effects?

Answer 18

Isoflurane

Question 19

The therapeutic indices of general anesthetics are __________.

Answer 19

extremely narrow –typically 2-4, meaning only twice the effective dose can kill someone

Question 20

How is it possible to use general anesthetics with such a narrow therapeutic index?

Answer 20

There is a very steep dose-response curve, such that 99% of patients are anesthetized at 1.3 MAC.

Question 21

What advantage did halothane have over the previous surgical anesthetic in use?

Answer 21

It is not flammable, and the previous anesthetic in common use –cyclopropane – was, occasionally resulting in operating room explosions.

Question 22

Summarize the evidence that suggests that there is no receptor for volatile anesthetics.

Answer 22

• Drugs with specific receptor targets are effective at around 0.1 mM, while general anesthetics need to be at roughly 100 mM to work.
• There is no antidote/antagonist for volatile anesthetics.

Question 23

The MAC is ___________ to the oil:gas coefficient.

Answer 23

inversely proportional

Question 24

It is thought that volatile anesthetics interact with the _______________ of proteins.

Answer 24

lipophilic parts –both in transmembrane and intracellular proteins

Question 25

True or false: general anesthetics lead to conduction block.

Answer 25

False. Anesthetized patients have normal action potential conduction.

Question 26

Why is anesthetic uptake by fatty tissues slow?

Answer 26

Because the solubility of anesthetics in fat is high, and they can thus take in much anesthetic; also, fatty tissues are less well perfused than fat.

Question 27

Describe the second-gas effect.

Answer 27

N2O gets pulled in faster than expected, and it can pull in another gas if co-administered (such as isoflurane).

Question 28

For what side effects was chloroform discontinued?

Answer 28

Hepatotoxicity and cardiac arrhythmias

Question 29

Desflurane has the benefit of _______________ but the drawback of _______________.

Answer 29

no liver toxicity; pungent odor which causes throat irritation

Question 30

What is pharmacodynamically important about the acetylcholine-blocking drugs?

Answer 30

They don’t cross the BBB! (Otherwise they would have terrible cortical effects.)