General anesthetics - sather

Question 1

What is the fundamental method of action of general anesthetics?

What else do they do?

Answer 1

GAs potentiate GABAAergic transmission (potentiate IPSP).

Also POTENTIATE glycine receptors (inhibitory)
ALso potentiate K+ TASK channels (decrease excitability by altering resting membrane potential)

[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.]

Question 2

What are the ideal characteristics of a general anesthetic?

Answer 2

Short half-life

Low blood solubility

Question 3

Describe the stages of anesthesia.

Answer 3

Stage I: analgesia

Stage II: excitement, delirium

Stage III: Surgical anesthesia. 4 subcategories

1) regular respirations
2) fixed pupils, muscular relaxation
3) depressed intercostal function
4) diaphragmatic breathing only, fixed pupils

Stage IV - Medullary paralysis (respiratory failure, cardiovascular collapse and death within minutes)

Question 4

When inducing someone (general anesthesia), in which order will the following occur: loss of temperature regulation, analgesia, loss of muscle tone, loss of consciousness, loss of pupillary light reflex (fixed pupils), respiratory failure, loss of fine motor control

Answer 4

1) loss of fine motor
2) analgesia
3) loss of temperature regulation
4) loss of consciousness
5) loss of pupillary light reflex
6) loss of muscle tone
7) respiratory failure

Question 5

Describe the differing rates of uptake from different types of blood:tissue in terms of a solubility coefficient.

Answer 5

Tissue:blood coefficients are approximately 1 for “lean tissues”

Brain, heart, muscle, skin –> same solubility as blood

Tissue:blood coefficient for fatty tissues is&raquo_space;greater than 1

[This simply means that anesthetic is ~equally soluble in blood and lean tissues, but that anesthetic is substantially more soluble in fatty tissue than in blood or lean tissues]

Question 6

What three factors are important in determining anesthetic uptake from blood–> tissues?

Answer 6

1) solubility coefficient
2) perfusion
3) concentration gradient (partial pressures blood vs tissue)

Question 7

1/MAC = ?

Answer 7

1/Minimum Alveolar Concentration = potency

MAC = concentration at which 50% of people are anesthetized against a small skin incision.

Question 8

Depth of anesthesia depends upon _____.

Answer 8

the concentration of anesthetic in the brain.

Question 9

The rate at which an effective concentration of anesthetic is reached in the brain depends upon 5 factors:

Answer 9

(1) concentration of the anesthetic in inspired air,
(2) alveolar ventilation rate,
(3) pulmonary blood flow (cardiac output),
(4) blood:gas partition coefficient, and
(5) potency (oil:gas partition coefficient).

Question 10

Does increasing the ventilation rate increase the depth of anesthesia?

Answer 10

no. only the rate at which steady state is reached.

Question 11

Gases which have a higher solubility in blood will induce anesthesia (faster or slower)?

Answer 11

Slower.

Question 12

INcreased pulmonary blood flow will (increase or decrease) general anesthetic uptake?

Answer 12

Decrease. Less time to diffuse.

Question 13

What tissues will uptake general anesthetic within (a) minutes (b) 2-4 hours (c) longer?

Answer 13

(a) vascular tissues (brain, kidney, heart, liver, endocrine glands)
(b) muscular tissues, skin
(c) fatty tissues

Question 14

The oil:gas partition coefficient is an index of GA (potency OR rate of uptake)?

Answer 14

potency.

Question 15

The blood:gas partition coefficient is related to (kinetics of GA uptake and elimination OR potency)?

Answer 15

Kinetics of uptake/elimination

Question 16

INcreasing the concentration of GA will increase the ____ of anesthesia.

Answer 16

rate

**I would assume the depth of anesthesia would also change…but this is not explicitly mentioned.

Question 17

INduction of anesthesia is faster with a (low blood solubility OR a high blood solubility)?

Answer 17

low.

Question 18

How are volatile anesthetics cleared from the body?

Answer 18

Exhalation. So the respiratory rate and cardiac output will determine the rate of clearance.

Question 19

Can N2O be used as a sole anesthetic agent?

Answer 19

NO. produces pretty good analgesia, but the concentration cannot get high enough to produce anesthesia.

Question 20

Why is the uptake rate of N2O faster than expected?

Answer 20

the Concentration Effect. Essentially, more N2O gets taken up due to rapid absorption across the alveoli.

Question 21

What are two really good reasons Halothane is no longer used as an anesthetic agent?

Answer 21

1) Hepatotoxic. For ∼1/10,000, 2-5 days after anesthesia, fever, anorexia and nausea/vomiting Death occurs in 50% of these patients
2) Malignant hyperthermia. Dantrolene, ice bath. Signs are muscle rigidity, temp spike.

Question 22

What is the most widely used inhalational anesthetic?

Answer 22

Flurothane.

Question 23

Why is flurothane so great?

Answer 23

Rapid induction (avoid stage II)
Less organ toxicity
Good muscle relaxant
Minimal myocardial depression

Question 24

What is one problem with flurothane?

What is the workaround?

Answer 24

Pungent odor causes cough.

So you induce with propofol, then use flurothane.

Question 25

Sevoflurane doesn’t cause cough. Why isn’t it used instead of flurothane?

Answer 25

Kidney toxicity

Mostly used for induction

Question 26

circulatory failure occurs at ____ the effective concentration for surgical anesthesia

Answer 26

only 2-4x

Question 27

In practice, what factor of MAC is used for general anesthesia?

Answer 27

0.8-1.3 MAC

**99% of ppl have no response to pain at 1.3 MAC

Question 28

What 6 categories of drug might be used during a typical surgical procedure?

Name the category and a specific drug

Answer 28

1) Anti-anxiety agent: (BDZ, diazepam)
2) Induction agent: (Thiopental)
3) Analgesic: (Fentanyl)
4) Neuromuscular blocker (vecuronium)
5) Anticholinergic drugs (glycopyrrolate, atropine, scopolamine)
6) Anti-emetic (ondansetron)

Question 29

Why is an anticholinergic administered during surgery?

Answer 29

reduce GA-induced hypotension, bradycardia, and excess salivary secretions that can choke patient during anesthesia (–> glycopyrrolate, atropine, scopolamine)

Question 30

Why are anesthetic agents combined?

Answer 30

Addition of MAC (eg .5 + .5 = 1) allows an additive effect of anesthesia without additive effects of side effects.

So this is commonly done.