General Anesthetics

Question 1

General anesthesia

Answer 1

altered physiologic state with:
- hypnosis
- analgesia
- amnesia
- immobility
- inhibition of autonomic and sensory reflexes
\+/- muscle relaxation

Question 2

Inhaled anesthetics chem structures

Answer 2

Nitrous oxide = inorganic gas

All others: volatile halogenated hydrocarbons/ethers

Question 3

Hydrocarbon anesthetics

Answer 3

chloroform
cyclopropane
ethylene
halothana

Question 4

Ether anesthetics

Answer 4

Diethyl ether
enflurane
methoxyflurane
isoflurane
fluoroxene
sevoflurane
desflurane

Question 5

Uptake and distribution of gen anesthetics

Answer 5

Anesthesia induced when critical concentration reached in the brain
Expressed as partial pressure: Pbr/Fbr
Depth of anesthesia determined by Pbr

Question 6

Concentration gradient - anesthetics

Answer 6

1) delivered
2) inspired (P1)
3) alveolar (PA)
4) arterial (Pa)
5) brain (Pbr)

Question 7

FA/FI

Answer 7

rate of uptake of an inhaled anesthetic
ratio of alveolar anesthetic concentration/inspired anesthetic concentration
determined by:
- solubility in blood
- partial pressure difference between alveoli and pulmonary venous blood
- alveolar ventilation

Question 8

Solubility of gen anesthetics

Answer 8

Expressed as partition coefficients (blood/gas)
Modern agents are less soluble in blood than in gas
Higher the blood/gas solubility, the longer it takes “blood pool” to fill –> the longer it takes until equilibrium reached between alveoli and blood, and eventually brain
Want low solubility to reach brain faster

Question 9

Relative solubility of gen anesthetics

Answer 9

Desflurane>nitrous oxide> sevoflurane > isoflurane > halothane

Question 10

MAC (gen anesthetics)

Answer 10

Minimal Alveolar Concentration
concentration of an inhaled anesthetic in alveoli at 1 atm that prevents movement in response to a painful stimulus in 50% of patients
~1.2 MAC prevents movement in 95% of patients

Question 11

Factors decreasing an agent’s MAC

Answer 11

increased age
low temperature
pregnancy
opioids
other anesthetics/CNS drugs

Question 12

MACs of several agents

Answer 12

Nitrous oxide: 105%
Desflurane: 6
Sevoflurane: 1.71
Isoflurane: 1.15
Halothana: 0.75

Question 13

MAC with 70% nitrous oxide

Answer 13

desflurane: 2.83
Sevoflurane: 0.66
Isoflurane: 0.5
Halothane: 0.29

Question 14

Meyer-Overton rule

Answer 14

MAC inversely correlates with lipid solubility

= the more lipid-soluble the agent, the more potent it is

Question 15

Gen anesthetics MOA

Answer 15

Facilitation of inhibition

• increase GABAa receptor-mediated transmission
• increased background (leak) K_ conductance

Inhibition of excitation
- reduce glutamate/ACh receptor-mediated transmission

Question 16

Metabolism of general anesthetics

Answer 16

Metabolites may be hepato/nephrotoxic
Degree of metabolism may influence rate of decrease in alveolar partial pressure at conclusion of anesthetic

General rule: rate of metabolism of inhaled anesthetics tend to follow solubility in blood

Question 17

Methoxyflurane metabolism

Answer 17

40-50% metabolized
chief metabolite: fluoride
Nephrotoxicity/hepatotoxicity

Question 18

Halothane metabolism

Answer 18

15-20% metabolized
chief metabolite: trifluoracetic acid
Hepatotoxicity/nephrotoxicity

Question 19

Sevoflurane metabolism

Answer 19

3% metabolized
Chief metabolite: fluoride (short lived)
increased degradation by soda lime to a vinyl ether ("Compound A")
Low potential for toxicity
Nephrotoxicity in rats

Question 20

Isoflurane metabolism

Answer 20

0.2% metabolized
chief metabolite: trifluoracetic acid
low potential for toxicity

Question 21

Desflurane metabolism

Answer 21

0.02% metabolized
resistant to metabolism
high molecular stability; no significant toxicity

Question 22

Nitrous oxide

Answer 22

0.0004% metabolized
chief metabolite: nitrogen
? toxicity of free radicles

Question 23

GA effect on CNS

Answer 23

reduced cerebral metabolic rate

• greatest with isoflurane: ?cerebral protection
• enflurane: epileptic activity in EEG

Cerebral vasodilatation

• increased cerebral blood flow
• nitrous oxide: only modest effect (low potency)

Question 24

GA effect on CV system

Answer 24

reduced arterial BP due to

• reduced CO (halothane) and/or
• reduced total PVR (e.g. isoflurane)

Ventricular arrhythmias (halothane)
- sensitization of myocardium to circulating catecholamines

N2O: mild sympathetic stimulation

• laughing gas
• rarely used due to nausea/vomiting

Question 25

GA effect on respiratory system

Answer 25

Respiratory depression - increased rate and reduced depth of breathing (tidal volume) - net effect: reduced alveolar ventilation/ increased PaCO2 - -> reduction in respiratory response to increased PaCO2 Decreased airway resistance - advantage for patients with asthma (inhibition of bronchiole smooth muscle)

Question 26

GA effect on kidneys

Answer 26

reduced renal blood flow | - low GFR, urine output

Question 27

GA effect on skeletal muscle

Answer 27

muscle relaxation potentiation of effects of nondepolarizing muscle relaxants (greatest with isoflurane)

Question 28

GA effect on uterus

Answer 28

``` Uterine relaxation (halothane and all other volatile agents) Could lead to prolonged uterine atony/severe blood loss in parturients Delivery: spinal anesthetic, not general ```

Question 29

Balanced anesthesia

Answer 29

combination of agents to maximize advantages, minimize adverse effects Combination of iv + potent inhaled drugs many anesthesiologists prefer to decrease total dose of a potent inhaled drug that a patient receives with any one of a number of iv drugs

Question 30

Thiopental uses/MOA

Answer 30

iv anesthetic barbiturate Rapid induction of hypnosis (no analgesia) facilitation of inhibitory NT via GABAa

Question 31

Thiopental pharmacokinetics

Answer 31

rapid induction in one "arm-brain circulation time" patient normally wakes up ~5 min after a single bolus injection when tissues are saturated, elimination and not redistribution determines time of emergenc t1/2 ~ 11 h

Question 32

Thiopental adverse effects

Answer 32

``` hypotension - exaggerated with hypovolemia - dose reductions necessary in elderly Respiratory depression Histamine release Arterial occlusion possible ```

Question 33

Propofol uses/MOA

Answer 33

iv anesthetic 2,6-diisopropylphenol sedation, induction, and maintenance of anesthecia (TIVA - total IV anesthesia) smooth induction, pleasant dreams, rapid, clear-headed wakening antiemetic no analgesia facilitates inhibitory transmission via GABAa

Question 34

Propofol PK

Answer 34

rapid induction similar to thiopental, even more rapid awakening (3min after iv bolus) rapid metabolism in liver, t1/2 ~1 hour no significant redistribution - useful for infusion

Question 35

Propofol adverse effects

Answer 35

pronounced hypotension - greater than with thopental - marked dose reductions necessary in elderly Respiratory depression & apnea injection pain potential for sepsis - dispensed in egg lecithin/soy bean oil use formulation soon after opening

Question 36

Ketamine uses/MOA

Answer 36

iv anesthetic PCP derivative state of "dissociative anesthesia" - patient appears conscious but unable to respond to/process sensory input little cardiorespiratory depression and maintain airway reflexes bronchodilating properties unpleasant dreams common Induction of anesthesia in trauma/shock battlefield surgery analgesia in burn patients im induction in children Antagonist at NMDA receptors (a type of glutamate receptor)

Question 37

Ketamine PK

Answer 37

rapid induction after iv bolus (slower than thiopental, propofol) hepatic metabolism t1/2 ~3 hour

Question 38

Etomidate

Answer 38

``` iv anesthetic imidazole derivative minimal effects on hemodynamics - useful for induction of unstable patients No analgesia Kinetics/MOA similar to propofol produces adrenal suppression ```