General Anesthetics I & II

Question 1

General purpose of general anesthetic

Answer 1

• suppress pain/knowledge of pain during surgery
• = analgesia + amnesia + LOC + suppressed sensory and autonomic reflexes
• rapid and smooth onset w/rapid recovery upon termination of drug administration
• wide margin of safe use

Question 2

MOA of inhaled anesthetics

Answer 2

• not completely understood
• no single “receptor”
• uncharged, nonpolar molecules

1. drugs act via action on lipid component of nerve cell membrane
2. drugs act @ protein component of membrane

Question 3

Classes of inhaled general anesthestics

Answer 3

• inorganic gases
• ethers (diethyl ether)
• hydrocarbons
• chlorinated hydrocarbons
• fluorinated hydrocarbons
• fluorinated ethers

Question 4

Inorganic gases: examples

Answer 4

• xenon
• nitrous oxide
• nitrogen

Question 5

Hydrocarbons: examples

Answer 5

• cyclopropane
• ethylene

Question 6

Chlorinated hydrocarbons: examples

Answer 6

• chloroform
• tricholoroethylene

Question 7

Fluorinated hydrocarbons: examples

Answer 7

halothane

Question 8

Fluorinated ethers: examples

Answer 8

• enflurane
• isoflurance
• desflurane
• sevoflurane

Question 9

Classes of IV general anesthetics (+examples)

Answer 9

• Barbituates
  
  • thiopental
• Benzodiazepines
  
  • diazepam
• Opioid analgesics
  
  • morphine
  • fentanyl
• Glutamate receptor agent
  
  • ketamine
• Misc. agents
  
  • propofol
  • etomidate

Question 10

Lipid theory of general anesthetic action

Answer 10

• volatile anesthetics partition into oil > water
  
  • higher oil:water partition coefficient ==> increased potency
• minimul alveolar concentration of anesthetic is inversely proportional to potency
• exert effects by partitioning lipid component of nerve cell membrane

Question 11

Protein theory of general anesthetic mechanism

Answer 11

• anesthetics act via interactiosn w/hydrophobic pockets of membrane proteins
  
  • hydrophobic domains of membrane proteins = “receptors”
• interaction w/membrane proteins may lead to decreased membrane excitability
• size cut-off for structurally-related compounds (i.e. molecules that are too large don’t have anesthetic properties) indicate that they might need to fit into pockets of specific sizes @ membrane proteins
• ESR evidence supports immobilization due to proteins in lipid membranes

Question 12

Physicochemical properties of inhaled general anesthetics vs. potency

Answer 12

• higher oil: water partition ==> more potent
• size cut-off for structurally similar molecules
• stereoselectivity of anesthetic action
• Minimal alveolar concentration of anesthetic that produces insensitivity = inversely proportional to potency

Question 13

Action of inhaled general anesthetics @ nervous system

Answer 13

• depress neuronal excitability @ CNS
• occurs via potentiation of GABA_A receptor activity
• ==> increased duration of inhibitiory postsynaptic potentials ==> inhibition @ CNS
• conduction block is NOT believed to underlie anesthesia

Question 14

Development of General Anesthetic Action

Answer 14

• descending depression: progressive loss of fxn from higher (cognition/consciousness) to lower (respiratory) levels @ CNS
• Stage I = analgesia
• Stage II = excitement, delirium
• Stage III = surgical anesthesia
• Stage IV = medullary paralysis
  
  • respiratory failure, vasomotor collapse, circulatory failure

Question 15

Phases of Stage III anesthesia

Answer 15

• Plane 1 = regular, metronomic respirations
• Plane 2 = onset of muscular relaxation, fixed pupils
• Plane 3 = good muscular relaxation, depressed excursion of intercostal muscles during respiration
• Plane 4 = diaphragmatic breathing only, dilated pupils

Question 16

Time course of surgical anesthesia

Answer 16

• Induction: time between initiation of administration of anesthetic and attainment of surgical anesthesia
• Maintenance: time during which surgical anesthesia is in effect (surgery carried out during this period)
• Recovery: time following termination of administration of anesthetic until complete recovery of patient from anesthesia

Question 17

Factors that impact the rate at which anesthetic reaches brain

Answer 17

(1) concentration of the anesthetic
in inspired air

(2) alveolar ventilation rate
(3) pulmonary blood flow (cardiac output)

(4) blood:gas partition
coefficient

(5) potency (oil:gas partition coefficient)

Question 18

Factors that determine rate of recovery from anesthesia

Answer 18

• same as rate of onset:
• concentration
• AVR
• CO
• blood:gas coefficient
• potency

Question 19

Factors that impact reaching steady-state of general anesthetic: uptake factors

Answer 19

• lung factors
  
  • over-ventilation ==> increased rate of induction
• uptake by blood from alveoli
  
  • solubility in blood/pulmonary blood flow
  • rate of approach to stage 3 is inversely proportional to PBF & solubility of gas

Question 20

Factors that impact reaching steady-state of general anesthetic: uptake into tissue factors

Answer 20

• rate of uptake into tissues depends on:

1. anesthetic gas solubility @ tissue
   
   • anesthetics ~ equally soluble in blood vs. lean tissues, but more soluble in fatty tissues ==>
   • fatty tissue = resevoir for anesthetic
2. tissue blood flow
   
   • higher blood flow ==> faster delivery
3. patrial pressures of anesthetic @ blood/tissues
   
   • rate of uptake is fast at first due to large difference in partial pressures
   • rate slows as anesthesia develops

Question 21

Factors that impact reaching steady-state of general anesthetic: tissue distribution factors

Answer 21

• vessel-rich tissue: highly vascular tissue, e.g. brain, kidney, liver, heart, endocrine
  
  • high uptake rate
• muscle tissue: muscle/skin
  
  • 2-4 hours
  • slower b/c lower perfusion compared to vessel-rich group
• fat tissue:
  
  • very slow uptake b/c high solubility and low perfusion
  • impacts recovery: longer duration anesthesia ==> longer recovery due to anesthetic loading @ fatty tissue

Question 22

General physiologic principle dictating behavior of uptake/elimination of general anesthetics

Answer 22

• @ steady state: concentration of anesthetic @ alveoli = concentration of anesthetic @ blood = concentration of anesthetic @ tissues
• during uptake: anesthetic @ alveoli is increased ==> increased @ blood ==> increased @ tissues
• during elimination: anesthetic @ alveoli is decreased (via expiration) ==> decreased @ blood ==> decreased @ tissues

Question 23

Major process of general anesthetic elimination

Answer 23

• anesthetic is primarily cleared by the lungs
• metabolism @ liver is generally not important in terminating anesthetic action

Question 24

Nitrous oxide (N₂O): advantages, disadvantages

Answer 24

• +
  
  • only true gaseous agent
  • excellent analgesic
  • rapid onset/recovery
  • increases cerebral blood flow less (consider in head injury)
• -
  
  • low potency: can’t be used alone
  • hypoxia can result after termination
  • contraindicated in pregnancy

Question 25

Diethyl ether: advantages, disadvantages

Answer 25

* not currently used in practice * + * "complete anesthetic" * good analgesic * - * flammable/explosive * excessive respiratory tract secretions ==\> choking * slow induction/recovery

Question 26

Chloroform: advantages, disadvantages

Answer 26

* no longer in common use * - * ==\> cardiac arrhythmias * ==\> hepatotoxicity

Question 27

Halothane: advantages, disadvantages

Answer 27

* + * mod-high potency * induction/recovery not prolonged * non-explosive * non-irritant (reduced respiratory secretions) * - * poor analgesic * ==\> respiratory/CV failure (arrhythmias) * ==\> liver damage (fever, nauseau ==\> hepatic failure) * ==\> malignant hyperthermia (muscle rigidity ==\> fever)

Question 28

Tx for malignant hyperthermia

Answer 28

* give dantrolene (muscle relaxant) * ice water immersion * use IV anesthetic if hx indicates risk for MH

Question 29

Enflurane: advantages, disadvantages

Answer 29

* + * excellent analgesic * induction/recovery moderately fast * good muscle relaxant * - * ==\> seizures (@ induction/recovery) * some CV effects/hepatotoxicity (but less than halothane)

Question 30

Isoflurane: advantages, disadvantages

Answer 30

* similar to enflurane; most widely used * + * more potent than enflurane * little hepatic/renal toxicity * no seizures * rapid/smooth induction/recovery * minimal CV depression * good muscle relax * - * pungent ==\> coughing

Question 31

Desflurane: advantages, disadvantages

Answer 31

* + * low blood/fatty tissue solubility * faster recovery after long duration anesthesia * no hepatotoxicity * - * pungent ==\> coughing ==\> not used for induction * contraindicated in pts susceptible to malignant hyperthermia

Question 32

Sevoflurane: advantages, disadvantages

Answer 32

* + * high potency + low blood:gas coefficient ==\> * rapid onset/recovery + adjustment of anesthetic depth * pleasant odor ==\> can be used for induction * - * chemical instability ==\> renal toxicity

Question 33

Thiopental: MOA/use

Answer 33

* IV general anesthetic * ultra-short acting barbiturate * MOA: * Potentiates GABA_A receptor activity ==\> prolonged IPSPs ==\> depression of CNS * Use: * commonly used for induction

Question 34

Propofol: MOA

Answer 34

* IV general anesthetic * MOA: * potentiates GABA_A receptor activity * rapid-onset anesthetic

Question 35

Etomidate: MOA, use

Answer 35

* nonbarbiturate hypnotic w/out analgesic properties * MOA: * potentiates GABA_A receptor activity * Use: * induction of general anesthetsia * "balanced anesthesia"

Question 36

Ketamine: MOA, use

Answer 36

* Phencyclidine (PCP) derivative * MOA: * antagonist of NMDA-subtype glutamate receptor * inhibits excitatory glutamatergic synaptic transmission @ CNS * NO action @ GABA_A * Indicated in asthmatic patients

Question 37

Rationale for use of multiple agents to achieve surgical anesthesia

Answer 37

* No single drug possesses all of the most desirable properties, * combination of drugs is used in modern anesthesiological practice to achieve optimal behavior * specific drug combinations are designed to take advantage of the desirable properties of individual drugs while attenuating undesirable side effects

Question 38

Methods of application of inhaled anesthetics

Answer 38

* Anesthetic machines → measure and control the mixture of anesthetic administered to a patient * Vaporizers are used to add volatile anesthetic to the inspired gas, and the mixture is administered to the patient via a breathing circuit.