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Nervous System: Unit IV > General Anesthetics I & II > Flashcards

General Anesthetics I & II Flashcards

1
Q

General purpose of general anesthetic

A
  • 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
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2
Q

MOA of inhaled anesthetics

A
  • 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
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3
Q

Classes of inhaled general anesthestics

A
  • inorganic gases
  • ethers (diethyl ether)
  • hydrocarbons
  • chlorinated hydrocarbons
  • fluorinated hydrocarbons
  • fluorinated ethers
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4
Q

Inorganic gases: examples

A
  • xenon
  • nitrous oxide
  • nitrogen
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5
Q

Hydrocarbons: examples

A
  • cyclopropane
  • ethylene
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6
Q

Chlorinated hydrocarbons: examples

A
  • chloroform
  • tricholoroethylene
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7
Q

Fluorinated hydrocarbons: examples

A

halothane

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8
Q

Fluorinated ethers: examples

A
  • enflurane
  • isoflurance
  • desflurane
  • sevoflurane
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9
Q

Classes of IV general anesthetics (+examples)

A
  • Barbituates
    • thiopental
  • Benzodiazepines
    • diazepam
  • Opioid analgesics
    • morphine
    • fentanyl
  • Glutamate receptor agent
    • ketamine
  • Misc. agents
    • propofol
    • etomidate
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10
Q

Lipid theory of general anesthetic action

A
  • 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
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11
Q

Protein theory of general anesthetic mechanism

A
  • 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
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12
Q

Physicochemical properties of inhaled general anesthetics vs. potency

A
  • 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
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13
Q

Action of inhaled general anesthetics @ nervous system

A
  • depress neuronal excitability @ CNS
  • occurs via potentiation of GABAA receptor activity
  • ==> increased duration of inhibitiory postsynaptic potentials ==> inhibition @ CNS
  • conduction block is NOT believed to underlie anesthesia
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14
Q

Development of General Anesthetic Action

A
  • 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
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15
Q

Phases of Stage III anesthesia

A
  • 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
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16
Q

Time course of surgical anesthesia

A
  • 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
17
Q

Factors that impact the rate at which anesthetic reaches brain

A

(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)

18
Q

Factors that determine rate of recovery from anesthesia

A
  • same as rate of onset:
  • concentration
  • AVR
  • CO
  • blood:gas coefficient
  • potency
19
Q

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

A
  • 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
20
Q

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

A
  • 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
21
Q

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

A
  • 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
22
Q

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

A
  • @ 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
23
Q

Major process of general anesthetic elimination

A
  • anesthetic is primarily cleared by the lungs
  • metabolism @ liver is generally not important in terminating anesthetic action
24
Q

Nitrous oxide (N2O): advantages, disadvantages

A
  • +
    • 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
25
Q

Diethyl ether: advantages, disadvantages

A
  • not currently used in practice
  • +
    • “complete anesthetic”
    • good analgesic
  • -
    • flammable/explosive
    • excessive respiratory tract secretions ==> choking
  • slow induction/recovery
26
Q

Chloroform: advantages, disadvantages

A
  • no longer in common use
  • -
    • ==> cardiac arrhythmias
    • ==> hepatotoxicity
27
Q

Halothane: advantages, disadvantages

A
  • +
    • 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)
28
Q

Tx for malignant hyperthermia

A
  • give dantrolene (muscle relaxant)
  • ice water immersion
  • use IV anesthetic if hx indicates risk for MH
29
Q

Enflurane: advantages, disadvantages

A
  • +
    • excellent analgesic
    • induction/recovery moderately fast
    • good muscle relaxant
  • -
    • ==> seizures (@ induction/recovery)
    • some CV effects/hepatotoxicity (but less than halothane)
30
Q

Isoflurane: advantages, disadvantages

A
  • 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
31
Q

Desflurane: advantages, disadvantages

A
  • +
    • 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
32
Q

Sevoflurane: advantages, disadvantages

A
  • +
    • high potency + low blood:gas coefficient ==>
    • rapid onset/recovery + adjustment of anesthetic depth
    • pleasant odor ==> can be used for induction
  • -
    • chemical instability ==> renal toxicity
33
Q

Thiopental: MOA/use

A
  • IV general anesthetic
  • ultra-short acting barbiturate
  • MOA:
    • Potentiates GABAA receptor activity ==> prolonged IPSPs ==> depression of CNS
  • Use:
    • commonly used for induction
34
Q

Propofol: MOA

A
  • IV general anesthetic
  • MOA:
    • potentiates GABAA receptor activity
    • rapid-onset anesthetic
35
Q

Etomidate: MOA, use

A
  • nonbarbiturate hypnotic w/out analgesic properties
  • MOA:
    • potentiates GABAA receptor activity
  • Use:
    • induction of general anesthetsia
    • “balanced anesthesia”
36
Q

Ketamine: MOA, use

A
  • Phencyclidine (PCP) derivative
  • MOA:
    • antagonist of NMDA-subtype glutamate receptor
    • inhibits excitatory glutamatergic synaptic transmission @ CNS
    • NO action @ GABAA
  • Indicated in asthmatic patients
37
Q

Rationale for use of multiple agents to achieve surgical anesthesia

A
  • 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
38
Q

Methods of application of inhaled anesthetics

A
  • 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.
39
Q
A

Nervous System: Unit IV (26 decks)

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