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
2
Q
MOA of inhaled anesthetics
A
- not completely understood
- no single “receptor”
- uncharged, nonpolar molecules
- drugs act via action on lipid component of nerve cell membrane
- drugs act @ protein component of membrane
3
Q
Classes of inhaled general anesthestics
A
- inorganic gases
- ethers (diethyl ether)
- hydrocarbons
- chlorinated hydrocarbons
- fluorinated hydrocarbons
- fluorinated ethers
4
Q
Inorganic gases: examples
A
- xenon
- nitrous oxide
- nitrogen
5
Q
Hydrocarbons: examples
A
- cyclopropane
- ethylene
6
Q
Chlorinated hydrocarbons: examples
A
- chloroform
- tricholoroethylene
7
Q
Fluorinated hydrocarbons: examples
A
halothane
8
Q
Fluorinated ethers: examples
A
- enflurane
- isoflurance
- desflurane
- sevoflurane
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
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
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
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
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
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
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
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:
- anesthetic gas solubility @ tissue
- anesthetics ~ equally soluble in blood vs. lean tissues, but more soluble in fatty tissues ==>
- fatty tissue = resevoir for anesthetic
- tissue blood flow
- higher blood flow ==> faster delivery
- 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
- low blood/fatty tissue solubility
- -
- 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
