L21 anaesethesisa

Question 1

Anaesthesia

Answer 1

without sense / loss of sensation

Question 2

Anaesthetic

Answer 2

• a drug that produces anaesthesia

Question 3

Local anaesthesia

Answer 3

• loss of sensation to a small part of the body
• e.g., dental procedure
• awake
• voltage-gated sodium channel GABA(A)

Question 4

Regional anaesthesia

Answer 4

• loss of sensation to a large part of the body
• e.g., epidural for labour
• can be awake
• voltage-gated sodium channel GABA(A)

Question 5

General anaesthesia

Answer 5

• total lack of sensation
• unconsciousness
• e.g., major surgery
• GABA(A) receptor, NMDA receptor or two-pore domain K+ channels

Question 6

nitrous oxide (N2O)
diethyl ether
chloroform
Coefficients (all inhaled)

Answer 6

• N2O - low Blood:gas and low Oil:gas
• diethyl ether - mod Blood:gas and mod Oil:gas
• chloroform - mod Blood:gas and high Oil:gas

Question 7

blood:gas partition coefficient

Answer 7

• solubility of inhaled general anaesthetics in blood relative to air
• onset of and recovery from anaesthetic effect
• lower b:g partition coefficient → fast onset of effect

Question 8

oil:gas partition coefficient

Answer 8

• solubility of inhaled general anaesthetics in lipid relative to air
• higher oil:gas partition coefficient → higher potency of the anaesthetic

Question 9

MAC (minimum alveolar concentration) def

Answer 9

• the concentration at which 50% of subjects do not react to skin incision

Question 10

MAC (minimum alveolar concentration) info

Answer 10

• the concentration at which 50% of subjects do not react to skin incision
• expressed as a % at 1 atm
• measure potency of a volatile anaesthetic; inverse proportional to the oil:gas
  partition coefficient

Question 11

issues of Early inhalation anaesthetics

Answer 11

• slow onset of action and recovery - diethyl ether and
  chloroform
• flammable - diethyl ether
• hepatotoxicity and cardiac toxicity - chloroform
• undesirable postoperative effects - nausea, vomiting

Question 12

diethyl ether issues

Answer 12

• slow onset of action and recovery
• flammable
• undesirable postoperative effects - nausea, vomiting

Question 13

Chloroform issues

Answer 13

• slow onset of action and recovery
• hepatotoxicity and cardiac toxicity
• undesirable postoperative effects - nausea, vomiting

Question 14

an ideal inhalation anaesthetic

Answer 14

• nonflammable and nonexplosive
• minimal interactions with other drugs
• lack of unwanted effects on respiratory and cardiovascular systems
• high lipid solubility
• low blood solubility
• no hangover effects
• nontoxic, nonirritant to the airways
• analgesic
• inexpensive; long shelf life

Question 15

Stage 1 of general anaesthesia

Answer 15

• Analgesia
• without amnesia → analgesia with amnesia; remain conscious
• breathing: slow and regular
• pupil diameter - normal and responsive to light

Question 16

Stage 2 of general anaesthesia

Answer 16

• Excitation
• excitation and delirium; amnesia; unconscious
• breathing: irregular
• pupil diameter - normal and responsive to light
• not desirable

Question 17

Stage 3 of general anaesthesia

Answer 17

• Surgical anaesthesia
• subdivided into four levels of increasing depth
• breathing: regular → progressively weaker
• pupil diameter - gradual dilation, unresponsive to light

Question 18

Stage 4 of general anaesthesia

Answer 18

• Medullary depression
• loss of spontaneous respiration and progressive depression of cardiovascular reflexes
• breathing: respiratory cessation
• pupil diameter - complete dilation
• Not good

Question 19

Anaesthetics - concentration-response curves

Answer 19

consciousness → unconsciousness occurs over a narrow concentration range (propofol)

Question 20

simple, short surgical anaesthetic procedure

Answer 20

• a single anaesthetic can be used on its own

Question 21

complex surgical procedure anaesthetic

Answer 21

• ‘balanced anaesthesia’ - an array of drugs are given at various times throughout the procedure to deliver the following effects as required
  – sedation
  – analgesia
  – muscle relaxation
• MR- necessary for abdominal and thoracic surgery; mechanical ventilation is required

Question 22

‘balanced anaesthesia’

Answer 22

• an array of drugs are given at various times throughout the procedure to deliver the following effects as required
  – sedation
  – analgesia
  – muscle relaxation

Question 23

Anaesthsia timeline

Answer 23

premedication (benzodiazepines like diazepam)
↓
induction (I.V anaesthetic)
↓
muscle relaxation & intubation (neuromuscular block)
↓
maintenance of anaesthesia (IV or inhaled ana)
↓
analgesia (opioid)
↓
reversal (anticholinesterase to inhibit ACh breakdown)

Question 24

Modern general anesthetics (3)

Answer 24

Inhaled
* -flurane (volatile liquid)
* N2O (gas)
IV
* propofol
* thiopental

Question 25

-flurane main molecular targets

Answer 25

* GABA(A) receptor: ↑ * NMDA: ↓ (drug inhibit) * two-pore domain K+ channels: ↑

Question 26

thiopental main molecular targets

Answer 26

Gaba(A): ↑ – both synaptic and extrasynaptic

Question 27

propofol main molecular targets

Answer 27

Gaba(A): ↑ – both synaptic and extrasynaptic

Question 28

General anesthetics - main molecular targets

Answer 28

* GABAA receptor - both synaptic and extrasynaptic * NMDA receptor - excitatory * two-pore domain K+ channels - resting membrane potential

Question 29

Inhaled Anaesthetics - adverse effects

Answer 29

* Respiratory depression * cardiovascular depression (↓ blood pressure and heart rate) * postoperative nausea and vomiting * malignant hyperthermia * respiratory tract irritation

Question 30

malignant hyperthermia

Answer 30

* Adverse from inhaled anaesthetic * defect in the ryanodine receptor (RYR1) * excessive Ca2+ release from sarcoplasmic reticulum → heat production in skeletal muscles

Question 31

Intravenous Anaesthetics - adverse effects

Answer 31

* Respiratory depression * cardiovascular depression (↓ blood pressure and heart rate) * postoperative nausea and vomiting * pain at injection site

Question 32

blood:gas partition coefficient simple

Answer 32

* onset of and recovery from anaesthetic effect

Question 33

oil:gas partition coefficients simple

Answer 33

* potency of an anaesthetic

Question 34

pharmacokinetics: Modern inhalation anaesthetics

Answer 34

* mostly eliminated in expired air * alveolar ventilation * cardiac output

Question 35

sevoflurane

Answer 35

* Low B:G * HigG * fast induction and recovery * least respiratory irritation

Question 36

thiopental Induction, recovery & notes

Answer 36

* fast * slow * pain injection site, respiratory depression, not for continuous infusion = accumulation

Question 37

Propofol Induction, recovery & notes

Answer 37

* fast * fast * pain injection site, respiratory depression * continuous infusion

Question 38

total intravenous anaesthesia

Answer 38

the anaesthetic is used for both induction and maintenance of anaesthesia

Question 39

Thiopental not continuous infusion why

Answer 39

* highly lipophilic * goes to liver and brain first * Hangover effect: blood concentration drops slowly, saturable metabolism * Stored and then will slowly be released to systemic circulation and show effects after anaesthetic is needed.