L21 anaesethesisa Flashcards
Anaesthesia
without sense / loss of sensation
Anaesthetic
- a drug that produces anaesthesia
Local anaesthesia
- loss of sensation to a small part of the body
- e.g., dental procedure
- awake
- voltage-gated sodium channel GABA(A)
Regional anaesthesia
- loss of sensation to a large part of the body
- e.g., epidural for labour
- can be awake
- voltage-gated sodium channel GABA(A)
General anaesthesia
- total lack of sensation
- unconsciousness
- e.g., major surgery
- GABA(A) receptor, NMDA receptor or two-pore domain K+ channels
nitrous oxide (N2O)
diethyl ether
chloroform
Coefficients (all inhaled)
- 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
blood:gas partition coefficient
- 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
oil:gas partition coefficient
- solubility of inhaled general anaesthetics in lipid relative to air
- higher oil:gas partition coefficient → higher potency of the anaesthetic
MAC (minimum alveolar concentration) def
- the concentration at which 50% of subjects do not react to skin incision
MAC (minimum alveolar concentration) info
- 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
issues of Early inhalation anaesthetics
- slow onset of action and recovery - diethyl ether and
chloroform - flammable - diethyl ether
- hepatotoxicity and cardiac toxicity - chloroform
- undesirable postoperative effects - nausea, vomiting
diethyl ether issues
- slow onset of action and recovery
- flammable
- undesirable postoperative effects - nausea, vomiting
Chloroform issues
- slow onset of action and recovery
- hepatotoxicity and cardiac toxicity
- undesirable postoperative effects - nausea, vomiting
an ideal inhalation anaesthetic
- 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
Stage 1 of general anaesthesia
- Analgesia
- without amnesia → analgesia with amnesia; remain conscious
- breathing: slow and regular
- pupil diameter - normal and responsive to light
Stage 2 of general anaesthesia
- Excitation
- excitation and delirium; amnesia; unconscious
- breathing: irregular
- pupil diameter - normal and responsive to light
- not desirable
Stage 3 of general anaesthesia
- Surgical anaesthesia
- subdivided into four levels of increasing depth
- breathing: regular → progressively weaker
- pupil diameter - gradual dilation, unresponsive to light
Stage 4 of general anaesthesia
- Medullary depression
- loss of spontaneous respiration and progressive depression of cardiovascular reflexes
- breathing: respiratory cessation
- pupil diameter - complete dilation
- Not good
Anaesthetics - concentration-response curves
consciousness → unconsciousness occurs over a narrow concentration range (propofol)
simple, short surgical anaesthetic procedure
- a single anaesthetic can be used on its own
complex surgical procedure anaesthetic
- ‘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
‘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
Anaesthsia timeline
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)
Modern general anesthetics (3)
Inhaled
* -flurane (volatile liquid)
* N2O (gas)
IV
* propofol
* thiopental
-flurane main molecular targets
- GABA(A) receptor: ↑
- NMDA: ↓ (drug inhibit)
- two-pore domain K+ channels: ↑
thiopental main molecular targets
Gaba(A): ↑
–both synaptic and extrasynaptic
propofol main molecular targets
Gaba(A): ↑
–both synaptic and extrasynaptic
General anesthetics - main molecular targets
- GABAA receptor - both synaptic and extrasynaptic
- NMDA receptor - excitatory
- two-pore domain K+ channels - resting membrane potential
Inhaled Anaesthetics - adverse effects
- Respiratory depression
- cardiovascular depression (↓ blood pressure and heart rate)
- postoperative nausea and vomiting
- malignant hyperthermia
- respiratory tract irritation
malignant hyperthermia
- Adverse from inhaled anaesthetic
- defect in the ryanodine receptor (RYR1)
- excessive Ca2+ release from sarcoplasmic reticulum → heat production in skeletal muscles
Intravenous Anaesthetics - adverse effects
- Respiratory depression
- cardiovascular depression (↓ blood pressure and heart rate)
- postoperative nausea and vomiting
- pain at injection site
blood:gas partition coefficient simple
- onset of and recovery from anaesthetic effect
oil:gas partition coefficients simple
- potency of an anaesthetic
pharmacokinetics: Modern inhalation anaesthetics
- mostly eliminated in expired air
- alveolar ventilation
- cardiac output
sevoflurane
- Low B:G
- HigG
- fast induction and recovery
- least respiratory irritation
thiopental
Induction, recovery & notes
- fast
- slow
- pain injection site, respiratory depression, not for continuous infusion = accumulation
Propofol
Induction, recovery & notes
- fast
- fast
- pain injection site, respiratory depression
- continuous infusion
total intravenous anaesthesia
the anaesthetic is used for both induction and maintenance of anaesthesia
Thiopental not continuous infusion why
- 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.
