W21 General Anaesthetics (SM)

Question 1

Anaesthesia: “loss of sensation/consciousness”
What are anaesthetic agents used for?
What are neuromuscular blocking agents used for?
What are analgesics used for?

Answer 1

• Anaesthetic agents to produce unconsciousness
• Neuromuscular blocking agents
  -for muscle relaxation
• Analgesics
  -For pain relief

Question 2

Stages of anaesthesia?

Answer 2

Stage 1- Analgesia
* Conscious, drowsy, antinociception, amnesia

Stage 2- Excitement
* Loss of consciousness but delirium, irregular cardio respiration, apnoea, spasticity, gagging, vomiting

Stage 3- Anaesthesia
* Regular respiration, loss of reflux and muscle tone

Stage 4- Medullary Paralysis
* Depression of cardiorespiratory and death

Question 3

Types of Anaesthetic agents? (3)

Answer 3

1. General Anaesthesia
   *Loss of sensation throughout the body– often used during major surgical procedures
2. Regional Anaesthesia
   *Loss of sensation to a specific region of the body– spinal, epidural and peripheral nerve block (orthopaedic surgery, c-section, gynaecological procedures)
3. Local Anaesthesia
   *small area of the body is numbed, fully conscious –often used during minor procedures (dental procedures, minor sports injuries)

Question 4

General anaesthetics -how it should work? (3)

Answer 4

1. Loss of conscious awareness
2. Loss of response to noxious stimuli
3. Reversibility

Question 5

Goals of General Anaesthetics?
Types of General anaesthetics?

Answer 5

• Induction of sleep
• Maintenance of sleep
• Waking up from sleep

Intravenous anaesthetics
Inhalation anaesthetics

Question 6

Inhalational anaesthetics:
What are some examples of treatment?

Answer 6

– Gases or vapours (administered via vaporizers)
(usually, halogenated ethers or hydrocarbons e.g. halothane, isoflurane)
– Controllable, rapid blood-gas exchange

• N2O
  – rapid, low potency, in combination, obstetrics, analgesic, teratogenic,
• halothane
  – vet use, developing countries, hepatotoxic, hangover
• enflurane
  – fast on and off, lower toxicity, epileptogenic
  – isoflurane
  – non-epileptogenic, cardio and respiratory effects
  – desflurane
  – v. fast on and off, day surgery
  – sevoflurane
  – fast, potent, maybe hepatotoxic
  – ether (and derivatives), cyclopropane, chloroform
  – largely obsolete, many side effects, explosive

Question 7

How GAs work?
Potency: What is the definition of MAC?

Answer 7

Minimum Alveolar Concentration- The concentration required to prevent 50% of patients moving when subjected to surgical midline incision

Question 8

How GAs work?
What is Lipid theory?

Answer 8

1. Lipid theory (Critical volume hypothesis & perturbation theory)
   - Overton and Meyer (1901)
2. Linear relationships (inhaled anaesthetics potency and lipid solubility)
   Higher lipid solubility= Higher level of anaesthesia

So a highly potent drug will have a high Oil/Gas Partition co-efficient but a low MAC

2. Disruption of ion channel functions and disruption of annular lipids associations with ionic channels
   - A drug with a high lipid solubility will sit inbetween the phospholipid bilayer and cause it to stretch
   - Sodium ion channels disrupted so AP is inhibited

Question 9

How GAs work?
What receptors do they act on?

Answer 9

• Receptors
  – Inhibitory – GABA A, glycine (enhance)
  – Excitatory - nAch, NMDA (inhibit)
• Anaesthetics interact with membrane proteins
• Receptors and ligand-gated ion channels

Question 10

Inhalational anaesthetics:
What do all volatile anaesthetics increase?

Answer 10

• All volatile anaesthetics increase the respiration rate
• Use of inhalational anaesthesia is not safe in malignant hyperthermia-susceptible patients
• Isoflurane is an irritant vapour and potent coronary artery vasodilator -causes redistribution of coronary blood flow and
  leads to contractile dysfunction, coronary steal syndrome
• Fluorine (F-) produced may cause renal impairments

Question 11

Thiopental (Positive allosteric modulator of GABA)
What is the pharmacological effect? (4)
What are the adverse effects? (3)

Answer 11

Pharmacological effect
* potentiates endogenous GABA responses
* increase the frequency of channel opening
* generalised increase in GABA inhibition
* Hypnosis!!

Adverse effects:
– Respiratory depression, apnoea
– CVS: myocardial depression, decrease
cardiac output
– Sneezing, coughing and bronchospasm

Question 12

Ketamine (NMDA receptor antagonist-
competitive)
What does it act on?
MoA?

Answer 12

Rarely used; except paediatric anaesthesia

Ligand-gated cation channels
* Depolarisation
* AP
* Excitatory action

(Glutamate binding site, Sodium, Calcium, Glutamic acid)

Ketamine competitively antagonise glutamic acid-mediated NMDA activation: Inhibition of AP

Question 13

Ketamine (act on several other targets)

Answer 13

Ketamine also interacts with opioid receptors, monoaminergic receptors, muscarinic
receptors and voltage-sensitive Ca ion channels.
Unlike other general anaesthetic agents, ketamine DOES NOT interact with GABA
receptors

Pharmacological effect
* Hypnosis (used mainly in paediatrics)
* Analgesic in emergency medicine

Adverse effects
– Increase HR, BP, CO, O2 consumption
– Increase RR, preserved laryngeal reflexes
– dissociative anaesthesia, analgesia, amnesia

Potential problems with the use
– Slow recovery
– High extraneous muscle movement
– Hallucinations, nightmares and transient
psychotic drugs

Question 14

What are the Criteria for selection induction agent?

Answer 14

Absolute contraindication ( Hypersensitivity
Porphyria)
Patient-related factors? ( Cardiovascular Health
Respiratory Health CNS health (epilepsy)
Drug-related factors? Drug-Food, Drug-Drug
or other interactions (Egg allergy and Propofol)