28: Principles of General Anaesthesia

Question 1

What are the disired effects you would want from a general anesthetic agent?

Answer 1

• Loss of consciousness
• Suppression of reflex responses
• analgesia
• Muscle relaxation
• Amnesia

Question 2

What are the effects that all general anaesthetic agents have in common?

At which dosages do they occur?

Answer 2

1. Loss of consciousness
   
   • at low concn
2. Suppression of reflex responses
   
   • at high concn

Question 3

What are the two borad types of general Anaesthetic agents ?

Answer 3

1. Gaseous/ Inhaled
   
   • N₂O
   • Diethyl Ether
   • Halothane
   • Enflurane
2. IV
   
   • Propofol
   • Etomidate

Question 4

What is the structural relationship of General Anaestetic agents?

Answer 4

Generally: barely anything structurally in common

Question 5

Explain the Lipid Hypothesis of GA and its limitations

Answer 5

Generally: It could be observed the more lipid soluble a GA is the more potent it is

• –> Development of Lipid Theory for MOA
  
  • GA disrupt Lipid membranes
  • BUT
    
    • at relevant concentrations only minimal changes to lipid membranes could be observed
    • not clear how this change would impact membrane proteins

Question 6

What are the two general MOAs of General Anaesthetic agents?

Answer 6

Overall: Many targets+ very compex

They can either

1. Alter synaptic function (most effects)
2. or directly Reduced neuronal excitability

Question 7

What are the effects of GA on GABA Neurons?

Which subtype is important?

Answer 7

Generally: GA (almost all) enhance GABA_{<strong>A</strong>} receptor activity

(Altering synaptinc function)

Question 8

What are the molecular targets of GA that cause supression of reflexes?

Answer 8

1. ß₃ Subunit of GABA_A receptor (rather in brain)
2. alpha 1 subunit of Glycine recpeptor (in spinal chord)

Question 9

What is the molecular target of GA that cause amnesia?

Answer 9

Enhancement of Alpha 5 Subunit of GABA_A receptor

Question 10

What is the molecular MOA of action of N₂O?

Answer 10

Blocks exitory NMDA-type glutamate receptor (probably competes with co-agonist glycine)

Question 11

What is the molecular target of GA that cause analgesia?

Answer 11

Supression of neuroanal nicotinic Ach receptors

(alteraltion of synapse function)

Question 12

What is the molecular target of GA that interferes with conciousness?

Answer 12

E.g. TREK (backround leak) K+ channels ehancement –> Hyperpolerisation of Neurones (change in neuronal exitability)

Question 13

What is the difference in the MOA between IV and gaseous general Anaesthetics?

Answer 13

Both MOA are compex and have many targets but generally

• IV= more specific targets
• Inhaled= more general+ all together more targets

Question 14

Where are glycine receptors located and what is their effect?

Answer 14

Glycine Receptor= homologous and often close to GABA receptors

• inhibitory role
• expecially in lower brainstem+ spinal chord
• might play a role in volatile (= gaseous) GA effects

Question 15

What is the Blood: gas partition coefficient ?

Answer 15

It is the distribution of anesthetic concentrations in the blood and alveolar space when partial pressures in the two compartments are equal

(concentrations can be different at same partial pressure because of different phases (liquid vs gas)

Question 16

What are the characteristics of a hight blood:gas partition coefficient?

Answer 16

High blood:gas partition coefficient=

• higher potency
• high solubility in the blood
  
  • more needs to be dissolved in blood leading to
• slower speed of onset
• slow elimination (because more is soluble in blood)

Question 17

What are the characteristics of a low blood:gas partition coefficient?

Answer 17

Low blood:gas partition coefficient

• lower potency of drug
• less soluble therfore
  
  • less needs to be dissolved in blood for effect
• Faster onset
• Fast elinimation

Question 18

Explain the Neuroanatomical relation of effect of loss of conciousness of general anesthesia

Answer 18

• decreases RAS activity
  
  • via activation of GABA_A receptors that decrease sensory input from cortex to RAS and
  • Activate TREK channels in RAS–> hyperpolarisation
• Depress
  • Reticular activating neurons in the Midbrain reticular formation
  • Thalamus
  • Cortex

Question 19

Explain the Neuoanatomical relation of General anaesthetics and Suppression of reflex responses

Answer 19

Via GABA and Glycine receptors in the spinal chord

• reduce reflex pathway in spinal chord
  
  • disconnect spinal chord from brain

Question 20

Expaimn the Neuroanatomical relation of Amnesia in General Anaesthetics

Answer 20

↓ synaptic transmission in hippocampus/amygdala via alpha 5 SU of GABA_A receptors

Question 21

What are the advantages of Inhalation anaesthetics vs IV anaesthetics?

Answer 21

• Good control (of time and depth of anaesthesia)
  
  • because of rapid elimination

Question 22

What are the advantages and disadvantages of the use of IV anaesthetics over inhalation anaesthetics

Answer 22

• fast induction
• less coughing/ exitatiory phenomena
  
  • but: slow eliminaition therfore less control once adminstered

Question 23

How is generally anaestesia managed in hospital?

Answer 23

1. Induction with IV anaestetic –> fast onset (e.g. Propophol)
2. Maintainance with Inhalation Anaesthetic –> good control
3. Administration of additional drugs for more effects (dependant on need)
   
   • analgesia -opioids
   • Muslce relaxation - nmj blocking
   • amnesia - benzodiazepine