(PM3B) General Anaesthetics Flashcards
What is Lister’s carbolic spray?
Antiseptic
What are the aims of general anaesthesia?
(1) Loss of consciousness (+ amnesia)
(2) Analgesia
(3) Muscle relaxation (immobility)
Give an example of a halogenated hydrocarbon.
Isoflurane
Give an example of a barbiturate.
Thiopental
What is lipid theory?
Idea that general anaesthetics acted by integrating into the plasma membrane
How is anaesthetic action measured?
Minimum alveolar concentration (MAC)
The concentration of vapour in the lungs that is needed to prevent movement in 50% of subjects in response to pain stimulus
Inversely proportional to potency
Lower MAC value = more potent volatile anaesthetic
What does a low MAC value indicate?
More potent volatile anaesthetic
What effect do general anaesthetics have on a cellular level?
Inhibit synaptic transmission
What are the actions of general anaesthetics on the CNS?
(1) Inhibit excitatory ion channels such as glutamate + ACh ionotropic receptors
(2) Activate inhibitory ion channels such as GABA(A) ionotropic receptors and two-pore potassium channels
i. e. to reduce excitation/ increase inhibition
How do general anaesthetics exhibit an effect on consciousness?
Act at midbrain reticular formation
How do general anaesthetics exhibit an analgesic effect?
Act at thalamic sensory relay nuclei
How do some general anaesthetics exhibit an effect on amnesia and memory?
Act on hippocampus
e.g. rohypnol
How do general anaesthetics exhibit an effect on loss of reflexes?
Acts on spinal level
Contributes to control of motor function
Leads to muscle relaxation
What effect do general anaesthetics have on the cardiovascular system?
Cause circulatory depression
Decreases cardiac contractility
What effect do general anaesthetics have on the respiratory system?
Profound respiratory depression
What effect do general anaesthetics have on muscles?
Action at neuromuscular junction (NMJ)
Causes muscle relaxation
What are the stages of general anaesthesia?
(1) Premedication
(2) Induction
(3) Maintenance
(4) Pain relief
(5) Muscle relaxation
What is premedication?
Combined drug treatment 1-3 Horus prior to anaesthesia
What is the purpose of premedication?
(1) Reduce anxiety/ pain/ secretions/ vagal reflexes/ postoperative nausea + vomiting
(2) Increase amnesia/ hypnotic effects of anaesthesia
What drug classes are used in premedication?
(1) Benzodiazepines
- e.g. diazepam
- increases inhibitory GABA release
- sedative + anxiolytic effect
(2) mAChR antagonist
- e.g. atropine
- prevents vagal reflexes + secretion
(3) Opioid receptor antagonist
- e.g. morphine
- sedative + reduction of pain
(4) PPI
- metoclopramide
- limits nausea + vomiting
What is induction?
IV bolus agents
Induce loss of consciousness + amnesia
What is the purpose of induction?
To induce loss of consciousness + amnesia
What drugs are used in induction?
(1) Propofol
- activate GABA(A) receptors
- promote inhibition
(2) Barbiturates - e.g. sodium thiopental
- activate GABA(A) receptors
- promote inhibition
What are some of the properties of drugs used for induction?
(1) Small
(2) Highly lipophilic
(3) Rapid distribution
(4) Fast onset
- ~20 seconds for circulatory blood to reach brain
(5) Action terminated by distribution into large compartments
- e.g. muscle
(6) Preferable to inhalation agents which have a slower onset of action
What is propofol?
An induction drug
Favourable due to rapid metabolism
Lack of hangover effect
What is thiopental?
An induction drug
Only remaining widely used barbiturate
Potent + acts within ~20 seconds
Lasts 5-10 minutes due to rapid metabolism
Can accumulate in fat which can cause a hangover effect
Associated with profound respiratory depression
What is etomidate?
An induction drug
Favoured due to high therapeutic index
Lack of respiratory/ cardiovascular side effects because of high therapeutic index
What is the only drug that blocks excitatory glutamate receptors?
Ketamine
NMDA glutamate antagonist
Describe the onset of action of ketamine.
2-5 minutes
Relatively slow
What effects does ketamine have in terms of anaesthesia?
Dissociative anaesthesia
- sensory loss
- analgesia
Can cause dysphoria + hallucination
When it ketamine typically used in anaesthesia?
Paediatric medicine
Dysphoria + hallucination are less pronounced in children
What is maintenance, with regard to anaesthesia?
Volatile inhalation agents
Used to maintain loss of consciousness + amnesia
What drugs are used for maintenance in anaesthesia?
(1) Isoflurane
(2) Nitrous oxide
(3) Halothane
What are some properties of maintenance drugs?
(1) Inhaled gases have fast onset + offset of action
- allows control of depth of anaesthesia
(2) Inhaled general anaesthetics freely cross BBB
- Kinetics are determined by rate of transfer from inspired air into blood
(3) Better than IV due to rapid elimination
(4) Fewer side effects than highly sedative drugs
- e.g. morphine/ hyoscine
What is halothane?
Maintenance drug
Potent
- can lead to cardiovascular/ respiratory side effects
Can sensitise cardiac tissue to adrenaline
- can lead to dysrhythmia
Can cause hepatotoxicity
Hangover effect associated with high deposition in fat
What is nitrous oxide?
Laughing gas – Maintenance drug
Low potency
Typically used in combination
Used for childbirth
What is isoflurane?
Maintenance drug
Halogenated ether
Most commonly used inhalation anaesthetics
What is pain relief, with regard to anaesthesia?
IV opioids
Used to provide analgesia
What drugs are used in pain relief in analgesia?
(1) Morphine
(2) Fentanyl
What are some side effects of opioids?
(1) Sedation
(2) Respiratory depression
(3) Nausea + vomiting
(4) Bronchospasm precipitation
(5) Anaphylaxis precipitation
What is muscle relaxation, with regard to anaesthesia?
Agents acting at nAChRs at NMJ
Cause immobility during surgery
How do neuromuscular blocking agents work?
(1) Competitive antagonists of nAChRs
- competitive blockers
(2) Agonists which cause depolarising lock of the muscle endplate
- depolarising blockers
What are some examples of competitive antagonists of nAChRs?
(1) Atracurium
(2) Pancuronium
(3) Vecuronium
What does binding of competitive antagonists of nAChRs lead to?
(1) Na+ entry
(2) Depolarises postsynaptic membrane
(3) Causes an excitatory postsynaptic potential
(4) Generates an action potential
- if threshold is reached
Why are competitive antagonists of nAChRs used in obstetrics?
Do not cross the placenta
How are competitive antagonists of nAChRs administered?
IV
What is the duration of action of atracurium?
<60 minutes
What is the duration of action of vecuronium?
<60 minutes
What is the duration of action of pancuronium?
> 60 minutes
What is the duration of action of rocuronium?
<60 minutes
How is muscle paralysis caused by depolarising nAChR blockers?
Continual stimulation of NMJ
Causes muscle contraction due to depolarisation
Cannot repolarise as Na+ channels cannot inactivate
What is an example of a depolarising nAChR blocker?
Suxamethonium/ succinylcholine
Describe the duration of action of suxamethonium.
Short-acting
~10 minutes
As it is rapidly hydrolysed by cholinesterases
What is the purpose of a combination of drugs being given in general anaesthesia?
(1) Rapid onset
(2) Rapid recovery
(3) Avoids periods of semi-consciousness
(4) No undue disruption of homeostasis
