(PM3B) General Anaesthetics Flashcards by David Vincent-Waterson

What is Lister’s carbolic spray?

Antiseptic

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What are the aims of general anaesthesia?

(1) Loss of consciousness (+ amnesia)
(2) Analgesia
(3) Muscle relaxation (immobility)

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Give an example of a halogenated hydrocarbon.

Isoflurane

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Give an example of a barbiturate.

Thiopental

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What is lipid theory?

Idea that general anaesthetics acted by integrating into the plasma membrane

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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

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What does a low MAC value indicate?

More potent volatile anaesthetic

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What effect do general anaesthetics have on a cellular level?

Inhibit synaptic transmission

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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

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How do general anaesthetics exhibit an effect on consciousness?

Act at midbrain reticular formation

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How do general anaesthetics exhibit an analgesic effect?

Act at thalamic sensory relay nuclei

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How do some general anaesthetics exhibit an effect on amnesia and memory?

Act on hippocampus

e.g. rohypnol

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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

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What effect do general anaesthetics have on the cardiovascular system?

Cause circulatory depression

Decreases cardiac contractility

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What effect do general anaesthetics have on the respiratory system?

Profound respiratory depression

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What effect do general anaesthetics have on muscles?

Action at neuromuscular junction (NMJ)

Causes muscle relaxation

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What are the stages of general anaesthesia?

(1) Premedication
(2) Induction
(3) Maintenance
(4) Pain relief
(5) Muscle relaxation

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What is premedication?

Combined drug treatment 1-3 Horus prior to anaesthesia

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What is the purpose of premedication?

(1) Reduce anxiety/ pain/ secretions/ vagal reflexes/ postoperative nausea + vomiting
(2) Increase amnesia/ hypnotic effects of anaesthesia

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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

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What is induction?

IV bolus agents

Induce loss of consciousness + amnesia

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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?

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