Q11

Describe the mechanism of action of lignocaine on the heart

  • Na channel blockade

Describe the adverse effects of lignocaine

  • Stepwise CNS effects
  • Cardiovascular Na blockade

Q12

What is drug biotransformation?

  • Drug metabolism to allow drugs to become inactive or by increasing excretion by making them more hydrophilic, or by metabolising them to less active agent.

Pass Criteria:

  • Bold to pass

Describe phase 1 and phase 2 reactions.

  • Phase 1
    • Unmasking functional group (-OH, -NH2, -SH) to become more polar metabolite
    • Includes oxidation, deamination, hydrolysis, reductions
  • Phase 2
    • Conjugation with endogenous substrate to become highly polar conjugate

Pass Criteria:

  • Bold to pass

How is suxamethonium metabolised?

  • Rapid phase 1 hydrolysis by butyrycholinesterase and pseudocholinesterase in liver and plasma

Pass Criteria:

  • One of bold to pass

Why may a patient have a prolonged paralysis following Suxamethonium?

  • Genetically deficient in BCHE so slowed metabolism

Q13

You decide to use Bupivicaine as the local anaesthetic to insert a chest tube. What is the mechanism of action of bupivacaine?

  • Blocks voltage-gated sodium channels in nerve
  • Threshold for excitation increases, conduction slows, action potential rise declines, action potential generation abolished
  • If sodium current blocked over length of nerve, propagation is ceased

Pass Criteria:

  • Bold to pass

How long will a bupivacaine block last?

  • 3-6 hours

Pass Criteria:

  • Approximate or long duration

What are the potential adverse effects from bupivacaine?

  • CNS toxicity
    • Sedation
    • Light headedness
    • Visual & auditory
    • Tongue & mouth numbness
    • Metallic taste
    • Nystagmus
    • Restlessness
    • Muscle twitches
    • Seizure
    • Respiratory depression
  • Cardiac toxicity
    • Arrhythmias
    • Cardiovascular collapse
    • Cardiac arrest
  • Local toxicity
    • Trauma
    • Neurotoxicity
  • Allergy

Pass Criteria:

  • Bold to pass

How can the risk of these effects be minimised in the ED?

  • Ask re history of allergy
  • Use safe maximum dose (<2mg/kg)
  • Withdraw pre-injection
  • Avoid vessels – anatomical consideration (above rib below) and use USS
  • Ask patient to flag symptoms e.g. taste/tongue numb
  • Avoid hypoxia/acidosis

Q14

What is suxamethonium?

  • Depolarising muscle relaxant producing rapid neuromuscular blockade at motor endplate nicotinic receptors.
  • Structurally two acetylcholine molecules linked end to end

Pass Criteria:

  • Bold to pass

Describe the mechanism of action of suxamethonium.

  • Phase 1 (depolarising)
    • Binds to nicotinic receptor
    • Opens channel and causes depolarisation of motor end plate
    • Spread to adjacent membranes causing contractions of muscle motor units (fasciculations)
    • Depolarised membranes remain depolarised (& unresponsive to subsequent impulses) causing flaccid paralysis
  • Phase 2 (desensitising)
    • With continued exposure, the initial end plate depolarisation decreases & membrane becomes repolarised
    • Membrane cannot be depolarised again as it is desensitised (mechanism unclear however ? due to channel block becoming more important thanagonist action at receptor)

Pass Criteria:

  • Bold to pass

What are the important adverse effects of suxamethonium?

  • Hyperkalaemia (e.g. burns, trauma patient)
  • Cardiac arrhythmias (e.g. if given with halothane)/bradycardia (repeat doses)
  • Increased IOP
  • Increased intragastric pressure
  • Muscle pain (likely related to fasciculation)
  • Malignant hyperthermia
  • Prolonged paralysis

Pass Criteria:

  • 2 bold and 2 others to pass

Q15

Describe the pharmacokinetics of propofol.

  • Distribution half life 2-4 minutes
  • Elimination half life 4-23 minutes
  • Rapid onset and recovery
  • Termination of drug effect due to redistribution from brain to skeletal muscle and then fat (rather than metabolism)
  • Duration of action 3-8 minutes
  • Rapidly metabolised in liver and extrahepatic sites (lungs)
  • Water soluble metabolites excreted in urine

Pass Criteria:

  • Bold to pass

What is the usual induction dose of propofol?

  • 1-2.5mg/kg adults
  • 2.5-3.5mg/kg in kids

Pass Criteria:

  • Bold to pass

What clinical effects are expected after this dose of propofol is administered?

  • Anaesthesia/Sedation
  • Respiratory depression
  • Transient apnoea
  • Decreased blood pressure through vaso and venodilation (most pronounced of induction drugs)
  • Does NOT have analgesic properties
  • Anti-emesis
  • Metabolic acidosis
  • Pain at injection site

Pass Criteria:

  • Bold to pass

List some drug interactions of propofol important in the setting of sedation/anaesthesia.

  • Opioids – enhance respiratory depression
  • Benzodiazepines – enhanced sedation and respiratory depression

Pass Criteria:

  • 1 of 2

Q16

Describe the mechanism of action of lignocaine.

  • Sodium channel blocker, Class 1B
  • Blocks (activated and inactivated) sodium channels = Blocks nerve conduction.
  • Less effect in infected tissue

Pass Criteria:

  • Bold to pass

What factors affect systemic absorption after local infiltration?

  • Dose
  • Site of injection
  • Drug tissue binding
  • Tissue blood flow
  • Vasoconstrictors (combined preparation)

Pass Criteria:

  • 3/5

What are the toxic effects of lignocaine?

  • CNS
    • Early
      • Tongue/oral numbness/metallic taste
      • Paraesthesia
      • Sedation
    • Moderate
      • Nystagmus
      • Muscle twitching
      • Nausea/vomiting
      • Tinnitus
      • Visual disturbance
    • Severe
      • Seizures
      • Sedation
  • CVS
    • Cardiovascular collapse
    • Hypotension
    • Bradycardia
    • Rarely arrhythmia, worsen CCF or conduction blocks
  • GIT
    • Anorexia
    • Nausea/vomiting (through CNS effects)

Pass Criteria:

  • Bold to pass

 


Q17

Please outline the pharmacokinetics of propofol.

  • IV administration only
  • Distribution half life 2-4 minutes
  • Elimination half life 4-23 minutes
  • Duration of action 3-8 minutes
  • Rapid onset and recovery due to redistribution of drug from brain to skeletal muscle and then fat (rather than metabolism)
  • Rapidly metabolised in the liver but as total body plasma clearance > hepatic flow, likely some extrahepatic mechanism (mostly lung)
  • Excretion in the urine as glucuronides and sulphates <1% unchanged

Pass Criteria:

  • Bold to pass
  • Reasonable understanding of redistribution of drug

What does of propofol is used for induction of general anaesthesia? How does this differ from a procedural sedation dose.

  • Procedural sedation dose: 0.5 – 1.0 mg/kg single bolus dose or titrate in 10-20mg aliquots particularly in conjunction with morphine.
  • Induction dose: 1 – 2.5 mg/kg (adults) and 2.5 – 3.5 mg/kg (kids)

Pass Criteria:

  • Bold to pass

What clinical effects should be anticipated when using propofol?

  • Anaesthesia/sedation
  • Respiratory depression
  • Transient apnoea
  • Hypotension through vaso and veno dilation
  • No analgesic properties
  • Potential allergic reaction (soy, eggs)
  • Pain at injection site
  • Metabolic acidosis when given as an infusion
  • Antiemetic properties

Pass Criteria:

  • Bold + 2 more

How can you limit adverse effects when administering propofol?

  • Smaller total doses
  • Titrated doses
  • No opiates or benzodiazepines given simultaneously
  • IV fluid bolus
  • Caution in the elderly and those with poor cardiovascular reserve

Pass Criteria:

  • 2 to pass

Q18

What is the mechanism of vecuronium

  • Non depolarising neuromuscular blockade
  • Competitive antagonist for acetylcholine at nicotinic receptors of neuromuscular junction
  • Large doses will enter ion channel’s pore directly –> more intense blockade
  • Also blocks prejunctional Na channels –> interfere with Ach mobilization at nerved endings

Pass Criteria:

  • Must mention blockade type & either receptor type or Ach

Describe the pharmokinetics of vecuronium.
Prompt: What is its onset time, what is its duration of action, how is it eliminated?

  • Highly polar/ionic
  • Poorly absorbed from GIT
  • Given IV
  • Onset within 1 min
  • Max effect at 3-5 mins
  • Duration of action 20-35 mins
  • Short half life
  • Rapidly distributed to extracellular space
  • Small volume of distribution (~blood vol)
  • Plasma protein binding: 60-90%
  • Eliminated by liver (75-90%) rest by kidney

Pass Criteria:

  • 4 of 6 Bold to pass

Q19

What is the mechanism of action of suxamethonium?

Depolarising neuromuscular blocker

  • Phase 1 (depolarising)
    • Binds to nicotinic receptor
    • Opens channel and causes depolarisation of motor end plate
    • Spread to adjacent membranes causing contractions of muscle motor units (fasciculations)
    • Depolarised membranes remain depolarised (& unresponsive to subsequent impulses) causing flaccid paralysis
  • Phase 2 (desensitising)
    • With continued exposure, the initial end plate depolarisation decreases & membrane becomes repolarised
    • Membrane cannot be depolarised again as it is desensitised (mechanism unclear however ? due to channel block becoming more important thanagonist action at receptor)

Pass Criteria:

  • Bold and understanding of concept to pass

What are the pharmacokinetic properties of suxamethonium?

  • Rapid onset (30 – 60 seconds)
  • Short duration of action (2 – 8 minutes)
  • Hydrolised rapidly by plasma cholinesterase

Pass Criteria:

  • 2 of 3 bold to pass.

What are the important adverse effects of suxamethonium?

  • Hyperkalaemia (e.g. burns, trauma patient)
  • Cardiac arrhythmias (e.g. if given with halothane)/bradycardia (repeat doses)
  • Increased IOP
  • Increased intragastric pressure
  • Muscle pain (likely related to fasciculation)
  • Malignant hyperthermia
  • Prolonged paralysis

Pass Criteria:

  • 4 of 7 to pass.

 


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