21A06: Exam Report

Describe the pharmacology of vecuronium, including factors that prolong its action of neuromuscular blockade.

13% of candidates passed this question.

Vecuronium is a commonly available and regularly used amino-steroid neuromuscular blocking agent. It is a level 1 drug in the 2017 syllabus. A simple template utilising the headings; pharmaceutics, PK, PD, uses in ICU and adverse reactions with associated relevant important facts would have scored well. Expected information regarding the factors prolonging neuromuscular blockade included electrolyte abnormalities, drug interactions and patient factors. Overall, the level of understanding and knowledge demonstrated in the answers was below an expected standard for a level 1 drug.

L2i / 21A06: Describe the pharmacology of vecuronium, including factors that prolong its action of neuromuscular blockade

Tips

  • Always use a pharmaceutics/kinetics/dynamics structure for drug questions
  • Have a mental mnemonic for what to include in each section
  • The order of sections doesn’t matter – do what feels more natural to you or the stuff where you know more/think more marks will be allocated. But don’t use up all your time on one section → try and put something down for each section

I often include drug class in the opening statement, and uses if there aren’t many –  ie ‘Paracetamol is an acetanilide derivative used as an analgesic and antipyretic’ otherwise if there are heaps of uses make it a heading in itself. You could decide to be more specific about which patients you might use vec for here but I think time better spent in the prolonging factors list 

Definition

Vecuronium is an aminosteroid non-depolarising neuromuscular blocking drug used in the induction of anaesthesia and neuromuscular blockade in ICU.

Pharmaceutics

  • 10mg powder for reconstitution with 5ml water (the only one that is a powder – not great if you’re in a hurry)

Pharmacodynamics

  • MOA: Competitive nicotinic antagonist
    • Needs 75% receptor occupancy for effect
  • Effects:
    • Causes flaccid paralysis, reduced TOF count and ratio, reduced single twitch height
  • Dose
    • ED95 0.05mg/kg → intubating dose 0.1mg/kg
    • Maintenance bolus dose 0.02-0.03mg/kg
  • Antagonism/reversal
    • Yes → sugammadex or neostigmine + glycopyrrolate

Pharmacokinetics

  • A: Onset 90-120s, maximal effect 3-5mins
  • D: 60-90% protein binding, Vd 220ml/kg (all the NMBAs are around 150-250ml/kg)
  • M: hepatic deacetylation ot active metabolites
  • E: duration 25-40mins, 70% excretion in bile (20% unchanged + active metabolites), 30% excretion in urine

Adverse Effects

  • Slight CO increase and SVR decrease at larger doses
  • Rare histamine release (→ hypotension, allergy, anaphylaxis)

Factors that prolong duration of action

Try and remember the electrolytes as it comes up a fair bit. Renal and hepatic failure are easy marks. Drug interactions mechanisms less important but drugs and their direction worth rote learning.

  • Recovery = return to 25% baseline twitch height or recovery of TOFR >0.9
  • Patient factors
    • Electrolytes
      • hypoK – potentiates non-depolarising NMBA, prevents depolarisation
      • hypoCa – decreased Ach release
      • hyperMg – potentiates blockage – decreased Ach release and sensitivity of post-synaptic membrane
    • Age – older = longer
    • Sex
    • Muscle mass
    • Temperature
    • Acidosis
    • NMJ disorder eg MG
    • Hepatic disease – prolonged elimination of active metabolites to longer half life
    • Renal disease – prolonged elimination of active metabolites to longer half life
  • Drug interactions
    • Volatile anaesthetics – increased Ach affinity at nicotinic R and block positive feedback at pre-synaptic receptors
    • Gentamicin – block pre-synaptic Ca channels -> decreased Ach release
    • LA – block post-synaptic Na channels – muscle fibre depression
    • Lithium – decreased membrane excitability
    • Ca blockers – decreased pre-synaptic Ach release

Tips

→ in general for NMBAs, have lists for (and expect for future sittings):

  • Factors affecting speed of onset (patient/drug/interactions)
  • Factors affecting duration of action (same structure)
  • Factors potentiating effect (same structure or PD/PK/pceutic)

Author: Manon Audigé