Anticholinesterases for Myasthenia Gravis


Neostigmine, Pyridostigmine 


  Issues for Surgery


Increase in muscle weakness, potentially including respiratory muscles, if omitted.

Interaction with neuromuscular blockers if continued (see Interaction(s) with Common Anaesthetic Agents).


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue.

Ensure Anaesthetist is aware of the drug interactions.

 

  Interaction(s) with Common Anaesthetic Agents


Local anaesthetics

Local or regional anaesthesia is often preferred in myasthenia gravis; however, the dose of ester local anaesthetics may need to be reduced due to concomitant pyridostigmine or neostigmine treatment1.

Neuromuscular Blocking Drugs (NMBDs)

Non-depolarising NMBDs
Patients with myasthenia gravis have a reduced number of acetylcholine receptors; this leads to high sensitivity to non-depolarising NMBDs and patients may only require 10% of a normal dose. Medium-acting drugs e.g. atracurium or vecuronium are preferred to long-acting drugs e.g. pancuronium and rocuronium but, even with dose reduction; the duration of the block can be prolonged1.

Pyridostigmine and neostigmine antagonise the effect of NMBDs and neostigmine is routinely used for reversal1, 2, 3. However, in patients with myasthenia gravis reversal can be unpredictable, partially due to chronic anticholinesterase treatment. Excessive administration of reversal agents could precipitate cholinergic crisis1, 4, 5.

Suxamethonium
Suxamethonium has decreased efficacy at usual doses in patients with myasthenia gravis due to a reduced number of acetylcholine receptors1. Higher doses or repeated doses of suxamethonium may produce a dual block (non-depolarising block following the initial depolarising block) resulting in delayed recovery6.

Unlike non-depolarising NMBDs, administration of pyridostigmine or neostigmine increases the concentration of acetylcholine at the neuromuscular junction and thus prolongs the action of suxamethonium 1, 4, 5. Ideally suxamethonium should be avoided in patients with myasthenia gravis.

Bradycardia

Pyridostigmine and neostigmine can increase the risk of bradycardia when used concomitantly with the following6: -

  • alfentanil, fentanyl or remifentanil
  • cisatracurium


  Interaction(s) with other Common Medicines used in the Perioperative Period


Aminoglycoside antibiotics (e.g. amikacin, gentamicin, neomycin, streptomycin, tobramycin) are contraindicated in patients with myasthenia gravis as they impair neuromuscular transmission6.


  Further Information


The stress of surgery and potential exposure to exacerbating drugs can trigger a myasthenia crisis5.


  References


  1. Brambrink, A. & Kirsch, J. Perioperative Care of Patients with Neuromuscular Disease and Dysfunction. Anesthesiology Clinics. 2007; 25(3): 483-509
  2. Summary of Product Characteristics – Neostigmine Bromide Tablets15mg. Alliance pharmaceuticals. Accessed via www.medicines.org.uk 10/05/2019 [date of revision of the text February 2015]
  3. Summary of Product Characteristics – Mestinon® (pyridostigmine). Mylan products limited. Accessed via www.medicines.org.uk 10/05/2019 [date of revision of the text February 2018]
  4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10th May 2019]
  5. Myaware (registered charity 1046443). http://www.myaware.org [Accessed on 10th May 2019]
  6. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10th May 2019]