Chemistry:Pyridostigmine

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Short description: Medication used to treat myasthenia gravis and chronic Orthostatic Hypotension
Pyridostigmine
Pyridostigmine.svg
Pyridostigmine ball-and-stick.png
Clinical data
Trade namesMestinon, others
AHFS/Drugs.comMonograph
MedlinePlusa682229
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability7.6 +/- 2.4%
Elimination half-life1.78 +/- 0.24hrs
Excretionkidney
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC9H13N2O2
Molar mass181.215 g·mol−1
3D model (JSmol)
  (verify)

Pyridostigmine is a medication used to treat myasthenia gravis[1] and underactive bladder.[2] It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type.[3] It is typically given by mouth but can also be used by injection.[3] The effects generally begin within 45 minutes and last up to 6 hours.[3]

Common side effects include nausea, diarrhea, frequent urination, and abdominal pain.[3] More severe side effects include low blood pressure, weakness, and allergic reactions.[3] It is unclear if use in pregnancy is safe for the fetus.[3] Pyridostigmine is an acetylcholinesterase inhibitor in the cholinergic family of medications.[3] It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.[3]

Pyridostigmine was patented in 1945 and came into medical use in 1955.[4] It is on the World Health Organization's List of Essential Medicines.[5] Pyridostigmine is available as a generic medication.[3][6]

Medical uses

Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis or forms of congenital myasthenic syndrome and to combat the effects of curariform drug toxicity. Pyridostigmine bromide has been FDA approved for military use during combat situations as an agent to be given prior to exposure to the nerve agent Soman in order to increase survival. Used in particular during the first Gulf War, pyridostigmine bromide has been implicated as a causal factor in Gulf War syndrome.[7][8]

With pyridostigmine classified as a type of parasympathomimetic, it can be used to treat underactive bladder.[9]

Pyridostigmine sometimes is used to treat orthostatic hypotension.[10] It may also be of benefit in chronic axonal polyneuropathy.[11]

It is also being prescribed 'off-label' for postural orthostatic tachycardia syndrome as well as complications resulting from Ehlers–Danlos syndrome.[11][12]

Contraindications

Pyridostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma.[13][14]

Side effects

Common side effects include:[13]

  • Sweating
  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal cramps
  • Increased salivation
  • Tearing
  • Increased bronchial secretions
  • Constricted pupils
  • Facial flushing due to vasodilation
  • Erectile dysfunction

Additional side effects include:[13]

  • Muscle twitching
  • Muscle cramps and weakness

Mechanism of action

Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the hydrolysis of acetylcholine. Like its predecessor neostigmine, it is a quaternary carbamate inhibitor of cholinesterase that does not cross the blood–brain barrier. It carbamylates about 30% of peripheral cholinesterase enzyme, and the carbamylated enzyme eventually regenerates by natural hydrolysis and excess acetylcholine (ACh) levels revert to normal.

The ACh diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing an influx of sodium (Na+,) resulting in depolarization. If large enough, this depolarization results in an action potential. To prevent constant stimulation once the ACh is released, an enzyme called acetylcholinesterase is present in the endplate membrane close to the receptors on the post synaptic membrane, and quickly hydrolyses ACh.

Names

Pyridostigmine bromide is available under the trade names Mestinon (Valeant Pharmaceuticals), Regonol and Gravitor (SUN Pharma).

References

  1. ↑ WHO Model Formulary 2008. World Health Organization. 2009. p. 429. ISBN 9789241547659. 
  2. ↑ "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics 41 (1): 127–139. November 2021. doi:10.1002/nau.24839. PMID 34816481. https://research.bond.edu.au/en/publications/62295e6a-d035-4557-bb8d-12380be96c0c. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "Neostigmine Bromide". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/neostigmine-bromide.html. 
  4. ↑ (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 540. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA540. 
  5. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  6. ↑ "Competitive Generic Therapy Approvals". 3 March 2023. https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals. 
  7. ↑ "Acetylcholinesterase inhibitors and Gulf War illnesses". Proceedings of the National Academy of Sciences of the United States of America 105 (11): 4295–4300. March 2008. doi:10.1073/pnas.0711986105. PMID 18332428. Bibcode: 2008PNAS..105.4295G. 
  8. ↑ Steenhuysen, Julie (March 10, 2008). "Gulf War illness linked to chemical exposure-study". Reuters. https://www.reuters.com/article/idUSN10593482. 
  9. ↑ "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics 41 (1): 127–139. November 2021. doi:10.1002/nau.24839. PMID 34816481. https://research.bond.edu.au/en/publications/62295e6a-d035-4557-bb8d-12380be96c0c. 
  10. ↑ "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–318. February 2007. doi:10.1345/aph.1H458. PMID 17284509. 
  11. ↑ 11.0 11.1 "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–318. February 2007. doi:10.1345/aph.1H458. PMID 17284509. 
  12. ↑ "Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience". Pacing and Clinical Electrophysiology 34 (6): 750–755. June 2011. doi:10.1111/j.1540-8159.2011.03047.x. PMID 21410722. 
  13. ↑ 13.0 13.1 13.2 Mestinon | Home
  14. ↑ Mestinon Official FDA information, side effects and uses

External links



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