Pyridostigmine

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Pyridostigmine
Pyridostigmine.svg
Pyridostigmine ball-and-stick.png
Clinical data
Trade names Mestinon, others
AHFS/Drugs.com Monograph
MedlinePlus a682229
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration
by mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 7.6 +/- 2.4%
Biological half-life 1.78 +/- 0.24hrs
Excretion kidney
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C9H13N2O2
Molar mass 181.212 g/mol
3D model (Jmol)
  (verify)

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

Common side effects include nausea, diarrhea, frequent urination, and abdominal pain. More severe side effects include low blood pressure, weakness, and allergic reactions. It is unclear if use in pregnancy is safe for the baby. Pyridostigmine is an acetylcholinesterase inhibitor in the cholinergic family of medications. It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.[2]

Pyridostigmine was patented in 1945 and came into medical use in 1955.[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] Pyridostigmine is available as a generic medication.[2] The wholesale cost in the developing world is about 7.17 to 65.93 USD a month.[5] In the United States it costs about 25 to 50 USD per month.[6]

Medical uses[edit]

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]

Pyridostigmine sometimes is used to treat orthostatic hypotension.[8] It may also be of benefit in chronic axonal polyneuropathy.[9]

It is also being prescribed 'off-label' for the postural tachycardia syndrome as well as complications resulting from Ehlers–Danlos syndrome.[9][10]

Contraindications[edit]

Pyridostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma.[11][12]

Side effects[edit]

Common side effects include:[11]

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

Mechanism of action[edit]

In a synapse, action potentials are conducted along motor nerves to their terminals where they initiate a Ca2+ influx and the release of acetylcholine (ACh). The ACh diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing an influx of 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.

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

Names[edit]

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

References[edit]

  1. ^ WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 429. ISBN 9789241547659. Retrieved 8 December 2016. 
  2. ^ a b c "Neostigmine Bromide". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  3. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 540. ISBN 9783527607495. 
  4. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  5. ^ "Pyridostigmine Bromide". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  6. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 339. ISBN 9781284057560. 
  7. ^ Golomb BA (March 2008). "Acetylcholinesterase inhibitors and Gulf War illnesses". Proceedings of the National Academy of Sciences of the United States of America. 105 (11): 4295–300. Bibcode:2008PNAS..105.4295G. doi:10.1073/pnas.0711986105. JSTOR 25461411. PMC 2393741Freely accessible. PMID 18332428. Lay summaryReuters (March 10, 2008). 
  8. ^ Gales BJ, Gales MA (2007). "Pyridostigmine in the treatment of orthostatic intolerance". Annals of Pharmacotherapy. 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509. 
  9. ^ a b Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy. 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509. 
  10. ^ Kanjwal K, Karabin B, Sheikh M, et al. (June 2011). "Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience". Pacing and Clinical Electrophysiology. 34 (6): 750–5. doi:10.1111/j.1540-8159.2011.03047.x. PMID 21410722. 
  11. ^ a b Mestinon | Home
  12. ^ Mestinon Official FDA information, side effects and uses