Pyridostigmine

Not to be confused with Physostigmine.
Pyridostigmine
Names
Trade namesMestinon, others
IUPAC name
  • 3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Drug classAcetylcholinesterase inhibitor (cholinergic)[1]
Main usesMyasthenia gravis[2]
Side effectsNausea, diarrhea, frequent urination, abdominal pain[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		by mouth, intravenous
    Defined daily dose0.18 gram (by mouth)
    10 mg (by injection)[3]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa682229
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability7.6 +/- 2.4%
    Elimination half-life1.78 +/- 0.24hrs
    Excretionkidney
    Chemical and physical data
    FormulaC9H13N2O2
    Molar mass181.215 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C(Oc1ccc[n+](c1)C)N(C)C
    InChI
    • InChI=1S/C9H13N2O2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7H,1-3H3/q+1 checkY
    • Key:RVOLLAQWKVFTGE-UHFFFAOYSA-N checkY

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

    Common side effects include nausea, diarrhea, frequent urination, and abdominal pain.[1] More severe side effects include low blood pressure, weakness, and allergic reactions.[1] It is unclear if use in pregnancy is safe for the baby.[1] Pyridostigmine is an acetylcholinesterase inhibitor in the cholinergic family of medications.[1] It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.[1]

    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.[1] The wholesale cost in the developing world is about US$7.17–65.93 a month.[6] In the United States it costs about US$25–50 per month.[7]

    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.[8]

    Pyridostigmine sometimes is used to treat orthostatic hypotension.[9] It may also be of benefit in chronic axonal polyneuropathy.[10]

    It is also being prescribed 'off-label' for the postural tachycardia syndrome as well as complications resulting from Ehlers–Danlos syndrome.[10][11]

    Dosage

    The defined daily dose is 0.18 gram (by mouth) or 10 mg (by injection).[3]

    Contraindications

    Pyridostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma.[12][13]

    Side effects

    Common side effects include:[12]

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

    Mechanism of action

    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.

    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.

    Names

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

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 "Neostigmine Bromide". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
    2. 1 2 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 429. hdl:10665/44053. ISBN 9789241547659.
    3. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 6 August 2020. Retrieved 19 September 2020.
    4. ↑ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 540. ISBN 9783527607495. Archived from the original on 2016-12-20.
    5. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    6. ↑ "Pyridostigmine Bromide". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
    7. ↑ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 339. ISBN 9781284057560.
    8. ↑ 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 2393741. PMID 18332428.
    9. ↑ 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.
    10. 1 2 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.
    11. ↑ 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.
    12. 1 2 Mestinon | Home Mestinon® at the Wayback Machine (archived 2008-05-13)(Positional parameters ignored)
    13. ↑ Mestinon Official FDA information, side effects and uses Mestinon Official FDA information, side effects and uses. at the Wayback Machine (archived 2008-05-24)
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