Pyridostigmine - Misplaced Pages

(Redirected from Pyridostigmine bromide) Medication used to treat myasthenia gravis Not to be confused with Physostigmine. Pharmaceutical compound

Pyridostigmine
Clinical data


Trade names	Mestinon, others
AHFS/Drugs.com	Monograph
MedlinePlus	a682229
Pregnancy category	AU: C
Routes of administration	By mouth, intravenous
Drug class	Acetylcholinesterase inhibitor; Parasympathomimetic
ATC code	N07AA02 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	7.6 ± 2.4%
Elimination half-life	1.78 ± 0.24 hours
Excretion	kidney
Identifiers
IUPAC name 3--1-methylpyridinium
CAS Number	155-97-5
PubChem CID	4991
DrugBank	DB00545
ChemSpider	4817
UNII	19QM69HH21
KEGG	C07410
ChEMBL	ChEMBL1115
CompTox Dashboard (EPA)	DTXSID20165786
Chemical and physical data
Formula	C₉H₁₃N₂O₂
Molar mass	181.215 g·mol
3D model (JSmol)	Interactive image
SMILES O=C(Oc1ccc(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 Key:RVOLLAQWKVFTGE-UHFFFAOYSA-N
(verify)

Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is also used off-label to treat some forms of Postural orthostatic tachycardia syndrome. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 4 hours.

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 fetus. 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.

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

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.

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

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

It is also being prescribed off-label for postural orthostatic tachycardia syndrome (POTS) as well as complications resulting from Ehlers–Danlos syndrome.

Contraindications

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

Side effects

Common side effects include:

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:

Muscle twitching
Muscle cramps and weakness

Mechanism of action

Pyridostigmine is an acetylcholinesterase inhibitor. It 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 name Mestinon (Valeant Pharmaceuticals), Regonol and Gravitor (SUN Pharma).

References

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.
Moro C, Phelps C, Veer V, Clark J, Glasziou P, Tikkinen KA, Scott AM (November 2021). "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics. 41 (1): 127–139. doi:10.1002/nau.24839. PMID 34816481. S2CID 244530010.
^ "Neostigmine Bromide". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 540. ISBN 9783527607495. Archived from the original on 2016-12-20.
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.
"Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Retrieved 6 March 2023.
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): 4295–4300. Bibcode:2008PNAS..105.4295G. doi:10.1073/pnas.0711986105. JSTOR 25461411. PMC 2393741. PMID 18332428.
Steenhuysen, Julie (March 10, 2008). "Gulf War illness linked to chemical exposure-study". Reuters.
Moro C, Phelps C, Veer V, Clark J, Glasziou P, Tikkinen KA, Scott AM (November 2021). "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics. 41 (1): 127–139. doi:10.1002/nau.24839. PMID 34816481. S2CID 244530010.
Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy. 41 (2): 314–318. doi:10.1345/aph.1H458. PMID 17284509. S2CID 22855759.
^ Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy. 41 (2): 314–318. doi:10.1345/aph.1H458. PMID 17284509. S2CID 22855759.
Kanjwal K, Karabin B, Sheikh M, Elmer L, Kanjwal Y, Saeed B, Grubb BP (June 2011). "Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience". Pacing and Clinical Electrophysiology. 34 (6): 750–755. doi:10.1111/j.1540-8159.2011.03047.x. PMID 21410722. S2CID 20405336.
^ Mestinon | Home Archived 2008-05-13 at the Wayback Machine
Mestinon Official FDA information, side effects and uses Archived 2008-05-24 at the Wayback Machine