Mefenamic acid

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Mefenamic acid
Mefenamic acid2DACS.svg
Mefenamic acid3Dan.gif
Systematic (IUPAC) name
2-(2,3-dimethylphenyl)aminobenzoic acid
Clinical data
Trade names Ponstel, Ponstan
AHFS/Drugs.com monograph
MedlinePlus a681028
Pregnancy cat. C (AU) C (US)
Legal status Pharmacy Only (S2) (AU) POM (UK) ℞-only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 90%
Protein binding 90%
Metabolism Hepatic (CYP2C9)
Half-life 2 hours
Excretion Urine (66%), faeces (20-25%)
Identifiers
CAS number 61-68-7 YesY
ATC code M01AG01
PubChem CID 4044
IUPHAR ligand 2593
DrugBank DB00784
ChemSpider 3904 YesY
UNII 367589PJ2C YesY
KEGG D00151 YesY
ChEBI CHEBI:6717 N
ChEMBL CHEMBL686 YesY
Chemical data
Formula C15H15NO2 
Mol. mass 241.285 g/mol
 N (what is this?)  (verify)

Mefenamic acid is a non-steroidal anti-inflammatory drug used to treat pain, including menstrual pain. It is typically prescribed for oral administration. Mefenamic acid is marketed in the USA as Ponstel and is commonly known in UK as Ponstan.

Mefenamic acid decreases inflammation (swelling) and uterine contractions by a still-unknown mechanism. However it is thought to be related to the inhibition of prostaglandin synthesis. There is also evidence that supports the use of mefenamic acid for perimenstrual migraine headache prophylaxis, with treatment starting 2 days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the duration of menstruation.[1]

Since hepatic metabolism plays a significant role in mefenamic acid elimination, patients with known liver deficiency may be prescribed lower doses. Kidney deficiency may also cause accumulation of the drug and its metabolites in the excretory system. Therefore patients suffering from renal conditions should not be prescribed mefenamic acid.

Availability[edit]

Tablets 100 mg, 250 mg, 500 mg. Capsules: 250 mg. Suspension: 50 mg/5 ml [2]

Mechanism of action[edit]

Mefenamic acid is a competitive inhibitor of COX-1 and COX-2, which are responsible for the first committed step in prostaglandin biosynthesis.[3] Decreasing the activity of these enzymes thus reduces the production of prostaglandins, which are implicated in inflammation and pain processes.[4]

Pharmacokinetics[edit]

Absorption: Rapidly absorbed. Tmax is 2 to 4 h. Cmax is 20 µg/mL (single doses). Steady state is reached in 2 days.

Distribution: Apparent Vd is 1.06 L/kg. Protein binding is more than 90%. Excreted in breast milk.

Metabolism: Metabolized by CYP-450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acid (metabolite I). Further oxidation to a 3-carboxymefenamic acid (metabolite II) may occur. The metabolites may undergo glucuronidation, and mefenamic acid is also glucuronidated directly.

Elimination: Approximately 52% of a dose is excreted into the urine primarily as glucuronides of mefenamic acid (6%), 3-hydroxymefenamic acid (25%), and 3-carboxymefenamic acid (21%). The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid. The half-life is approximately 2 h. [5]

Adverse Reactions[edit]

Cardiovascular: CHF; hypertension; syncope; tachycardia. CNS: Dizziness, headache (up to 10%). Dermatologic: Pruritus, rashes (up to 10%). GI: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, nausea, vomiting (up to 10%). Hematologic: Anemia, increased bleeding time (up to 10%). Hepatic: Elevated liver enzymes (up to 10%). Miscellaneous: Abnormal renal function, edema, tinnitus (up to 10%) [6]

Side effects[edit]

Known mild side effects of mefenamic acid include headaches, nervousness and vomiting. Serious side effects may include diarrhea, hematemesis (vomiting blood), haematuria (blood in urine), blurred vision, skin rash, itching and swelling, sore throat and fever. It is advised to consult a doctor immediately if these symptoms appear while taking this medication.

Mefenamic acid is recommended to be taken with food.[7]

Overdose[edit]

Overdose can lead to a range of symptoms including convulsions, nausea, emesis, haematemesis, bradypnea, coma. Onset of symptoms is usually between 30 minutes and 4 hours, but signs of renal failure may appear several days after an overdose. Seek medical attention immediately in the case of overdose. The lethal dose can be as low as 2.5 g.

Synthesis[edit]

Analogous to fenamic acid, this compound may be synthesized from 2-chlorobenzoic acid and 2,3-dimethylaniline.[8]

Precautions[edit]

Mefenamic Acid cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. The pharmacological activity of Mefenamic Acid in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. Renal and hepatic impairment, asthma. Monitor blood counts and liver function during long-term therapy.[9]

Brand names[edit]

Beafemic, Mefalth, Mefalth T, Mefivan, Ponstel, Ponstan, Ponstal, Parkemed, Revalan, Mafepain, Mefamed, Mephadolor, Meftal, Dyfenamic, Potalon, Dolfenal, Meyerdonal, Alfoxan, Fenagesic, Fenamin, Spiralgin, Almus, Mefacit, Pangesic Forte, Kalmadol, Fespa,mefcox, Mefanorm (India).

References[edit]

  1. ^ Pringsheim, T.; Davenport, W. J.; Dodick, D. (2008). "Acute Treatment and Prevention of Menstrually Related Migraine Headache: Evidence-Based Review". Neurology 70 (17): 1555–1563. doi:10.1212/01.wnl.0000310638.54698.36. PMID 18427072. 
  2. ^ National formulary of India, 4th Ed. New Delhi, India, Indian Pharmacopoeia commission; 2011: 7
  3. ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720641/
  4. ^ http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0704092/abstract;jsessionid=62C075BC55DE8389CE3C56CBD0035181.d03t03
  5. ^ http://www.drugs.com/ppa/mefenamic-acid.html
  6. ^ http://www.drugs.com/ppa/mefenamic-acid.html
  7. ^ "Side effects for Mefenamic Acid". Medline Plus. National Institutes of Health. 
  8. ^ Trinus, F. P.; Mokhort, N. A.; Yagupol'skii, L. M.; Fadeicheva, A. G.; Danilenko, V. S.; Ryabukha, T. K.; Fialkov, Yu. A.; Kirichek, L. M.; Endel'man, É. S.; Get'man, G. A. (1977). "Mefenamic acid — A Nonsteroid Antiinflammatory Agent". Pharmaceutical Chemistry Journal 11 (12): 1706–1711. doi:10.1007/BF00778304. 
  9. ^ http://www.drugsupdate.com/generic/view/285

Sources[edit]