Diflunisal

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Diflunisal
Diflunisal structure.svg
Systematic (IUPAC) name
2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid
Clinical data
AHFS/Drugs.commonograph
MedlinePlusa684037
Pregnancy cat.C (AU) C (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral
Pharmacokinetic data
Bioavailability80-90%
Protein binding>99%
MetabolismHepatic
Half-life8 to 12 hours
ExcretionRenal
Identifiers
CAS number22494-42-4 YesY
ATC codeN02BA11
PubChemCID 3059
DrugBankDB00861
ChemSpider2951 YesY
UNII7C546U4DEN YesY
KEGGD00130 YesY
ChEBICHEBI:39669 YesY
ChEMBLCHEMBL898 YesY
PDB ligand ID1FL (PDBe, RCSB PDB)
Chemical data
FormulaC13H8F2O3 
Mol. mass250.198 g/mol
 YesY (what is this?)  (verify)
 
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Diflunisal
Diflunisal structure.svg
Systematic (IUPAC) name
2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid
Clinical data
AHFS/Drugs.commonograph
MedlinePlusa684037
Pregnancy cat.C (AU) C (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral
Pharmacokinetic data
Bioavailability80-90%
Protein binding>99%
MetabolismHepatic
Half-life8 to 12 hours
ExcretionRenal
Identifiers
CAS number22494-42-4 YesY
ATC codeN02BA11
PubChemCID 3059
DrugBankDB00861
ChemSpider2951 YesY
UNII7C546U4DEN YesY
KEGGD00130 YesY
ChEBICHEBI:39669 YesY
ChEMBLCHEMBL898 YesY
PDB ligand ID1FL (PDBe, RCSB PDB)
Chemical data
FormulaC13H8F2O3 
Mol. mass250.198 g/mol
 YesY (what is this?)  (verify)

Diflunisal is a non-steroidal anti-inflammatory drug (NSAID). It was developed by Merck Sharp & Dohme in 1971 after showing promise in a research project studying more potent chemical analogs of aspirin.[1] It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is available in 250 mg and 500 mg tablets. As of 2013, the drug was in clinical trials as a potential treatment for transthyretin-related hereditary amyloidosis.

Mechanism of Action[edit]

Like all NSAIDs, diflunisal acts by inhibiting the production of prostaglandins,[2] hormones which are involved in inflammation and pain. Diflunisal also has an antipyretic effect, but this is not a recommended use of the drug. Though diflunisal has an onset time of 1 hour, and maximum analgesia at 2 to 3 hours, the plasma levels of diflunisal will not be steady until repeated doses are taken.[citation needed] The long plasma half-life is a distinctive feature of diflunisal in comparison to similar drugs. To increase the rate at which the diflunisal plasma levels become steady, a loading dose is usually used. It is primarily used to treat symptoms of arthritis, and for acute pain following oral surgery, especially removal of wisdom teeth.

Effectiveness of diflunisal is similar to other NSAIDs, but the duration of action is twelve hours or more.[3] This means fewer doses per day are required for chronic administration. In acute use, it is popular in dentistry when a single dose after oral surgery can maintain analgesia until the patient is asleep that night.

Medical Uses[edit]

Side Effects[edit]

Gastrointestinal[edit]

The inhibition of prostaglandins has the effect of decreasing the protection given to the stomach from its own acid. Like all NSAIDS, this leads to an increased risk of stomach ulcers, and their complications, with long-term use. Elderly users of diflunisal are at greater risk for serious GI events.

Cardiovascular[edit]

Ear, nose, throat, and eye[edit]

Central nervous system[edit]

Skin[edit]

Contraindications[edit]

Cautions[edit]

Overdose[edit]

Deaths that have occurred from diflunisal usually involved mixed drugs and or extremely high dosage. The oral LD50 is 500 mg/kg. Symptoms of overdose include coma, tachycardia, stupor, and vomiting. The lowest dose without the presence of other medicines which caused death was 15 grams. Mixed with other medicines, a death at 7.5 grams has also occurred. Diflunisal usually comes in 250 or 500 mg, making it relatively hard to overdose by accident.

References[edit]

  1. ^ Adams, S. S. (1999). "Ibuprofen, the propionics and NSAIDs: Personal reflections over four decades". Inflammopharmacology 7 (3): 191–197. doi:10.1007/s10787-999-0002-3. PMID 17638090.  edit
  2. ^ Wallace, J. L. (2008). "Prostaglandins, NSAIDs, and Gastric Mucosal Protection: Why Doesn't the Stomach Digest Itself?". Physiological Reviews 88 (4): 1547–1565. doi:10.1152/physrev.00004.2008. PMID 18923189.  edit
  3. ^ http://www2.cochrane.org/reviews/en/ab007440.html

External links[edit]