- Diflunisal
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Diflunisal 
Systematic (IUPAC) name 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid Clinical data AHFS/Drugs.com monograph MedlinePlus a684037 Pregnancy cat. C(AU) C(US) Legal status POM (UK) ℞-only (US) Routes Oral Pharmacokinetic data Bioavailability 80-90% Protein binding >99% Metabolism Hepatic Half-life 8 to 12 hours Excretion Renal Identifiers CAS number 22494-42-4 
ATC code N02BA11 PubChem CID 3059 DrugBank APRD00922 ChemSpider 2951 UNII 7C546U4DEN KEGG D00130 ChEBI CHEBI:39669 ChEMBL CHEMBL898 Chemical data Formula C13H8F2O3 Mol. mass 250.198 g/mol SMILES eMolecules & PubChem - InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)
Key:HUPFGZXOMWLGNK-UHFFFAOYSA-N
(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.
Contents
Mechanism
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.
Side effects
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.
Gastrointestinal
- Increased risk of GI events including bleeding, ulceration, and stomach or intestine perforation. Elderly are at greater risk for serious GI events.
- Abdominal pain or cramps
- Constipation
- Gas
- Diarrhea
- Nausea and vomiting
- Dyspepsia
Cardiovascular
- Irregular heart beat
- This medication may increase risk of serious and potentially fatal cardiovascular thrombotic events, MI, and stroke
- Risk may increase with duration of use
- Increased risk for Cardiovascular disease history
- Contraindicated for Heart Bypass peri-op pain
Ear, nose, throat, and eye
- Ringing in the ears
- Yellowing of eyes
Central nervous system
- Drowsiness
- Dizziness
- Headache
- Insomnia
- Fatigue
- Somnolence
- Nervousness
Skin
- Swelling of the feet, ankles, lower legs, and hands
- Yellowing of skin
- Rash
- Ecchymosis
Overdose
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 is relatively hard to overdose by accident.
Indications
- Pain, mild to moderate
- Osteoarthritis
- Rheumatoid arthritis
- Injury to tendons
- Inflammation
- ATTR amyloidosis (harrison 17ed page 2148)
Contraindications
- Hypersensitivity to aspirin/NSAID-induced asthma or urticaria
- Aspirin triad
- 3rd trimester pregnancy
- CABG surgery (peri-op pain)
Cautions
- Cardiovascular diseases
- Cardiac risk factors
- Hypertension
- Congestive heart failure
- Elderly or debilitated
- Impaired liver function
- Impaired kidney function
- Dehydration
- Fluid retention
- History of gastrointestinal bleeds/PUD
- Asthma
- Coagulopathy
- Smoker
- Corticosteriod use
- Anticoagulant use
- Alcohol use
- Diuretic use
- ACE inhibitor use
References
- ^ 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.
- ^ Wallace, J. L. (2008). "Prostaglandins, NSAIDs, and Gastric Mucosal Protection: Why Doesn't the Stomach Digest Itself?". Physiological Reviews 88 (4): 1547. doi:10.1152/physrev.00004.2008. PMID 18923189. http://physrev.physiology.org/content/88/4/1547.full.
- ^ http://www2.cochrane.org/reviews/en/ab007440.html
External links
- Diflunisal: MedlinePlus Drug Information
- Dolobid Prescribing Information (manufacturer's website)
- Dolobid Medication Guide (manufacturer's website)
- Diflunisal (patient information)
- "Single dose oral diflunisal for acute postoperative pain in adults"
Anti-inflammatory products (M01A) Pyrazolidine/Butylpyrazolidines Ampyrone • Clofezone • Kebuzone • Metamizole • Mofebutazone • Oxyphenbutazone • Phenazone • Phenylbutazone • Sulfinpyrazone • Feprazone •Acetic acid derivatives
and related substancesAceclofenac • Acemetacin • Alclofenac • Bromfenac • Bumadizone • Bufexamac • Diclofenac • Difenpiramide • Etodolac • Fentiazac • Indometacin • Ketorolac • Lonazolac • Oxametacin • Proglumetacin • Sulindac • Tolmetin • Zomepirac • AmfenacOxicams Propionic acid derivatives Alminoprofen • Benoxaprofen • Dexibuprofen • Dexketoprofen • Fenbufen • Fenoprofen • Flunoxaprofen • Flurbiprofen • Ibuprofen • Ibuproxam • Indoprofen • Ketoprofen • Naproxen • Oxaprozin • Pirprofen • Suprofen • Tiaprofenic acidFenamates Coxibs Other Analgesics (N02A, N02B) Opioids
See also: Opioids templateOpium & alkaloids thereofSemi-synthetic opium
derivativesSynthetic opioidsAlphaprodine • Anileridine • Butorphanol • Dextromoramide • Dextropropoxyphene • Dezocine • Fentanyl • Ketobemidone • Levorphanol • Methadone • Meptazinol • Nalbuphine • Pentazocine • Propoxyphene • Propiram • Pethidine • Phenazocine • Piminodine • Piritramide • Tapentadol • Tilidine • Tramadol
Pyrazolones Cannabinoids Anilides Non-steroidal
anti-inflammatories
See also: NSAIDs templatePropionic acid classFenoprofen • Flurbiprofen • Ibuprofen# • Ketoprofen • Naproxen • Oxaprozin
Oxicam classAcetic acid classDiclofenac • Indometacin • Ketorolac • Nabumetone • Sulindac • Tolmetin
Celecoxib • Rofecoxib • Valdecoxib • Parecoxib • Lumiracoxib
Anthranilic acid
(fenamate) classMeclofenamate • Mefenamic acid
SalicylatesAspirin (Acetylsalicylic acid)# • Benorylate • Diflunisal • Ethenzamide • Magnesium salicylate • Salicin • Salicylamide • Salsalate • Trisalate • Wintergreen (Methyl salicylate)
Atypical, adjuvant and potentiators,
Metabolic agents and miscellaneousAmitryptiline • Befiradol • Bicifadine • Carisoprodol • Camphor • Cimetidine • Clonidine • Chlorzoxazone • Cyclobenzaprine • Duloxetine • Esreboxetine • Flupirtine • Gabapentin • Glafenine • Hydroxyzine • Ketamine • Menthol • Mephenoxalone • Methocarbamol • Nefopam • Orphenadrine • Pregabalin • Proglumide • Scopolamine • Tebanicline • Trazodone • Gabapentin enacarbil • ZiconotideSalicylic acid • Aspirin • Aloxiprin • Methyl salicylate • Magnesium salicylate • Ethyl salicylate • Bismuth subsalicylate • Sodium salicylate • Salicylamide • Salicin • Benorilate • Salsalate • Ethenzamide • Diflunisal • Trolamine salicylate • Homosalate • Salicylmethylecgonine • Octyl salicylate • Aluminon • Benzyl salicylate • Copper aspirinate • Potassium salicylateCategories:- Non-steroidal anti-inflammatory drugs
- Salicylic acids
- Organofluorides
- Biphenyls
- InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)
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