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Diclofenac

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Generality
Pharmacological properties
Pharmacokinetics
Therapeutic uses
Side effects
Overdose

Generality

diclofenac chemical formula

Diclofenac is the most commonly used "non-steroidal anti-inflammatory drug" (NSAID) in Europe, with different trade names, the best known of which are Voltaren, Voltadol, Dicloreum, Deflamat, Akis, Dealgic, Fenadol, Zeroflog.

Currently the Diclofenac is also available as a generic drug and it is therefore possible to find several formulations of diclofenac prepared by various pharmaceutical companies: Diclofenac EG, Diclofenac DOC, Diclofenac HEXAL, Diclofenac MYLAN GENERICS ecc.

As with all NSAIDs, diclofenac has an analgesic, antipyretic and anti-inflammatory action, and is then used in all forms of pain (backpain, sciatica, hip pain, kneem pain, periarthritis, osteoarthritis, dental pain etc.), in infectious and non-infectious febrile forms and generally in inflammatory states.

The Italian Agency for Medicines (AIFA) has not recommended to use NSAIDs and therefore diclofenac, for prolonged periods: recent epidemiological studies have in fact demonstrated an increased incidence of heart rhythm disorders (increase QTc interval) potentially dangerouse.

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Pharmacological properties

Diclofenac has analgesic, antipyretic and anti-inflammatory actions and acts by inhibiting the cyclooxygenase-2 (COX2). His power toward the COX-2 is substantially higher than that of indomethacin, naproxen and numerous other non-steroidal anti-inflammatory drugs (NSAIDs). Furthermore, diclofenac seems able to reduce the intracellular concentrations of free arachidonic acid in leukocytes, probably altering the release or uptake.

The selectivity of diclofenac to the COX-2 is similar to that of celecoxib (Celebrex). In fact, the incidence of serious gastrointestinal side effects (mainly digestive bleeding) did not differ between celecoxib and diclofenac in the CLASS study (Juni et al., 2002). In addition, prospective studies have suggested a cardiovascular risk associated with chronic treatment with diclofenac. It is currently taking a comparative randomized study on a large scale between the diclofenac and the selective COX-2 inhibitor celecoxib.

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Pharmacokinetics

Diclofenac has a rapid absorption, a high protein binding and a short half-life. Since undergoes significant first pass effect, only 50% is available in the systemic circulation.

Diclofenac accumulates in synovial fluid following oral administration, which may explain why the duration of its therapeutic effect proves considerably greater than its plasma half-life.

It is metabolized in the liver by a member of the subfamily of CYP2C 4-hydroxy-diclofenac, the major metabolite, and other hydroxylated forms; After glucuronidation and sulfation metabolites are excreted in the urine (65%) and bile (35%).

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Therapeutic uses

Diclofenac has been approved for the symptomatic treatment of rheumatoid arthritis in the long term, osteoarthritis and ankylosing spondylitis. Diclofenac is also useful in the short-term treatment of acute musculoskeletal pain, postoperative pain and dysmenorrhea.

The diclofenac is also available in combination with misoprostol, a synthetic analogue of prostaglandin E1 which exerts cytoprotective action on the gastrointestinal mucosa, and this combination, which maintains the efficacy of diclofenac simultaneously reducing the frequency of gastrointestinal ulcers and erosions, has a good cost-benefit ratio than the selective COX-2, despite the extra cost of misoprostol. Furthermore, it is provided an ophthalmic solution of diclofenac for the treatment of post-operative pain after cataract surgery.

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Side effects

Diclofenac causes side effects (in particular gastrointestinal) in approximately 20% of patients and approximately 2% of these must discontinue therapy. In 5-15% of patients will experience a modest increase in liver transaminases.

Although normally the intervention of transaminases is moderate, in a small percentage of patients may increase the value of three times. The upside is usually reversible but transaminases should always be dosed during the first 8 weeks of treatment with diclofenac and treatment should be stopped if excessive values ??persist or occur other signs or symptoms.

The side effects of diclofenac include disorders of the CNS, rashes, allergic reactions, fluid retention and edema, and, rarely, renal impairment. The drug is not recommended for children, during lactation or pregnancy. Due to its relative specificity for COX-2, on the contrary ibuprofen, diclofenac does not interfere with the antiplatelet effect of aspirin. In view of these observations, diclofenac does not represent a viable alternative to a COX-2 selective inhibitor in individuals at risk for cardiovascular or cerebrovascular disease.

The following table summarizes the side effects of diclofenac:

Blood and lymphatic system disorders
Very rare:thrombocytopenia, leukopenia, anemia (including haemolytic and aplastic anemia), agranulocytosis
Immune system disorders
Rare:hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock)
Very rare:angioneurotic edema (including facial edema)
Psychiatric disorders
Very rare:disorientation, depression, insomnia, nightmares, irritability, psychotic reactions
Nervous system disorders
Common:headache, dizziness
Rare:drowsiness
Very rare:paresthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident
Eye disorders
Very rare:disturbances of vision, blurred vision, diplopia
Ear and labyrinth disorders
Common:dizziness
Very rare:tinnitus, hearing deterioration
Heart diseases
Uncommon*:myocardial infarction, heart failure, palpitations, chest pain
Vascular disorders
Very rare:hypertension, vasculitis
Respiratory, thoracic and mediastinal disorders
Rare:Asthma (including dyspnoea)
Very rare:pneumonia
Gastrointestinal disorders
Common:nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, loss of appetite
Rare:gastritis, gastrointestinal bleeding, vomiting blood, bloody diarrhea, melaena, gastrointestinal ulcer (with or without bleeding and perforation)
Very rare:Colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis
Hepatobiliary disorders
Common:increased transaminases
Rare:hepatitis, jaundice, liver disorders
Very rare:fulminant hepatitis, liver necrosis, liver failure
Skin and subcutaneous tissue disorders
Common:rash
Rare:urticaria
Very rare:bullous dermatitis, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, hair loss, photosensitivity reactions, purpura, Henoch Schonlein purpura, pruritus
Renal and urinary disorders
Very rare:acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis
General disorders and administration site conditions
Rare:oedema

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Overdose

There is no typical clinical picture resulting from an overdose of diclofenac. Overdose can cause symptoms such as vomiting, gastrointestinal haemorrhage, diarrhea, dizziness, tinnitus or convulsions. In the event of significant poisoning it is possible acute renal failure and liver damage.

In case of overdose, treatment essentially consists of supportive and symptomatic measures. In case of complications such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression should be taken to support and symptomatic treatment measures.

Specific therapies such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating NSAIDs, including diclofenac, due to their high binding to plasma proteins and their significant metabolism.

After ingestion of a potentially toxic overdose can be considered the use of activated carbon, while after ingestion of a potentially dangerous overdose for life can be considered gastric emptying (p. Eg. Vomiting, gastric lavage).

 

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Pagina aggiornata il: 30/05/2016