diclofenaco (also known as diclofenac ) is relatively not-selective Medicine inhibiting of Ciclooxigenasa and member of the family of nonesteroideos antiinflammatories ( AINEs indicated to reduce inflammations and like analgesic, reducing to pains caused by wounds smaller and as intense pains as those Arthritis . Also it is possible to be used to reduce cólicos menstrual .

Chemistry of the drug

The diclofenaco is a fenilacético derivative, whose chemical name is acetic the 2-fenil acid], with the chemical formula C14-H11-Cl2-NO2=0).

Mechanism of action

The time of action of a dose (of 6 to 8 hours) is generally much greater than the short lapse indicated in commercial products. This can partly be due to a concentration elevated of Drug in the sinoviales fluids.

The exact mechanism of action is not totally shortage, but it thinks that the mechanism primary, responsible for its anti-inflammatory and analgesic action is the avoidance of the synthesis of Prostaglandins caused by the inhibition of the enzyme Ciclooxigenasa (COX).

The inhibition of the COX also diminishes the production of Prostaglandins in Epitelio of Stomach, making it much more to the corrosion by acid gastric vulnerable. This it is the main indirect effect of the diclofenaco. The diclofenaco owns moderate a low preference to (approximately ten times) blocking isoenzima COX2 and it thinks that for that reason it owns a low incidence of gastrointestinal negative effects that shown by Indometacina and Aspirina .

Evidences exist of which the diclofenaco inhibits the functions of Lipooxigenasa, reason why reduces to the formation of Leucotrienos (inflammatory substances). Also it is speculated on that the diclofenaco inhibits the production of Enzyme Fosfolipasa A2 in its mechanism of action. These additional actions explain their high effectiveness.

There are noticeable differences between the antiinflammatories nonesteroideos in his selective inhibition of both subtypes of Ciclooxigenasa, COX-1 and COX-2. Many medecines have been designed to concentrate in the COX-2 inhibition as a form to diminish the gastrointestinal effects of others AINES (antiinflammatories nonesteroideos) like Aspirina . Actually, the use of some inhibiters of COX-2 has brought consequently numerous cardiac unemployments of patients who did not resist the treatment, nevertheless, another significant group of COX patients using inhibiting, like the diclofenaco, perfectly has been tolerated.

Indications

The diclofenaco is used for musculo-skeletal sufferings, especially arthritis ( reumatoide Arthritis, Osteoartritis, espondiloartritis, ankylosing Spondylitis ), attacks of drop and handling of the pain caused by renal and vesicular calculations. An additional indication is the treatment of Migrañas acute. The diclofenaco is used regularly subsequent to treat moderate the slight pain to Surgery or after a traumatic process, particularly when there is present inflammation. Drug is effective against menstrual Pain . In Supositorios rectal, the diclofenaco can be considered the medicine of first election for preventive Analgesia and Nausea posoperatoria.

The use of long term diclofenaco, as with others AINES (antiinflammatories nonesteroideos) predisposes to the appearance of peptic ulcers, reason why many patients with this predisposition receive treatment of diclofenaco in combination with Misoprostol, a synthetic analog of Prostaglandins that protects the gastric mucosa in a single product (Arthrotec®, Artrotec® in countries of Hispanic speech).

A product with diclofenaco to 3% with gel base has made available for the treatment of actinic Queratosis, which is a suffering caused by an overexposure to the solar light (Solareze®). Also, some countries have approved the use of the gel with diclofenaco to treat musculo-skeletal conditions.

Presentations with license also exist free sale without prescription to be used against slight pains and fever associated with common infections.

Many countries sell to the public eye-drops to treat the acute and chronic inflammation, not caused by bacteria, in the forcebody of the eye (for example in states post surgery). The mark name is ophthalmic Voltarén.

Investigated uses not prospected

The diclofenaco is used often to deal the associate chronic pain with Cancer, particularly if Inflammation is presence of . is step I of the therapeutic scheme of the WHO (World-wide Organization of the Health) to fight the chronic pain. In women with Cancer of sine and in the pain associated with bony Metastasis has been appraised good results (sometimes better than in Opiate ).

In necessary case, the diclofenaco can be combined with Opiate derivatives . In Europe trade names with a combination of diclofenaco and exist Codeine at the rate of 50  mg of each component (Combarén®) for the treatment of the pain Cancer . Also combinations of diclofenaco with psychoactive drugs exist such as Cloroprotixeno and Amitriptilina, that - according to certain investigations they can be useful in certain number of patients with cancer.

Fever caused by Linfogranulomatosis vitiates ( Linfoma de Hodgkin ) can respond to the diclofenaco. The treatment can finalize at the same time in which the usual treatment with radiation or Chemotherapy causes remission of the fever.

The diclofenaco can avoid the development of Disease of Alzheimer if it is administered daily to low doses by several years. All the investigations were stopped after finding that some AINES (antiinflammatories nonesteroideos) investigated - as Naproxeno and Rofecoxib - they had a high incidence of deaths by cardiovascular events and cerebrovascular accidents compared against Placebo .

One has seen that the diclofenaco elevates sanguineous Pressure in patients with Shy-Drager Syndrome ( independent Hypotension ) that sometimes appears in patients with Diabetes . At the moment, this is in investigation reason why it is not recommended like routine treatment.

It has been observed that the diclofenaco is effective against all the stocks of E. coli (Escherichia coli) resistant to multiple drugs with one CIM ( minimum Concentration inhibiting ) of 25 microg/mL. Therefore, the diclofenaco has been suggested has the capacity to treat the ITU (infections of the urinary tract) noncomplicated caused by E.

Contraindications

  • Hypersensitivity recognized the diclofenaco.

  • History of allergic reactions (broncoespasmo, shock, rinitis, urticaria) followed the use of Aspirina (r) or others AINEs
  • Third trimester of pregnancy.
  • stomach and/or duodenal Ulceration activates.
  • Gastrointestinal bleeding.
  • Intestinal inflammatory sufferings such as Disease of Crohn or ulcerativa colitis.
  • Severe cardiac insufficiency (according to the classification of the Cardiological Association of New York NYHA III/IV).
  • Recently Administration of Drugs and Foods (FDA by its abbreviations in English) has warned not to deal with this one Drug to convalescent patients cardiac surgery.
  • Severe hepatic insufficiency (Class C, according to Child-Pugh Scale ).
  • Severe renal insufficiency (purification of Creatinine <30 ml/min).
  • It is necessary to have well-taken care of in patients with preexisting Porfiria hepatic since the diclofenaco can shoot the attacks.
  • Special care is due to have in patients with severe bleeding (like cerebral hemorrhage).
  • Impotence.

Indirect effect

  • the diclofenaco is between AINES (antiinflammatories nonesteroideos) better tolerated. Nevertheless, 20% of the patients in long term treatments undergo indirect effect and, of these, a 2% must discontinue the use of mainly Drug had to gastrointestinal effects, hidden gastrointestinal sangramiento and ulceration gastric-although the ulcers happen with smaller frequency than the one of another AINEs.

  • The problems that are seen more actually are the gastrointestinal ones. The development of ulcerations or bleeding requires immediate completion of the therapy under diclofenaco. Like Prophylaxes during the long treatments, the majority of the patients can receive some Drug ulcerate-protector (like 150  mg of Ranitidina or Misoprostol when lying down, 20  mg of Omeprazol when lying down).
  • Little bony Marrow frequents is the depression of ( Leukopenia, Agranulocitosis, Trombopenia with or without Purple, aplásica Anemia ). In case of being detected delayed, these conditions can be a threat against the life and being of irreversible character. All the patients must be monitored close by. The diclofenaco is a weak and reversible inhibiter of the trombocítica aggregation, event required for a normal sanguineous coagulation.
  • Renal and hepatic damage happens infrequently, although they are usually reversible. Hepatitis can happen rarely without no symptom of warning and could be fatal. The patients with Osteoartritis more frequently develop symptoms of hepatic disease that the patients with reumatoide Arthritis . The renal and hepatic function will have to be monitored regularly during the treatments long play. If the diclofenaco is used in short treatments of pain or Fever, the diclofenaco has not been found responsible to cuasar greater hepatotoxic damage than any other AINE. Elevations of enzymes are observed aminotransferases with more frequency with the use of diclofenac that with another AINEs.
  • The diclofenaco specifically is known to cause renal fault in Asian vultures ( Sees Environmental Problems). Some human species and individuals that are sensible to a drug are initially suspicious of not expressing some missing genes related to specific enzymes of detoxication of the drug. Since the individuals majors have one reduced expression of all the enzyme levels, the metabolism of the old ones could come near gradually to observed and the vultures, becoming in this way unexpectedly vulnerable and intolerant the diclofenaco.
  • The AINEs " they are associate with adverse renal effects caused by the reduction of the renal synthesis of prostaglandinas" in sensible people or animal species, and potencialmnte during the use by long periods in nonsensible people, the resistance to the effects collaterals falls with the age. Unfortunately this effect collateral cannot simlemente be avoided by the use of a selective inhibiter COX-2 because, " Both isoformas of COX, COX-1 and COX-2, are expressed in the kidney. Consequently, the same precautions related to the risk of renal damage that are observed for AINEs nonselective, will have also to be observed when inhibiting selctivos COX-2 are administrados." *Posteriro to the identification of the increased risk of cardiac attacks with Inhibiting COX-2 Rofecoxib in the 2004, the attention has focused in all the other members of the group AINEs, including the diclofenaco. The investigation results are a mixture of article put-analysis and reports acualizados until April of the 2006 that relatively suggests an increased rank of cardiac disease of 1, g3 compared to the nonusuary ones. Professor Peter Weissberg, Medical Director of the British Foundation of the Heart said, " Nevertheless, the increased risk is small and many patients with debilitating chronic pain could feel very well that this small risk is worth the pain in order to alleviate his síntomas". Only Naproxeno has been found like the unique one in not increasing the risk of cardiac disease, nevertheless it is known that naproxeno has a greater rank to produce gastric ulcer that diclofenaco.
    an ample subsequent study of 74.838 users of AINEs or coxibs, published in May 2006 did not find additional cardiovascular risk by the use of the diclofenaco.

Pharmaceutical forms

Voltarén and Voltarol contain diclofenaco sodium salts. In the United Kingdom Voltarol only can be replaced with other salts of sodium or potassium

The diclofenaco is available in resistant formulations to the gastric acids (25 and 50  mg ), compressed expresses efevescentes (50  mg), forms of liberation slow and controlled (75, 100 or 150  mg), supositorios (50 and 100  mg), and in injectable formulas (50 and 75  mg).

In some countries the diclofenaco is a medicine of free sale (OTC: to over to counter or `upon the counter'):

  • Voltarén Dolo (12,5  diclofenaco mg like a potassium salt) in Switzerland and Germany, and
  • preparations with 25  mg of diclofenaco in New Zealand .

The combination of diclofenaco with Misoprostol is a preparation that the gastrointestinal ulceration diminishes, but cause Diarrhea in some users. Another combination of the diclofenaco, this time with Omeprazol had effectiveness in reducing to the sangramiento risk appellant, but renal adverse effects in certain patients of high risk noticed. The diclofenaco to 150 doses of mg/día seems to reduce to the renal sanguineous flow and the rate of filtration to glomerular. An ophthalmic preparation to 0.1% is recommended for the prevention of the ophthalmic inflammations posoperatorias and can be used after implants of lens and the operations of Estrabismo .

Presentation

In the majority of the countries, this medicine is provided in potassium salts, nevertheless, in the United Kingdom, in Mexico, EE. and Spain also can be found like sodium salts. The diclofenaco also is available of generic way in many formulations of other medecines. Their indirect effect are profiteers to alleviate to pains smaller and fevers associated with common infections. In some countries of Europe diclofenac is available in preparations for intramuscular administration and like a mouthwash.

One has demonstrated that the veterinary use of the diclofenaco in some countries like India, has caused to an important loss in the population of Vultures causing an important ecological disaster. The previous thing is because these animal develop diseases in the kidney by dead the animal ingestion dealt with the drug.

Ecological problems

It has been reported that the veterinary use of diclofenaco has taken to an acute decrease in the population of Vultures in the Indian subcontinent, until of a 95% in certain areas. The mechanism of the death is probably renal Falla, that is a well-known indirect effect of the diclofenaco. The vultures veterinary eat the rest of domestic animal dealt with diclofenaco, and they are poisoned due to the accumulated chemical element. During the meeting of the National Wildlife Board in March of 2005, the government of India announced that he hopes to finish with the use of diclofenaco in animales. The candidate to replace to the diclofenaco is the Meloxicam, that is safer (although more expensive). Government of India challenges one of those consequences ace to vulture species extinction. Westerners may not initially appreciate how to major shift in feral transfer of corpse pathogens from vultures to dogs and rats dog lead to disease pandemic causing millions of deaths in a crowded country like India.

The loss of vultures there are had to social impact on the Indian Zoroastrian Parsi community, who traditionally uses vultures to dispose of human corpses in " sky burials", and plows now having to seek alternative disposal methods.

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References and notes

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