Citizendia
Your Ad Here

Diclofenac
Systematic (IUPAC) name
2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid
Identifiers
CAS number 15307-86-5
ATC code M01AB05 M02AA15, S01BC03
PubChem 3033
DrugBank APRD00527
Chemical data
Formula C14H11Cl2NO2 
Mol. mass 296. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. A section of the Anatomical Therapeutic Chemical Classification System. A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Chlorine (ˈklɔriːn from the Greek word 'χλωρóς' ( khlôros, meaning 'pale green' is the Chemical element with Atomic number 17 and Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 148 g/mol
Pharmacokinetic data
Bioavailability 100%
Protein binding more than 99%
Metabolism hepatic, no active metabolites exist
Half life 1. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 2-2 hr (35% of the drug enters enterohepatic recirculation)
Excretion biliary, only 1% in urine
Therapeutic considerations
Pregnancy cat.

A(AU) B (1st. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. and 2nd. trimenon), X (third trimenon)
Legal status

POM(UK) Rx-only most preparations/countries. The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located Limited OTC some countries
Routes oral, rectal, im, iv (renal- and gallstones), topical

Diclofenac (marketed as MOBIDIC, Flector patch, Voltaren, Voltarol, Diclon, Dicloflex Difen, Difene, Cataflam, Pennsaid, Rhumalgan, Modifenac, Abitren, Voveran, Arthrotec and Zolterol, with various drug dose combinations) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and as an analgesic reducing pain in conditions such as arthritis or acute injury. In Pharmacology and Toxicology, a route Intramuscular injection is the injection of a substance directly into a Muscle. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Arthrotec the brand name for a product that contains Diclofenac sodium Nonsteroidal anti-inflammatory drug (NSAID with Analgesic properties Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Arthritis (from Greek arthro-, joint + -itis, inflammation plural arthritides is a group of conditions involving damage to the Joints of the body Injury or bodily injury is Damage or Harm caused to the Structure or function of the Body caused by an outside agent or It can also be used to reduce menstrual pain, dysmenorrhea. The menstrual cycle is a recurring cycle of physiologic changes that occurs in reproductive-age Females Overt menstruation (where there is blood flow from the Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Dysmenorrhea (or dysmenorrhoea) is a medical condition characterized by severe Uterine Pain during Menstruation. The name is derived from its chemical name: 2-(2,6-dichloranilino) phenylacetic acid

In the United Kingdom, India, and the United States, it may be supplied as either the sodium or potassium salt, in China most often as the sodium salt, while in some other countries only as the potassium salt. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located India, officially the Republic of India (भारत गणराज्य inc-Latn Bhārat Gaṇarājya; see also other Indian languages) is a country The United States of America —commonly referred to as the Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 A salt, in Chemistry, is defined as the product formed from the neutralisation reaction of Acids and bases. Diclofenac is available as a generic drug in a number of formulations. Over the counter (OTC) use is approved in some countries for minor aches and pains and fever associated with common infections. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter"


Contents

Mechanism of action

The action of one single dose is much longer (6 to 8 hours) than the very short half-life that the drug indicates. This could partly be due to a particular high concentration achieved in synovial fluids. Synovial fluid is a thick stringy fluid found in the cavities of Synovial joints With its egg-like consistency ("synovial" partially derives from ovum,

The exact mechanism of action is not entirely known, but it is thought that the primary mechanism responsible for its anti-inflammatory / antipyretic / analgesic action is inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX). Anti-inflammatory refers to the property of a substance or treatment that reduces Inflammation. Antipyretics are Drugs that reduce body temperature in situations such as Fever. A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body

Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following Gastric acid is one of the main Secretions of the Stomach, together with several Enzymes and Intrinsic factor. This is also the main side effect of diclofenac. Diclofenac has a low to moderate preference to block the COX2-isoenzyme (approximately 10-fold) and is said to have therefore a somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin. Indometacin ( INN Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve

Diclofenac may also be a unique member of the NSAIDs. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher There is some evidence that diclofenac inhibits the lipoxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). Lipoxygenases ( are a family of Iron -containing Enzymes that catalyse the Dioxygenation of Polyunsaturated Fatty acids in Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response There is also speculation that diclofenac may inhibit phospholipase A2 as part of its mechanism of action. A phospholipase is an enzyme that converts Phospholipids into Fatty acids and other Lipophilic substances These additional actions may explain the high potency of diclofenac - it is the most potent NSAID on a broad basis.

There are marked differences among NSAIDs in their selective inhibition of the two subtypes of cyclo-oxygenase, COX-1 and COX-2. Much pharmaceutical drug design has attempted to focus on selective COX-2 inhibition as a way to minimize the gastrointestinal side effects of NSAIDs like aspirin. In practice, use of some COX-2 inhibitors due to their adverse effects has led to massive numbers of patient family lawsuits alleging wrongful death by heart attack, yet other significantly COX-selective NSAIDs like diclofenac have been well-tolerated by most of the population. COX-2 selective inhibitor is a form of Non-steroidal anti-inflammatory drug (NSAID that directly targets COX-2, an Enzyme responsible for Inflammation An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply

Indications

Combined Diclofenac sodium and misoprostol tablets.
Combined Diclofenac sodium and misoprostol tablets.

Diclofenac is used for musculoskeletal complaints, especially arthritis (rheumatoid arthritis, osteoarthritis, spondylarthritis, ankylosing spondylitis), gout attacks, and pain management in case of kidney stones and gallstones. Arthritis (from Greek arthro-, joint + -itis, inflammation plural arthritides is a group of conditions involving damage to the Joints of the body Ankylosing spondylitis ( AS; previously known as Bechterew's disease, Bechterew syndrome, Marie Strümpell disease and a form of Spondyloarthritis Gout (also called metabolic arthritis) is a disease created by a buildup of Uric acid. Pain management (also called pain medicine is the medical discipline concerned with the relief of Pain. Kidney stones, also called renal calculi, are solid concretions (crystal aggregations of dissolved minerals in Urine; calculi typically form In Medicine, gallstones (choleliths are Crystalline bodies formed within the body by accretion or concretion of normal or abnormal Bile component An additional indication is the treatment of acute migraines. Diclofenac is used commonly to treat mild to moderate post-operative or post-traumatic pain, particularly when inflammation is also present, and is effective against menstrual pain.

Diclofenac suppositories
Diclofenac suppositories

As long-term use of diclofenac and similar NSAIDs predisposes for peptic ulcer, many patients at risk for this complication are prescribed a combination (Arthrotec) of diclofenac and misoprostol, a synthetic prostaglandin analogue, to protect the gastric mucosa. A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 Arthrotec the brand name for a product that contains Diclofenac sodium Nonsteroidal anti-inflammatory drug (NSAID with Analgesic properties Misoprostol is a drug that is FDA -approved in the United States for the prevention of non-steroidal anti-inflammatory drug ( NSAID)-induced

An external, gel-based form of diclofenac (Solareze) is available for the treatment of facial actinic keratosis which is caused by over-exposure to sunlight. Actinic keratosis (also called solar keratosis, or AK) is a Premalignant condition of thick scaly or crusty patches of skin Some countries have also approved the external use of diclofenac gel to treat muskoskeletal conditions.

Over-the-counter use against minor aches and pains and fever associated with common infections is also licensed in some countries, such as Australia and New Zealand.

In many countries eye-drops are sold to treat acute and chronic non-bacterial inflammations of the anterior part of the eyes (e. g. postoperative states). A common brand name is Voltaren-ophta.

Off label/investigational uses

Diclofenac is often used to treat chronic pain associated with cancer, particularly if inflammation is also present (Step I of the World Health Organisation (WHO) Scheme for treatment of chronic pain). Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Good results (sometimes better than those with opioids) have been seen in female breast cancer and in the pain associated with bony metastases. Diclofenac can be combined with opioids if needed. In Europe Combaren exists, a fixed combination of diclofenac and codeine (50 mg each) for cancer treatment. Combinations with psychoactive drugs such as chlorprothixene and/or amitriptyline have also been investigated and found useful in a number of cancer patients. Chlorprothixene is a Typical antipsychotic drug of the Thioxanthene class Amitriptyline (or Amitryptyline) hydrochloride (sold as Elavil Tryptanol Endep Elatrol Tryptizol Trepiline Laroxyl Saroten is a Tricyclic antidepressant

Fever due to malignant lymphogranulomatosis (Hodgkin's lymphoma) often responds to diclofenac. Hodgkin's lymphoma, also known as Hodgkin's disease is a type of Lymphoma first described by Thomas Hodgkin in 1832 Treatment can be terminated as soon as the usual treatment with radiation and/or chemotherapy causes remission of fever.

Diclofenac may prevent the development of Alzheimer's disease if given daily in small doses during many years. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. All investigations were stopped after it was found that some of the other investigated NSAIDs (naproxen, rofecoxib) caused a higher incidence of death cases due to cardiovascular events and stroke compared to placebo.

Diclofenac has been found to increase the blood pressure in patients with Shy-Drager syndrome (autonomous hypotension) often seen in diabetic patients. Shy-Drager syndrome is a rare progressively Degenerative disease of the Autonomic nervous system. In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Currently, this use is highly investigational and cannot be recommended as routine treatment.

Diclofenac has been found to be effective against all strains of multi drug resistant E. coli, with a MIC of 25 microg/mL. Therefore, it may be suggested that diclofenac has the capacity to treat UTI (uncomplicated urinary tract infections) caused by E. coli. [1] It has also been shown to be effective in treating Salmonella infections in mice [2] and is under investigation for the treatment of tuberculosis[3].

Its mechanism of action is not clear yet but it appears to inhibit DNA systhesis. [4]

Contraindications

Side effects

Cardiac

Gastrointestinal

Hepatic

Renal

Other

Formulations

Enteric Coated Diclofenac Sodium tablets by Dexel-Pharma Ltd.
Enteric Coated Diclofenac Sodium tablets by Dexel-Pharma Ltd. An enteric coating is a barrier applied to oral Medication that controls the location in the Digestive system where it is absorbed

Flector Patch is a minimally systemic topical patch formulation of diclofenac. It is indicated for acute pain due to minor sprains, strains, and contusions. The patch has been approved in many other countries outside the U. S. A under different brand names.

Voltaren and Voltarol contain the sodium salt of diclofenac. In the United Kingdom Voltarol can be supplied with either the sodium salt or potassium salt, while Cataflam in some other countries is the potassium salt only. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located

Diclofenac is available in stomach acid resistant formulations (25 and 50 mg), fast disintegrating oral formulations (50 mg), slow- and controlled-release forms (75, 100 or 150 mg), suppositories (50 and 100 mg), and injectable forms (50 and 75 mg). For other uses of the words gram or gramme see Gram (disambiguation.

Diclofenac is also available over the counter (OTC) in some countries: Voltaren dolo (12. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" 5 mg diclofenac as potassium salt) in Switzerland and Germany, and preparations containing 25 mg diclofenac in New Zealand. Switzerland (English pronunciation; Schweiz Swiss German: Schwyz or Schwiiz Suisse Svizzera Svizra officially the Swiss Confederation Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. New Zealand is an Island country in the south-western Pacific Ocean comprising two main landmasses (the North Island and the South Island

Ecological problems

Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent, up to 95% in some areas. Old World vultures belong to the family Accipitridae, which also includes Eagles Buzzards kites and Hawks Old World vultures [10] The mechanism is probably renal failure, a known side-effect of diclofenac. Renal failure or kidney Vultures eat the carcasses of domesticated animals that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical. At a meeting of the National Wildlife Board in March 2005, the Government of India announced that it intended to phase out the veterinary use of diclofenac. [11] Meloxicam is a safer (though more expensive) candidate to replace use of diclofenac. Meloxicam is a Nonsteroidal anti-inflammatory drug used to relieve the symptoms of Arthritis, primary Dysmenorrhea, Fever; and as an Analgesic [12] "The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian subcontinent that pose a potential threat to human health. In many places, populations of feral dogs (Canis familiaris [sic]) have benefited from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses. The dog ( Canis lupus familiaris) is a domesticated Subspecies of the gray wolf, a Mammal of the Canidae family of the order The Gyps vultures are a genus of Old World vultures in the Bird family Accipitridae which also includes Eagles kites Buzzards Ungulates (meaning roughly "being Hoofed quot or "hoofed animal" are several groups of Mammals most of which use the tips of their toes usually Associated with the rise in dog numbers is an increased risk of human cases of rabies. "[12]

The Government of India cites one of those major consequences as a vulture species extinction. [11] A major shift in transfer of corpse pathogens from vultures to feral dogs and rats can lead to a disease pandemic causing millions of deaths in a crowded country like India.

The loss of vultures has had a social impact on the Indian Zoroastrian Parsi community, who traditionally use vultures to dispose of human corpses in "sky burials" (Towers of Silence), and are now having to seek alternative disposal methods. Zoroastrianism (ˌzɔroʊˈæstriəˌnɪzəm is the religion and philosophy based on the teachings Sky burial or ritual Dissection was once a common funerary practice in Tibet wherein a human corpse is cut into small pieces and placed on a mountaintop Towers of Silence are circular raised structures used by Zoroastrians for exposure of the dead [12]

In Punjab it appears that vulture numbers are slowly rising after use of the drug was discontinued. Punjab (ਪੰਜਾਬ पंजाब pəɲdʒaːb is a state in northwest India.

Diclofenac was shown also to cause harm to freshwater fish species as rainbow trout [Schwaiger et al. (2004). Aquat. Toxicol. 68(2): 141-150;Triebskorn et al. (2004). Aquat. Toxicol. 68(2): 151-166; Schwaiger & Triebskorn (2005). UBA-Berichte 29/05: 217-226. Triebskorn et al. (2007). Analyt. Bioanalyt. Chem. 387(4): 1405-1416. )

See also

References

  1. ^ Mazumdar K, Dutta NK, Dastidar SG, Motohashi N, Shirataki Y (2006). The Indian White-rumped Vulture ( Gyps bengalensis) is an Old World vulture in the family Accipitridae, which also includes Eagles The Slender-billed Vulture ( Gyps tenuirostris) is a recently recognized Species of Old World vulture. Towers of Silence are circular raised structures used by Zoroastrians for exposure of the dead "Diclofenac in the management of E. coli urinary tract infections". In Vivo 20 (5): 613–619. PMID 17091768.  
  2. ^ Dutta NK, Annadurai S, Mazumdar K, Dastidar SG, Kristiansen JE, Molnar J, Martins M, Amaral L. (2007). "Potential management of resistant microbial infections with a novel non-antibiotic: the anti-inflammatory drug diclofenac sodium. ". Int. J. Antimicrob. Agents 30 (3): 242-249.  
  3. ^ Dutta NK, Mazumdar K, Dastidar SG, Park JH (2007). "Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice. ". Int. J. Antimicrob. Agents 30 (4): 336-340.  
  4. ^ Dutta NK, Annadurai S, Mazumdar K, Dastidar SG, Kristiansen JE, Molnar J, Martins M, Amaral L (2000). "The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis. ". Int. J. Antimicrob. Agents 14 (3): 249-51.  
  5. ^ Kearney P, Baigent C, Godwin J, Halls H, Emberson J, Patrono C (2006). "Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. ". BMJ 332 (7553): 1302-8. doi:10.1136/bmj.332.7553.1302. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16740558.  
  6. ^ Solomon D, Avorn J, Stürmer T, Glynn R, Mogun H, Schneeweiss S (2006). "Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. ". Arthritis Rheum 54 (5): 1378-89. doi:10.1002/art.21887. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16645966.  
  7. ^ FitzGerald G, Patrono C (2001). "The coxibs, selective inhibitors of cyclooxygenase-2". N Engl J Med 345 (6): 433-42. doi:10.1056/NEJM200108093450607. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11496855.  
  8. ^ Graham D (2006). "COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense". JAMA 296 (13): 1653-6. doi:10.1001/jama.296.13.jed60058. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16968830.  
  9. ^ a b Brater DC (2002). "Renal effects of cyclooxygyenase-2-selective inhibitors". J Pain Symptom Manage 23 (4 Suppl): S15-20; discussion S21-3. doi:10.1016/S0885-3924(02)00370-6. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11992745.  
  10. ^ Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJ, Arshad M, Mahmood S, Ali A, Khan AA (2004). "Diclofenac residues as the cause of vulture population decline in Pakistan". Nature 427 (6975): 630-3. doi:10.1038/nature02317. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14745453.  
  11. ^ a b Press Information Bureau, Government of India (2005-05-16). Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. Events 1204 - Baldwin IX Count of Flanders is crowned as the first Emperor of the Latin Empire. "Saving the Vultures from Extiction". Press release. A news release, media release, press release or press statement is a written or recorded Communication directed at members of the News Retrieved on 2006-05-12. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1191 - Richard I of England marries Berengaria of Navarre.
  12. ^ a b c Swan G, Naidoo V, Cuthbert R, Green RE, Pain DJ, Swarup D, Prakash V, Taggart M, Bekker L, Das D, Diekmann J, Diekmann M, Killian E, Meharg A, Patra RC, Saini M, Wolter K (2006). "Removing the threat of diclofenac to critically endangered Asian vultures". PLoS Biol 4 (3): e66. doi:10.1371/journal.pbio.0040066. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16435886.  

External links

© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
 Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic