Kamis, 20 Oktober 2011

CLASSIFICATION OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

1) Carboxylic Acids
            a) Salicylic Acids & Esters
                    Diflunisal
Diflunisal (5-(2,4-difluorophenyl)-2-hydroxy-benzoic acid ) is a generic NSAID (non-steroidal anti-inflammatory drug). It is often used under the brand name Dolobid marketed by Merck & Co. Diflunisal acts by inhibiting the production of prostaglandin, a hormone that creates inflammation and stimulates the neuro receptors for pain. Though diflunisal has an onset of 1 hour, and maximum analgesia at 2 to 3 hours, the diflunisal plasma levels will not be steady until repeated doesages are achieved. 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.
Deaths that have occurred from diflunisal usually involved mixed drugs and or extremely high dosages. 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, thus it is relatively hard to overdose by accident

         b) Acetic Acids
                    i) Phenylacetic Acids
                           Diclofenac
Diclofenac (marketed as Voltaren, Voltarol, Diclon, Dicloflex Difen, Difene, Cataflam, Pennsaid, Rhumalgan, Modifenac, Abitren, Arthrotec and Zolterol, with various drug dose combinations) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and an analgesic reducing pain in conditions such as in arthritis or acute injury. It can also be used to reduce menstrual pain, dysmenorrhea. 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, while in some other countries only as the potassium salt. 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.
Diclofenac is well-tolerated after 30 years' experience by the general human population, but may unexpectedly become intolerated in some of the elderly population of long term users.

                    ii) Carbo- and Hetero-Cyclic Acetic Acids
                           Indomethacin
Indometacin (INN) or Indomethacin (USAN and former BAN) is a non-steroidal anti-inflammatory drug commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms. It is marketed under many trade names, including Indocin, Indocid, Indochron E-R, and Indocin-SR. The name is derived from its chemical name: 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-H-indole-3-acetic acid. Indometacin is a methylated indole derivative and a member of the arylalkanoic acid class of NSAIDs, which includes diclofenac.

                           Sulindac
Sulindac is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIDs, it is useful in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene that is converted in the body to an active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAID's except for drugs of the COX-2 inhibitor class[citation needed]. The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.
Its usual dosage is 150-200 milligrams twice per day, with food. It should not be used by persons with major allergic reactions (urticaria or anaphylaxis) to aspirin or other NSAIDs, and should be used with caution by persons having pre-existing peptic ulcer disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas.
Sulindac is an effective tocolytic and may be used in the treatment of preterm labour. According to the Cautions distributed with this prescription drug from Walgreens, this medicine has been shown to cause harm to the human fetus.
Since it was found, that the sulfoxide functional group can be reduced by methionine sulfoxide reductase A (MsrA), a possible anti-oxidative capability is being discussed.

Tolmetin
Tolmetin (2-[1-methyl-5-(4-methylbenzoyl)-pyrrol-2-yl]acetic acid ) is a non-steroidal anti-inflammatory drug of the arylalkanoic acids. It is used primarily to reduce hormones that cause pain, swelling, tenderness, and stiffness in conditions such as osteoarthritis and rheumatoid arthritis, including juvenile rheumatoid arthritis. In the United States it is marketed as Tolectin and comes as a tablet or capsule.
Tolmetin can increase the risk of heart or circulatory conditions such as heart attacks and strokes. It should not be taken shortly before or after coronary artery bypass surgery.[1] Tolmetin can also increase the risk of gastrointestinal conditions such as perforation or bleeding, which is fatal. Antacids can be taken with tolmetin to relieve stomachaches that often occur.[1] Overdose can result in drowsiness, nausea, epigastric pain, and vomiting.
When tested in rats tolmetin prevented experimentally stimulated polyarthritis and reduced inflammation. In patients with rheumatoid arthritis or osteoarthritis tolmetin restrained disease activity as efficiently as aspirin and indometacin, although the occurrence of mild gastrointestinal adverse effects and tinnitus was lower in patients treated with tolmetin than it was with aspirin-treated patients and the occurrence of adverse effects of the central nervous system was lower with tolmetin than it was with indometacin.[2]
Although the mechanism of action of tolmetin is unknown, research involving humans and animals has shown that tolmetin does not achieve anti-inflammatory response by stimulation of the adrenal or pituitary gland, but it has shown tolmetin restrains prostaglandin synthetase in vitro and reduces plasma of prostaglandin E, possibly causing the anti-inflammatory response

 c) Propionic Acids
      Ketoprofen
Ketoprofen, (RS)2-(3-benzoylphenyl)-propionic acid (chemical formula C16H14O3) is one of the propionic acid class of non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin.
Ketoprofen was available over-the-counter in the United States in the form of 12.5 mg coated tablets (Orudis KT®), but the product has been discontinued. It is available by prescription as 25, 50, 75, 100, 150, and 200 mg capsules.
Ketoprofen also comes in a 2,5% gel for topical application.
Brand names in the US are Orudis and Oruvail. It is available in the UK as Ketoflam and Oruvail, and in France as Bi-Profénid. Ketoprofen should not be used in with other NSAIDs or corticorticeriods, as this increases the risk of GI ulceration. It should also be used with caution with other anticoagulants. It is commonly used with omeprazole, sucralfate, and cimetidine to help protect the GI tract.

Tiaprofenic Acid
Tiaprofenic acid (5-Benzoyl-α-methyl-2-thiopheneacetic acid ) is a non-steroidal anti-inflammatory drug of the arylpropionic acid (profen) class, used to treat pain, especially arthritic pain. The typical adult dose is 300mg twice daily. It is not recommended in children.
It is sparingly metabolised in the liver to two inactive metabolites. Most of the drug is eliminated unchanged in the urine. Renal disease impairs excretion, and it should be used with caution in renal disease.
Longterm use of tiaprofenic acid is associated with severe cystitis, roughly 100 times more commonly than other NSAIDs. It is contraindicated in patients with cystitis and urinary tract infections.
It is marketed under the trade names Surgam, Surgamyl and Tiaprofen, and in generic formulations. A sustained-release preparation is available.

Ibuprofen
Ibuprofen (2-[4-(2-methylpropyl)phenyl]propanoic acid ) (from the earlier nomenclature iso-butyl-propanoic-phenolic acid) is a non-steroidal anti-inflammatory drug (NSAID) originally marketed as Nurofen and since then under various other trademarks (See tradenames section). It is used for relief of symptoms of arthritis, primary dysmenorrhea, fever, and as an analgesic, especially where there is an inflammatory component. Ibuprofen has no antiplatelet (blood-thinning) effect.
Low doses of ibuprofen (200 mg, and sometimes 400 mg) are available over the counter (OTC) in most countries. Ibuprofen has a dose-dependent duration of action of approximately 4–8 hours, which is longer than suggested by its short half-life. The recommended dose varies with body mass and indication. Generally, the oral dose is 200–400 mg (5–10 mg/kg in children) every 4–6 hours, adding up to a usual daily dose of 800–1200 mg. 1200 mg is considered the maximum daily dose for over-the-counter use, though under medical direction, a maximum daily dose of 3200 mg may sometimes be used in increments of 600–800 mg.
Ibuprofen is also available in topical form, and is absorbed through the skin, and can be used for sports injuries, with much less risk of gastrointestinal problems.

Nproxen
Naproxen (INN) (pronounced /nəˈprɒksən/) is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of moderate to severe pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury (like fractures), menstrual cramps, tendinitis, bursitis, and the treatment of primary dysmenorrhea. Naproxen and naproxen sodium are marketed under various trade names including: Aleve, Anaprox, Miranax, Naprogesic, Naprosyn, Naprelan, Synflex.
Naproxen was first and originally marketed as the prescription drug Naprosyn in 1976 and naproxen sodium was first marketed under the trade name Anaprox in 1980. It remains a prescription-only drug in much of the world. The U.S. Food and Drug Administration (FDA) approved the use of naproxen sodium as an over-the-counter (OTC) drug in 1994, where OTC preparations are sold under the trade name Aleve. In Australia, small packets of lower-strength preparations of naproxen sodium are Schedule 2 Pharmacy Medicines.
Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs. It is an odorless, white to off-white crystalline substance. It is lipid-soluble and practically insoluble in water. It has a melting point of 153 °C.

2) Enolic Acids
         a) Pyrazolones
Phenylbutazone
Phenylbutazone, often referred to as bute, is a crystalline substance having the structure shown at right.
·                        Structural name: 4-butyl-1,2-diphenyl-3,5-pyrazolidinedione
·                        Chemical formula: C19H20N2O2
Oxyphenbutazone, the major metabolite of phenylbutazone, differs only in the para location of one of its phenyl groups, where a hydrogen atom is replaced by a hydroxyl group (making it 4-butyl-1-(4-hydroxyphenyl)-2-phenyl-3,5-pyrazolidinedione).
Despite its name, phenylbutazone is chemically unrelated to the class of chemicals known as benzones (common examples include oxybenzone, dioxybenzone, avobenzone, and sulisobenzone), which are used as active ingredients in sunscreen formulations for protection against UVB rays.
Phenylbutazone is used as a non-steroidal anti-inflammatory drug (NSAID) for the treatment of chronic pain, including the symptoms of arthritis. Its use is limited by such severe side effects as suppression of white blood cell production and aplastic anemia.

         b) Oxicams
Piroxicam
Piroxicam (marketed in the U.S. under the trade name Feldene) is a non-steroidal anti-inflammatory drug used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; and act as an analgesic, especially where there is an inflammatory component. It is also used in veterinary medicine to treat certain neoplasias expressing cyclooxygenase (COX) receptors, such as bladder, colon, and prostate cancers.
Other brand names for Piroxicam include "Brexin," "Erazon," "Felden", "Feldoral," "Hotemin," "Pirox von ct," "Proponol," "Reumador," "Veral," and "Vurdon."


3) Cox II Inhibitors
                       Celecoxib
Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl) pyrazol-1-yl]benzenesulfonamide ) is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra. Celecoxib is available by prescription in capsule form.
Celecoxib is licensed for use in osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce the number of colon and rectal polyps in patients with familial adenomatous polyposis. It was originally intended to relieve pain while minimizing the gastrointestinal adverse effects usually seen with conventional NSAIDs. In practice, its primary indication is in patients who need regular and long term pain relief: there is probably no advantage to using celecoxib for short term or acute pain relief over conventional NSAIDs. In particular, the pain relief offered by celecoxib is similar to that offered by paracetamol
Valdecoxib
Valdecoxib (4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide ) is a prescription drug used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is classified as a nonsteroidal anti-inflammatory drug, or NSAID, and should not be taken by anyone allergic to these types of medications.
Valdecoxib was manufactured and marketed under the brand name Bextra by G. D. Searle & Company. It was approved by the United States Food and Drug Administration on November 20, 2001, and was available by prescription in tablet form until 2005, when it was removed from the market due to concerns about possible increased risk of heart attack and stroke.

                       Meloxicam
 Meloxicam ((8E)-8-[hydroxy-[(5-methyl-1,3-thiazol-2-yl)amino]methylidene]-9-methyl-10,10-dioxo-10λ6-thia-9-azabicyclo[4.4.0]deca-1,3,5-trien-7-one ) is a nonsteroidal anti-inflammatory drug used to relieve the symptoms of arthritis, primary dysmenorrhea, fever; and as an analgesic, especially where there is an inflammatory component. It has been developed by Boehringer-Ingelheim. It is closely related to piroxicam.
In Europe it is marketed under the brand names Movalis, Melox, and Recoxa. In the U.S. it is generally marketed under the brand name Mobic, in Canada as Mobicox. In Latin America, the drug is marketed as Tenaron.

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