Nonsteroidal anti-inflammatory drugs for osteoarthritis

Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis The CLASS study A randomized, controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000 284 1247-1255. 

K. M. Verburg, and G. S. Geis. 2000. Gastrointestinal Toxicity with Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis The CLASS Study A Randomized Controlled Trial. JAMA 284 1247-1255. 

The salicylates and nonsteroidal anti-inflammatory drug (NSAIDs) are important in the treatment of arthritic conditions. For example, the salicylates and NSAIDs are used in the treatment of rheumatoid arthritis (a chronic disease characterized by inflammatory changes within the body s connective tissue) and osteoarthritis (a noninflammatory joint disease resulting in degeneration of the articular cartilage and... 

COX-2 Inhibitor Celecoxib (Celebrex, Pfizer) inhibits the enzyme COX-2, which is involved in pain and inflammation, but it has no effect on the COX-1 enzyme, which helps to maintain stomach lining. It is prescribed for the relief of pain and symptoms of osteoarthritis and rheumatoid arthritis. Previously, nonsteroidal anti-inflammatory drugs (NSAIDs) were used. NSAIDs inhibit both COX-1 and COX-2 enzymes and cause stomach bleeding (see Case Study 2). 

As was already mentioned, piroxicam also is a nonsteroidal, anti-inflammatory drug. It is used in inflammatory and degenerative diseases of the musculoskeletal system that are accompanied by painful symptoms. It is used for rheumatic heart disease, nonspecific infectious polyarthritis, gouty arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, arthrosis, back pain, nenralgia, myalgia, and other diseases associated with inflammation. Synonyms for piroxicam are feldene, dexicam, roxenan, and others. 

Nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcers For reducing the risk of NSAID-associated gastric ulcers in patients with a history of documented gastric ulcer who require the use of an NSAID for treatment of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. 

Clinical use Diflunisal (Brogden et al., 1980) is a nonsteroidal anti-inflammatory drug used in the treatment of mild to moderate pain including osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea. It is used as base or lysine- or arginine-salt for oral or parenteral application. 

Clinical use Ibuprofen (Busson, 1986) is a nonsteroidal anti-inflammatory drug, commonly used for the treatment of mild to moderate pain. It is used in conditions like rheumatoid arthritis, osteoarthritis, joint and soft tissue pain, dental pain, postoperative pain, dysmenorrhoea and headache, including acute migraine attacks. 

Clinical use Ketoprofen (Hommeril et al., 1994) is a nonsteroidal anti-inflammatory drug used for the treatment of a variety of acute and chronic pain and inflammatory conditions including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, postoperative pain and dysmenorrhoea. It is given by oral, rectal, topical or intramuscular application (100-200 mg/day, maximal dose 300 mg/day) as the sodium or lysine salt. 

Pincus T, Swearingen C, Cummins R et al. Preference for nonsteroidal anti-inflammatory drugs versus acetaminophen and concomitant use of both types of drugs in patients with osteoarthritis. J Rheumatol 2000 27 ... 

As a model nonsteroidal anti-inflammatory drug ibuprofen was chosen. It is very effective for the systemic treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is almost insoluble in water (1.74 x IQ- mol L ) [30], while its solubility in IPM is 0.160 + O.OlSg mL [31]. As a weak acid (pK = 4.4) its solubility increases with increasing pH. Ibuprofen shows a considerable surface activity [32] that could contribute to its enhanced permeation through biological membranes [33]. The release profiles of tested ME samples are shown in Figure 10.10a. 

Synthesis of Sulindac Sulindac 23 is a nonsteroidal anti-inflammatory drug mainly used in the treatment of pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and acute gouty arthritis. More recently, it attracted also the attention of the scientists for its anticancer effects. It used to be sold in its racemic form, but its enantiopure preparation was known since 2001. The... 

Piroxicam is a nonsteroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis and osteoarthritis [97]. The solubility of piroxicam is low, with the maximum concentration reached after more than 2 h from the oral administration. The piroxicam forms three known polymorphs and a hydrate. In all these forms piroxicam is present as a neutral, nonionized, species (Scheme 13.15, left) [98]. As the cocrystallization with suitable pharmaceutical coformers is a standard method for improving the physicochemical properties of drugs, piroxicam has naturally been selected as a target for such studies [99,100]. It was shown that some cocrystalline forms with carboxylic acids were yellow and that the piroxicam in these compounds was present as a zwitterion, similarly as in previously reported hydrate or inclusion compound with beta-cyclodextrin [101]. 

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