Indometacin (INN and BAN) or indomethacin (AAN, USAN, and former BAN) is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. Indomethacin has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of Indometacin, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Indomethacin concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. Indometacin is indicated for: Moderate to severe rheumatoid arthritis including acute flares of chronic disease, Moderate to severe ankylosing spondylitis, Moderate to severe osteoarthritis, Acute painful shoulder (bursitis and/or tendinitis), Acute gouty arthritis. In general, adverse effects seen with indomethacin are similar to all other NSAIDs. For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, it inhibits the production of prostaglandins in the stomach and intestines, which maintain the mucous lining of the gastrointestinal tract. Indometacin, therefore, like other non-selective COX inhibitors can cause peptic ulcers. These ulcers can result in serious bleeding and/or perforation requiring hospitalization of the patient. To reduce the possibility of peptic ulcers, indomethacin should be prescribed at the lowest dosage needed to achieve a therapeutic effect, usually between 50–200 mg/day. It should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. highly dosed antacids, ranitidine 150 mg at bedtime, or omeprazole 20 mg at bedtime). Other common gastrointestinal complaints, including dyspepsia, heartburn and mild diarrhea are less serious and rarely require discontinuation of indomethacin.

Rofecoxib is a nonsteroidal anti-inflammatory drug which selectively inhibits COX-2 and subsequent prostaglandin synthesis. The drug was developed by Merk and approved by FDA in 1999 for relief of signs and symptoms of arthritis, acute pain in adults, and painful menstrual cycles under the name Vioxx. Later on Merck voluntarily withdrawn Vioxx from the market due to safety concerns (high risk of heart attack and stroke).

Suprafen is a dual inhibitor of COX-1 and COX-2, which was used for the inhibition of intraoperative miosis. Suprafen was marketed under the name Profenal, however, it is no longer available in the USA.

BENOXAPROFEN is an anti-inflammatory drug indicated for the treatment of arthritis. It was marketed under the brand name ORAFLEX® in the US and as OPREN® in Europe by Eli Lilly and Company. In 1982 Eli Lilly voluntarily withdrew BENOXAPROFEN from the market due to postmarketing reports of severe liver toxicity in patients who took it.

Oxyphenbutazone is a non-steroidal anti-inflammatory drug, cyclooxygenase (prostaglandin synthetase) inhibitors which was marked under brand name tandearil for the treatment rheumatic disorders such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis. But this drug was withdrawn from markets due to bone marrow suppression.

Aurothioglucose (trade name Solganal), also known as gold thioglucose, is a glucose derivative formerly used to treat rheumatoid arthritis, that cannot be adequately controlled by other medicines. Aurothioglucose has been shown to inhibit protein kinase C, a metalloenzyme containing Zn(2+) bound to cysteine and histidine residues, which plays a crucial role in intracellular signal transduction by phosphorylating serine/threonine residues in the protein. The inhibition of protein kinase C has been suggested as a possible mode of action for the therapeutic antirheumatic action of gold drugs. In 2001, aurothioglucose was withdrawn from the Dutch market, where it had been the only injectable gold preparation available since 1943, forcing hospitals to change medication for a large number of patients to aurothiomalate. The drug had been in use for more than 70 years, and four years later the reasons for its sudden disappearance remained unclear.

Oxaceprol, a structural analog of hydroxyproline, has been used for several years for the treatment of osteoarthritis and rheumatoid arthritis, showing good gastrointestinal safety, particularly in comparison with NSAIDs. It was shown that oxaceprol does not inhibit the synthesis of prostaglandins in vitro, but acts predominantly by inhibiting leukocyte adhesion and migration, thus inhibiting inflammation at an early stage and helps in pain relief.

Glucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, as well as the cell walls of fungi and many higher organisms. Glucosamine is one of the most abundant monosaccharides. It is produced commercially by the hydrolysis of crustacean exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat. Oral glucosamine is a dietary supplement and is not a pharmaceutical drug. It is illegal in the US to market any dietary supplement as a treatment for any disease or condition. Glucosamine is marketed to support the structure and function of joints, and the marketing is targeted to people suffering from osteoarthritis. Commonly sold forms of glucosamine are glucosamine sulfate, glucosamine hydrochloride, and N-acetylglucosamine. Of the three commonly available forms of glucosamine, only glucosamine sulfate is given a "likely effective" rating for treating osteoarthritis. Glucosamine is often sold in combination with other supplements such as chondroitin sulfate and methylsulfonylmethane. Glucosamine, along with commonly used chondroitin, is not routinely prescribed to treat people who have symptomatic osteoarthritis of the knee, as there is insufficient evidence that this treatment is helpful. One clinical study over three years showed that glucosamine in doses of 1500 mg per day is safe to use. Glucosamine with or without chondroitin elevates the international normalized ratio (INR) in individuals who are taking the blood thinner, warfarin. It may also interfere with the efficacy of chemotherapy for treating cancer symptoms. Adverse effects may include stomach upset, constipation, diarrhea, headache, and rash. There are case reports of people who have chronic liver disease and a worsening of their condition with glucosamine supplementation. Glucosamine is naturally present in the shells of shellfish, animal bones, bone marrow, and fungi. D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars. Specifically in humans, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and glutamine by glutamine—fructose-6-phosphate transaminase as the first step of the hexosamine biosynthesis pathway. The end-product of this pathway is uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is then used for making glycosaminoglycans, proteoglycans, and glycolipids. As the formation of glucosamine-6-phosphate is the first step for the synthesis of these products, glucosamine may be important in regulating their production; however, the way that the hexosamine biosynthesis pathway is actually regulated, and whether this could be involved in contributing to human disease remains unclear.

Acemetacin is a non-steroidal anti-inflammatory drug used for the treatment of osteoarthritis, rheumatoid arthritis, lower back pain, and relieving post-operative pain. It is manufactured by Merck KGaA under the tradename Emflex and is available in the UK as a prescription-only drug. Other brand names for acemetacin include Rheutrop (Austria), Acemetadoc, Acephlogont, Azeat, Rantudil (Germany, Hungary, Mexico, Portugal, Turkey), Gamespir (Greece), Oldan, Reudol (Spain), Tilur (Switzerland), Ost-map (Egypt). Acemetacin is a glycolic acid ester of indomethacin. The pharmacological activity resulting from acemetacin administration in man is derived from the presence of both acemetacin and indomethacin. The precise pharmacological mode of action of acemetacin is not known. However, unlike other NSAIDs, acemetacin is only a relatively weak inhibitor of prostaglandin synthetase. Prostaglandins are known to have an antisecretory and cytoprotective effect on the gastric mucosa. Acemetacin shows activity in many of the established in vitro tests of anti-inflammatory activity including inhibition of the release of a number of mediators of inflammation. Acemetacin is well absorbed after oral administration. Its major metabolite is indomethacin, which, after repeated administration is present at levels in excess of those of acemetacin. Acemetacin is bound to plasma protein to a slightly lesser extent than indomethacin and has a relatively short plasma elimination half-life. It is eliminated by both hepatic and renal mechanisms. The pharmacokinetics appear to be linear at recommended therapeutic doses, unaffected by moderate renal or hepatic impairment, and unchanged in the elderly.

Alclofenac (Preservex) is a non-steroidal anti-inflammatory agent advocated for use in rheumatoid arthritis, degenerative joint disease and ankylosing spondylitis. Aceclofenac has little pharmacological activity itself; its main mode of action is through its metabolites which include diclofenac and 4’-hydroxy diclofenac. Skin rash is the most frequent side-effect, which in a small proportion of affected patients may be associated with systemic effects. A cutaneous reaction appears to be more likely in patients with a history of previous allergy to penicillin and other drugs. In June 2013 was told about the new contraindications and warnings for diclofenac. This was after a review by European regulators concluded that the risk of arterial thrombotic events (myocardial infarction; stroke) with diclofenac is greater than with other non-selective NSAIDs and similar to the COX-2 inhibitors.