NSAIDs side effects

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

The first two selective COX-2 inhibitors to be marketed and subjected to in depth clinical trials were celecoxib and rofecoxib. Both compounds are as effective as standard NSAIDs in rheumatoid arthritis, osteoarthritis and for pain following orthopaedic or dental surgery. Gastrointestinal side effects were far fewer than with comparator diugs and in fact were no... 

It follows that drugs that selectively inhibit COX-2 should cause fewer side effects than those that inhibit both COX-1 and COX-2. At therapeutic doses, all currently available NSAIDs, with the excqrtion of celecoxib, etoricoxib, lumiracoxib and parecoxib (the prodrug of valdecoxib), are non-selective and inhibit both COX isoforms. 

Indomethacin treatment is associated with a high incidence (30%) of side effects typical for those seen with other NSAIDs (see above). Gastrointestinal side effects, in particular, are more frequently observed after indomethacin than after administration of other NSAIDs. The market share of indomethacin ( 5%) is therefore low compared to that for other non-steroidal anti-rheumatic agents. 

Ibuprofen is the most thoroughly researched 2-ary lpropionic acid. It is a relatively weak, non-selective inhibitor of COX. In epidemiological studies, ibuprofen compared to all other conventional NSAIDs, has the lowest relative risk of causing severe gastrointestinal side effects. Because of this, ibuprofen is the most frequently used OTC ( over the counter , sale available without prescription) analgesic. Ibuprofen is highly bound to plasma proteins and has a relatively short elimination half-life ( 2 h). It is mainly glucuronidated to inactive metabolites that are eliminated via the kidney. 

The indications for these agents are in principle identical to those of the non-selective NSAIDs although the substances have not yet received approval for the whole spectrum of indications of the conventional NSAIDs. Because they lack COX-1-inhibiting properties, COX-2-selective inhibitors show fewer side effects than conventional NSAIDs. However, they are not free of side effects because COX-2 has physiological functions that are blocked by the COX-2 inhibitors. The most frequently observed side effects are infections of the upper respiratory tract, diarrhoea, dyspepsia, abdominal discomfort and headache. Peripheral oedema is as frequent as with conventional NSAIDs. The frequency of gastrointestinal complications is approximately half that observed with conventional NSAIDs. 

Many adverse reactions are associated with the use of the NSAIDs. However, many patients take these drag s and experience few, if any, side effects. Some of the adverse reactions associated with the use of these drag s are listed here. 

NSAIDs are more likely to cause GI side effects. The salicylate salts cause fewer GI side effects than aspirin and do not inhibit platelet aggregation. 

Since she is in considerable pain the best alternative for this otherwise physically intact woman is an operation of her knees. In the meantime a supportive knee bandage can help relieve her pain in some way. She must tell her doctor that she is taking NSAIDs and be properly informed of the side effects and how to use the drug. The drug should only be used for short periods and in low doses because of the considerable danger of different side effects. 

The FDA approved this selective cyclooxigenase (COX)-2 inhibitor (Vioxx) for the treatment of pain and inflammation in 1999. This NSAID demonstrated to have a lower risk of side effects such as gastrointestinal ulcers and bleeding than nonse-lective COX inhibitors, for example, ibuprofen. In 2004, a long-term study of Vioxx in patients at increased risk of colon polyps was halted because of an increased cardiovascular risk (heart attack, stroke) in the rofecoxib group. Subsequently, Merck withdrew the drug from the world market at the end of September 2004 [46]. 

Indometacin is an indole acetic acid derivative, while naproxen is a propionic acid derivative. Both are non-steroidal anti-inflammatory drugs (NSAIDs). Indometacin is associated with a higher incidence of side-effects, particularly gastrointestinal as well as headache and dizziness. 

The first-line agents in the treatment of rheumatoid arthritis are non-steroidal anti-inflammatory drugs such as diclofenac. Diclofenac and indometacin, another NSAID, tend to have similar activity hov/ever, indometacin has a higher incidence of side-effects and therefore diclofenac is more appropriate for initial treatment. Sodium aurothiomalate is classified as a disease-modifying antirheumatic drug and is used as a second-line treatment in rheumatoid arthritis, but has been superseded by methotrexate, administered v/eekly. Paracetamol is often indicated in the management of osteoarthritis. Local intra-articular injections of dexamethasone may be administered for the relief of soft-tissue inflammatory conditions. 

Meloxicam is a partially selective cycloHDxygenase-2 inhibitor and is therefore less likely to cause gastrointestinal side-effects, such as bleeding, than other NSAIDs. 

Acetyls alley lie acid was shown to prevent cirrhosis under certain experimental conditions [125]. Naproxen and indomethacin partially protected against LPS and D-galactosamine-in-duced hepatotoxicity [126] Acetylsalicylic acid and ibuprofen were also protective in endo-toxic shock [127]. Endotoxaemia is one of the complications in cirrhotic patients [128] and is probably caused by an impaired ability of the liver to take up and detoxify gut-derived LPS [116]. The presence of portosystemic shunts in cirrhotic patients may also contribute to this spill-over of LPS into the systemic circulation [129]. NSAIDs, however, are also reported to provoke deleterious effects on renal function in cirrhosis [130], and can therefore not be used in cirrhotic patients. Cell-specific delivery of NSAIDs to SECs and/or KCs may make application of these drugs in cirrhosis feasible by circumventing the renal side-effects. 

Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase [2] and consequently the synthesis of most eicosanoids. This explains their analgesic, antipyretic, and antirheumatic effects. Frequent side effects of NSAIDs also result from inhibition of eicosanoid synthesis. For example, they impair hemostasis because the synthesis of thromboxanes by thrombocytes is inhibited. In the stomach, NSAIDs increase HCl secretion and at the same time inhibit the formation of protective mucus. Long-term NSAID use can therefore damage the gastric mucosa. 

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