Indomethacin adverse effects

Indomethacin was used traditionally, but its relative cyclooxygenase-1 (COX-1) selectivity theoretically increases its gastropathy risk. Thus other generic NSAIDs may be preferred. Adverse effects of NSAIDs include gastropathy (primarily peptic ulcers), renal dysfunction, and fluid retention. NSAIDs generally should be avoided in patients at risk for peptic ulcers, those taking warfarin, and those with renal insufficiency or uncontrolled hypertension or heart failure. 

Pharmacotherapy. Acute relief of inflammatory symptoms can be achieved by prostaglandin synthase inhibitors nonsteroidal anti-inflammatory drugs, or NSAlDs, such as diclofenac, indomethacin, piroxicam, p. 200), and glucocorticoids (p. 248). The inevitably chronic use of NSAlDs is likely to cause adverse effects. Neither NSAlDs nor glucocorticoids can halt the progressive destruction of joints. 

Naproxen (Naprosyn) also has pharmacological properties and clinical uses similar to those of ibuprofen. It exhibits approximately equal selectivity for COX-1 and COX-2 and is better tolerated than certain NSAIDs, such as indomethacin. Adverse reactions related to the GI tract occur in about 14% of all patients, and severe GI bleeding has been reported. CNS complaints (headache, dizziness, drowsiness), dermatological effects (pruritus, skin eruptions, echinoses), tinnitus, edema, and dyspnea also occur. 

Adverse effects may be severe with abdominal pain, vomiting and diarrhoea which may be bloody. Renal damage may result and rarely, blood disorders. Large doses cause muscle paralysis. Many patients are unable to tolerate colchicine and use NSAIDs such as indomethacin or diclofenac for an acute attack of gout some patients require oral corticosteroid. 

Adverse effects are uncommon, apart from excess of therapeutic effect (electrolyte disturbance and hypotension due to low plasma volume) and those mentioned in the general account for diuretics (below). They include nausea, pancreatitis and, rarely, deafness which is usually transient and associated with rapid i.v. injection in renal failure. NSAIDs, notably indomethacin, reduce frusemide-induced diuresis probably by inhibiting the formation of vasodilator prostaglandins in the kidney. 

Typical gastrointestinal adverse effects with naproxen occur at approximately the same frequency as with indomethacin, but perhaps with less severity. CNS side effects range from drowsiness, headache, dizziness, and sweating, to fatigue, depression, and ototoxicity. Less common reactions include pruritus and a variety of dermatological problems. A few instances of jaundice, impairment of renal function, angioedema, thrombocytopenia and agranulocytosis have been reported. 

A high percentage (35-50%) of patients receiving usual therapeutic doses of indomethacin experience untoward symptoms, and -20% must discontinue its use because of the side effects. Most adverse effects are dose-related. 

Ibuprcfen is thought to be better tolerated than aspirin and indomethacin and has been used in patients with a history of gastrointestinal intolerance to other NSAIDs. Nevertheless, 5-15% of patients experience GI side effects. Less frequent adverse effects include thrombocytopenia, rashes, headache, dizziness, blurred vision, and in a few cases toxic amblyopia, fluid retention, and edema. Patients who develop ocular disturbances should discontinue the use of ibuprofen. Ibuprofen can be used occasionally by pregnant women however, the concerns apply regarding third-trimester effects. Excretion into breast milk is thought to be minimal, so ibuprofen also can he used with caution by women who are breastfeeding. 

Typical Gl adverse effects with naproxen occur at approximately the same frequency as with indomethacin, but perhaps with less severity. CNS side effects range from drowsiness, headache,... 

Ellison NM, Servi RJ. Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU a possible adverse effect due to concomitant indomethacin administration. Cancer Treat Rep (1985) 69,342-3. 

In addition to their adverse effects on the skin barrier properties, surfactants also are used to enhance the penetration of active ingredients into the skin [149]. When used in this fashion, the surfactant is known as a penetration enhancer. Of the three classes of surfactants, the nonionics, because of their low irritancy potential, have received the most attention. However, Maibach and co-workers [150,151] have investigated the effects of sodium lauryl sulfate on the percutaneous absorption of hydrocortisone, indomethacin, ibuprofen, and acitretin. 

Of course, none of this was known in 1897 when aspirin was first synthesised or indeed even earlier where it had long been recognised that extracts of willow bark had anti-inflammatory properties. Aspirin soon entered into clinical use and it was followed by other compounds such as indomethacin. The first adverse effects to become apparent were those on the gastrointestinal system. 

Additional mechanisms of action of indomethacin suggested are the inhibition of leukocyte migration and antagonism of capillary constriction.- Like other ajrti-inflammatory agents it possesses moderate auitil3miphocytic properties in vitro, but no adverse effect on the host-resistance of experimental animals. 9... 

When the drug and the CD are both charged, electrostatic effects may be observed. Adverse electronic effects have been observed for the complexation between the anionic form of indomethacin and the dianion of carboxymethyl-p-CD, CM2-p-CD.At pH 6.6, indomethacin exists as an anion and under these conditions, the anionic carboxymethyl CD did not complex the drug at all, probably due to electrostatic repulsions. However, the tri-anion, CM3-p-CD l has been reported to complex the anionic forms of warfarin and indomethacin (Table 5) although only at 71 and 60% of the binding observed for the neutral p-CD. 

NSAIDs (nonsteroidal antiinflammatory drugs) Isolated cases of adverse neurological side effects have been seen with naproxen or phenylbutazone given with misoprostol. Misoprostol also increases the abdominal pain and other side effects of diclofenac and indometacin (indomethacin). Paracetamol (acetaminophen) intensifies pain if given with mifepristone and sulprostone used to induce abortion. 

Whereas the toxicity of sulindac is lower than that observed for indomethacin and other NSAIDs, the spectrum of adverse reactions is very similar. The most frequent side effects reported are associated with irritation of the Gl tract (e.g., nausea, dyspepsia, and diarrhea), although these effects generally are mild. Effects on the CNS (e.g., dizziness and headache) are less common. Dermatological effects are less frequently encountered. 

Gastrointestinal disturbances are the most frequent side effects of indomethacin. Endoscopic examination of the stomach in healthy volunteers taking 100 mg of indomethacin daily for 7 days revealed extensive gastritis with submucosal haemorrhages, oedema, and erosions (35 ). Of 1261 adverse reactions to indomethacin reported to the U.K, Committee on Safety of Medicines, there were 121 instances of gastrointestinal bleeding with 25 fatalities (21 ). 

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