Nonsteroidal anti-inflammatory drugs toxicity

Sung J, Russell RI, Nyeomans, Chan FK, Chen S, Fock K, Goh KL, Kullavanijaya P, Kimura K, Lau C, Louw J, Sollano J, Triadiafalopulos G, Xiao S, Brooks P. Nonsteroidal anti-inflammatory drug toxicity in the upper gastrointestinal tract. J Gastroenterol Hepatol 2000 I5(Suppl) G58-68. 

Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med 1999 340 1888-1899. 

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. 

Mefenamic is a nonsteroidal anti-inflammatory drug used to treat pain, including menstrual pain. Hata et al. [11] treated that drug with P. sordida, and obtained a 90% reduction in mefenamic acid concentration (initial concentration 24 mg L ) after 6 days. The system produced four metabolites, identified as 3 -hydroxymethyl-mefenamic acid, 3 -hydroxymethyl-5-hydroxymefenamic acid, 3 -hydroxmethyl-6 -hydroxymefenamic acid, and 3 -carboxymefenamic acid. Moreover, the authors confirmed that the fungus almost completely removed the acute lethal toxicity of mefenamic towards the freshwater crustacean Thamnocephalus platyurus after 6 days of treatment, suggesting that the metabolites are less toxic than the parental compound. 

Primary hepatocyte cultures have been used as a tool to predict the hepatotoxicity of many compounds such as nonsteroidal anti-inflammatory drugs (Castell et ah, 1988), psychotropic drugs (Boelsterli et ah, 1987), immunosuppressant drugs (Boelsterli et ah, 1988), and salicylates (Tolman et ah, 1978). Rat primary hepatocyte cultures have also been shown to be a good model for examining the mechanisms of metallothionein-induced tolerance to cadmium toxicity (Liu et ah,... 

A recent study showed THC to be toxic to hippocampal neurons, while sparing cortical neurons in concentrations likely to be reached in normal human doses (0.5 pM) (Chan et al. 1998). Apoptotic changes were noted in the hippocampus such as shrinkage of neuronal cell bodies and nuclei as well as DNA strand breaks. THC stimulates release of arachidonic acid, and it was hypothesized that this neurotoxic effect is mediated by cyclooxygenase pathways and free radical generation. In support of this, the toxicity is inhibited by nonsteroidal anti-inflammatory drugs, such as aspirin, and antioxidants such as vitamin E. 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Carson JL, Strom BL, Morse ML, et al. The relative gastrointestinal toxicity of the nonsteroidal anti-inflammatory drugs. Arch Int Med 1987 147 1054. 

Murray M.D. and D.C. Brater (1993). Renal toxicity of the nonsteroidal anti-inflammatory drugs. Annual Reviews of Pharmacology and Toxicology 32 435 65. 

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 glucocorticoids also have powerful anti-inflammatory effects and when first introduced were considered to be the ultimate answer to the treatment of inflammatory arthritis. Unfortunately, the toxicity associated with chronic corticosteroid therapy limits their use except in the control of acute flare-ups of joint disease. Therefore, the nonsteroidal anti-inflammatory drugs have assumed a major role in the long-term treatment of arthritis. 

S.C. Smolinske, et al., Toxic effects of nonsteroidal anti-inflammatory drugs in overdose An overview of recent evidence on clinical effects and dose-response relationship. Drug Safety 5 252-274, 1990. 

Bush TM, Shlotzhauer TL, Imai K (1991) Nonsteroidal anti-inflammatory drugs proposed guidelines for monitoring toxicity. West] Med 155 39-42. 

SJS was for many years considered a severe variant of erythema multiforme major (EMM) however, over the past decade some experts have reclassified SJS as a less severe variant of toxic epidermal necrolysis (TEN) rather than a form of EMM. However, this perspective is not universally accepted. SJS occurs acutely in all ages, with 20% in children and a peak incidence in adults between the second and fourth decades of life. SJS is a potentially fatal disorder with a mortality of approximately 5%.TEN has a mortality rate of approximately 30%. About 50% of cases of these disorders are idiopathic. Identifiable causal factors include microbial infection, particularly with Mycoplasma pneumoniae and HS Vj and medications, including sulfonamides, tetracycline, penicillin, nonsteroidal anti-inflammatory drugs (NSAIDs), psychotropic agents, antiepileptics, and immunizing vaccines. Recent research suggests that HSV infection is a principal fector in the genesis of EMM, whereas medications are a more likely precipitant of SJS and TEN. 

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