Gastrointestinal toxicity

Bombardier C, Laine L, Reicin A et al (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl JMed 343 1520-1528... 

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

Elucidation of the activities of individual COX isoforms led to the development of drugs that selectively inhibit the inducible form of the enzyme, COX-2. Thus COX-2 inhibitors were expected to minimize NSAID gastrointestinal toxicity and antiplatelet effects (see Fig. 55-3).19 A common misconception is that COX-2 inhibitors are more effective than nonselective NSAIDs in relieving pain and inflammation. In clinical trials, patients experienced similar levels of pain relief with COX-2 inhibitors and nonselective NSAIDs. 

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. 

List the nonhematologic toxicity to high-dose chemotherapy used in myeloablative preparative regimens, specifically busulfan-induced seizures, hemorrhagic cystitis, gastrointestinal toxicities, and sinusoidal obstruction syndrome. 

C. A., Sugiyama, Y., Reduced gastrointestinal toxicity following inhibition of the biliary excretion of irinotecan and its metabolites by probenecid in rats, Pharm. Res. 2002, 19, 1342-1350. 

Field First Aid Decontaminate At Once for All Exposed Victims Although sulfur mustards cause cellular changes within minutes of contact, the onset of pain and other clinical effects are delayed for one to twenty-four hours. Sulfur mustards are alkylating agents that may cause bone marrow suppression and neurologic and gastrointestinal toxicity. However, the biochemical mechanisms of action are not clearly understood by anyone. The death rate from exposure to sulfur mustard during World War I was 2-3 percent,... 

While rDNA techniques offer exciting possibilities, there are many unanswered questions about the potential toxicity that each new product represents. For example, acute clinical toxicities of interferons (IFNs) include flu-like syndrome, fever, chills, malaise, anorexia, fatigue, and headache. Chronic dose-limiting toxicities include neutropenia, thrombocytopenia, impairment of myeloid maturation, reversible dose-related hepatotoxicity, some neurological toxicity (stupor, psychosis, peripheral neuropathy) and gastrointestinal toxicity. Some of these toxicities would be difficult to ascertain in rodents, and, in fact, may be species-specific. 

No information was located regarding the gastrointestinal toxicity of chlordecone in humans. Only very limited evidence of gastrointestinal effects has been observed in oral studies in experimental animals (Fujimori et al. 1983 Larson et al. 1979b). Thus, it is unlikely that chlordecone exposure would result in adverse effects on the gastrointestinal tracts of persons exposed to low levels at hazardous waste sites. 

Target organs of chloroform toxicity are the central nervous system, liver, and kidneys (see Section 2.2). Respiratory, cardiovascular, and gastrointestinal toxic effects have also been reported. Studies in animals also indicated that chloroform exposure may induce reproductive and developmental effects and cause cancer. Several studies investigated the possible mechanism for chloroform-induced toxicity (see Section 2.5). Proposed mechanisms of chloroform toxicity and potential mitigations based on these mechanisms are discussed below. The potential mitigation techniques mentioned are all experimental. 

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

Flufenamic acid is used for moderate pain and dysmenorrhea, but it should not be used for more than 1 week due to the possibility of nephrotoxicity, gastrointestinal toxicity, and anemia. It is frequently used in combination with the anticoagulant warfarin, the effect of which is strengthened when combined with flufenamic acid. Synonyms for this drug are arlef, flexocutan, romazal, and others. 

Houghton JA, Houghton P, Wooten RS. Mechanism of induction of gastrointestinal toxicity in the mouse by 5-fluorouracil, 5-fluorourdine, and 5-fluoro-2 -deoxyuridine. Cancer Res 1979 39 2406-2413. 

Selective COX-2 inhibitors are ideal agents to combine with chemoradiotherapy for several reasons. First, they have been shown to enhance the effect of various chemotherapeutic agents and radiation on cancer cells. Second, selective COX-2 inhibitors are relatively safe. They do not have severe gastrointestinal toxicity, which is common in many nonselective NSAIDs. For example, celecoxib, a selective COX-2 inhibitor which is currently being used for patients with arthritis, is 375-fold more selective for COX-2 compared to COX-1 (94), and in large randomized, multicenter, placebo-controlled, double-blind trials conducted in patients with rheumatoid arthritis, celecoxib proved to be less toxic than nonselective inhibitors of COX-1 and COX-2, and no more toxic than a placebo (95). Third, high-dose celecoxib (600 mg bid) has no effect on serum thromboxane or platelet function (96). This is obviously important in patients receiving... 

Melarsoprol is a divalent arsenical. It reacts with sulfhydryl groups. Melarsoprol is used for the late stage of sleeping sickness. It has to be administered intravenously. Slow i.v. injection is recommended. It is widely distributed and enters the CNS. It has a very short elimination half-life as it is biotransformed to a pentavalent arsenical. Adverse effects include hypersensitivity reactions and gastrointestinal toxicity causing severe vomiting and abdominal pain. CNS reactions are most serious as the encephalopathy may be fatal. Hemolytic anemia may... 

Garlic bulb Ritonavir Two brief case reports describe gastrointestinal toxic effects in patients taking garlic and ritonavir. 

---