Indo - Indomethacin

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Pretreatment of rats v iihAronia melanocarpa fruit juice (5, 10, and 20mL/kg), which is rich in anthocyanins, decreased gastric lesions caused by indomethacin (Valcheva-Kuzmanova et ah, 2005). Indo-methacin-induced gastric mucosal damage in the rat was accompanied by the development of oxidative stress as evidenced by the accumulation of malondialdehyde. 

Friedman Z, Whitman V, Maisels MJ, Berman W Jr, Marks KH, VeseU ES. Indomethacin disposition and indo-methacin-induced platelet dysfunction in premature infants. J Clin Pharmacol 1978 18(5-6) 272-9. 

A In this patient with well-documented CAD who is sip CABG, either terbutaline or nifedipine would be contraindicated. It is not entirely clear which would be the safest, but based on studies, the use of nifedipine in patients with documented CAD can lead to an increase in mortality. Of the other three, the next most dangerous medication is likely to be MgS04, which can lead to cardiopulmonary arrest at toxic levels. The safest choice between indo-methacin and the oxytocin antagonist is difficult to sort out. Indomethacin has a higher risk characterization at baseline than the oxytocin antagonist, and in a patient with CAD, there should be concerns about renal function which is an issue with NSAIDs. 

High (1-5 mM) concentrations of indo-methacin and other nonsteroidal anti-inflammatory agents reportedly denature P450 enzymes because of their surfactant properties. The loss of P450 content seen when indomethacin is added to liver microsomes is paralleled by essentially stoichiometric appearance of a P420 peak. 

Stenmark, K.R., Fasules, J.W., Morris, K.G., Voelkel, N.F. and Reeves, J.T. (1986). Diethylcarbamazine (DEC) but not indomethacin (INDO) prevents the early lung leak and late pulmonary hypertension in monocrotaline treated rats. Am. Rev. Respir. Dis., 133, A277 (Abstract)... 

Figure 5.9 Effect of glucan on survival time in rats subjected to acute faecal peritonitis (LDjoo)- Glucan (40 mg kg i.p., for 5 days prior) decreased survival time p < 0.001) compared with shock controls. Indomethacin (Indo), 10 mg kg ip. 30 min before peritonitis improved survival time p < 0.001) compared with glucan-treated and shock control groups. From Wise et al, with permission...

Indomethacin (INDO) is a potent and non-selective inhibitor of both cyclooxygenase isoforms (COX-1 and COX-2) that exhibits slow, tight-binding and functionally irreversible inhibition/binding kinetics. 

Figure 4. Attenuation oforoxylin A-induced Vasorelaxation by potassium channel blockers 4-AP andIBTEeicosatriyonic acid (ETI, 10 pM), 4-aminopyridine (4-AP, 10 mM), glipizide (GLP, 30 pM), miconazole (MCN, 5 pM), indomethacine (INDO, 30 pM), N-nitro-L-arginine (L-NNA, 60 pM), iberiotoxin (IBT, lOOng/mL).

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