Indomethacin acetylsalicylic acid

It is now a well-known fact that nonsteroidal anti-inflammatory agents such as acetylsalicylic acid, indomethacin, and ibuprofen are potent, irreversible inhibitors of fatty acid cyclooxygenase. Furthermore, significant evidence has appeared in the literature that indicates that steroidal antiinflammatory agents may prevent the release of arachidonic acid from the more complex lipids to which it is normally attached. 

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. 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory drugs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsalicylic acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, tS)-<8) and (/ )-(9) ibuprofen, (S)-(10) and (/ )-(11), flurbiprofen naproxen, and fenoprofen. See also Analgesics, Antipyretics, and Antiinflammatory Agents and Salicylic Acid and Related Compounds. 

Most of the drugs that inhibit cyclooxygenase do inhibit both Cox-1 and Cox-2 this applies to drugs such as diclofenac, indomethacine, and acetylsalicylic acid. More recent developments have led to selective inhibitors of Cox-... 

Cross reactivity (S22I) At a concentration of 1000 mg/1 in serum the following compounds increased the apparent value for a 30 mg/1 phenobarbital control by < 20% acetaminophen, acetylsalicylic acid, caffeine, carbamazep-ine, diazepam, ethosuximide, fluphenazine, hexabarbital, indomethacin, meprobamate, methaqualone, methsuximide, methyprylon, phenylbutazone, phensuximide, theophylline, and valproic acid. 

Berg KJ. Acute effects of acetylsalicylic acid on renal function in normal man. Eur J Clin Pharmacol 1977 11 117-123. Donker AJ, Arisz L, Brentjens JR, van der Hem GK, Hollemans HJ. The effect of indomethacin on kidney function and plasma renin activity in man. Nephron 1976 17 288-296. 

Various NSAIDs, such as ibuprofen, indomethacin, ketoprofen, phenylbutazone, piroxicam, and oxyphenbutazone, can decrease renal creatinine and lithium clearance by their common inhibitory action on prostaglandin synthesis. Aspirin (acetylsalicylic acid) and sulindac have not been found to increase lithium plasma steady-state concentrations. ... 

Kaldestad E, Hansen T, Bradi HK. Interaction of indomethacin and acetylsalicylic acid as shown by the serum concentrations of indomethacin and salicylate. EurJ Clin Pharmacol (1975) 9,199-207. 

Light, R.B., (1986). Indomethacin and acetylsalicylic acid reduce intrapulmonary shunt in experimental pneumococcal pneumonia. Am. Rev. Respir. Dis., 134, 520-525... 

The NIICRs to benzoic acid, cinnamic acid, cinnamic aldehyde, methyl nicotinate and diethyl fuma-rate can be inhibited by peroral acetylsalicylic acid and indomethacin (Lahti et al. 1983, 1987) and by a topical application of diclofenac or naproxen gels (Johansson and Lahti 1988). The duration of inhibition by a single dose of acetylsalicylic acid can be as long as 4 days (Kujala and Lahti 1989). The mechanism by which non-steroidal anti-inflammatory drugs inhibit NIICRs in human skin has not been defined, but it is probably ascribable to the inhibition of prostaglandin metabolism. 

Examples of substances that are prone to hydrolysis are acetylsalicylic acid, ampicillin, barbiturates, chloramphenicol, chlordiazepoxide, cocaine, corticosteroid phosphate or succinate esters, proteins, folinic acid, indomethacin, local anaesthetics, paracetamol (acetaminophen), pilocarpine, tropa alkaloids (atropine, scopolamine), xylomethazoline and the antimicrobial preservatives methyl and propyl parahydroxybenzoate. In the field of oncology, melphalan and bendamustine hydrochloride are highly susceptable to hydrolysis with a shelf life of 1.5 h for melphalan and 3.5 h for bendamustine at room temperature. 

Most antiinflammatory drugs, for instance acetylsalicylic acid, phenylbutazone, indomethacin, cortison, flufenaminic acid etc. are inhibitors of sulfate metabolism in connective tissue (2). These antiinflammatory drugs are inhibitors of oxydative phosphorylation and therefore in presence of these substances the content of tissue ATP and its reaction product with sulfate 3 -phosphoadenylylsulfate is decreased. 

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