Gastrointestinal effects of antipyretic analgesics

Ivey, Kevin J.

doi:10.1016/0002-9343(83)90233-4

Cited by 30 publications

(7 citation statements)

References 67 publications

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“…Indeed, Ivey (1983) suggests that paracetamol is the analgesic/antipyretic of choice for adults or children with a history of upper gastrointestinal disturbances, portal hypertension and oesophageal varices, reflux oesophagitis, or a bleeding tendency (see also Ivey, this issue).…”

Section: Gastrointestinal Effectsmentioning

confidence: 99%

Paracetamol and Phenacetin

Clissold¹

1986

Drugs

214

107

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Since their synthesis in the late l800s paracetamol (acetaminophen) and phenacetin have followed divergent pathways with regard to their popularity as mild analgesic/antipyretic drugs. Initially, paracetamol was discarded in favour of phenacetin because the latter drug was supposedly less toxic. Today the opposite is true. and paracetamol. along with aspirin. has become one of the two most popular 'over-the-counter' non-narcotic analgesic agents. This marked increase in the wide approval attained by paracetamol has been accompanied by the virtual commercial demise of phenacetin because of its role, albeit somewhat circumstantial. in causing analgesic nephropathy.Both paracetamol and phenacetin are effective mild analgesics, suitable for treating mild to moderate pain. and their actions are broadly comparable with those of aspirin and related salicylates. although they do not appear to possess significant anti-inflammatory activity. Since a major portion of a dose of phenacetin is rapidly metabolised to paracetamol. it seems possible that phenacetin owes some of its therapeutic activity to its main metabolite. paracetamol. whereas its most troublesome side effect (methaemoglobinaemia) is due to another metabolite. p-phenetidine. The mechanism of action of paracetamol is poorly defined. although it has been speculated that it may selectively inhibit prostaglandin production in the central nervous system. which would account for its analgesic/antipyretic properties. The lack of any significant influence on peripheral cyclooxygenase would explain the absence of anti-inflammatory activity.At therapeutic doses paracetamol is well tolerated and produces fewer side effects than aspirin. The most frequently reported adverse effect associated with paracetamol is hepatotoxicity. which occurs after acute overdosage (usually doses greater than 10 to 15g are needed) and. very rarely. during long term treatment with doses at the higher levels of the therapeutic range. Paracetamol damages the liver through the formation of a highly reactive metabolite which is normally inactivated by conjugation with glutathione. Overdoses of par aceta mol exhaust glutathione stores. thus allowing the accumulation of this toxic metabolite which covalently binds with vital cell elements and can result in liver necrosis. Glutathione precursors (notably intravenous N-acetylcysteine) have proved remarkably successful in treating paracetamol overdose, as long as treatment is initiated within 10 hours.Apart from pharmacokinetic drug interactions resulting from changes in gastric emptying rate. there have been very few reports of clinically important drug-drug interactions involving paracetamol or phenacetin.The pre-eminent position of paracetamol and aspirin as the non-narcotic analgesic agents of choice for mild to moderate pain is being seriously challenged by 'newer' nonsteroidal anti-inflammatory drugs. Some of these newer agents have been found to have significantly superior analgesic activity and. in some cases. longer durations of action.

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Section: Gastrointestinal Effectsmentioning

confidence: 99%

Paracetamol and Phenacetin

Clissold¹

1986

Drugs

214

107

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“…Furthermore, acetylsalicylic acid was reported to reduce gastric mucosal ATP and to uncouple and/or inhibit mitochondrial oxidative phosphorylation. 21,22 The decrease in the ATP and TAN levels in the present study may reflect this action. The TAN are considered to be a potential energy source for tissues.…”

Section: Discussionmentioning

confidence: 58%

“…Furthermore, gastric mucosal injury may be caused by impaired ATPdependent bicarbonate ion transport due to decreased ATP. 21 In the NSAID group, decreases in the ATP level and no significant differences in the AMP level were observed in both the antrum and corpus. These findings indicate the depletion of ATP in the entire stomach (i.e.…”

Section: Discussionmentioning

confidence: 84%

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Role of energy metabolism in drug‐induced acute gastric mucosal injuries in humans

Sasahara

Uchida

Matsuda

et al. 2000

J of Gastro and Hepatol

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“…Score 0 = keine Veränderungen Score 1 = Erythem Score 2 = 10 Läsionen (Petechien/Erosionen) Score 3 = 10 Läsionen Score 4 =Ulkus Die zum Teil ausgeprägten gastroduodenalen Nebenwirkungen nicht-steroidaler Antirheumatika stellen mehr und mehr ein schwerwiegendes, klinisch relevantes Problem dar. Die enge Beziehung zwischen gastrointestinalen Schleimhautläsionen und einer Therapie mit NSAR ist heute durch zahlreiche epidemiologische Untersuchungen an großen Patientenkollektiven eindeutig belegt (1,5,7,11,18,20). Die Dauertherapie mit diesen Medikamenten führt zu einer Steigerung der Inzidenz des peptischen Ulkus um das 3-bis 5fache.…”

Section: The Gastrolesive Potency Oftenoxicam and Diclofenac-a Doubleunclassified