Med anledning av ett reklamtryck frågas om följande påståenden är dokumenterade: 1) Salicylsyra häm

Fråga: Med anledning av ett reklamtryck frågas om följande påståenden är dokumenterade: 1) Salicylsyra hämmar till skillnad från ASA ej magslemhinnans cyklooxygenas i djurförsök. 2) ASA ger kraftigare blodförlust än salicylsyra vid tillförsel i kontrollerade försök. 3) ASA ger en irreversibel hämning av trombocytaggregation medan tillförsel av salicylat ej ger sådan hämning. 4) Salicylat skulle däremot kunna ha en selektiv cyklooxygenashämning i inflammerad vävnad.

Sammanfattning: There is no reason to believe that sodium salicylate will be less toxic to the gastric mucosa than aspirin. There are major differences in the sensitivity to drugs of cyclooxygenases in different tissues and species, and animal data cannot be applied to man. The separateness of salicylate induced GI distress, microbleeding, and gastric ulceration should be understood.

Svar: While the few points made in this advertisement (1) are supported by the articles cited, their clinical relevance is doubtful. These points made, and their references, are as follows (additional information not in the advertisement is given in parentheses).

a) Aspirin (as well as indomethacin, naproxen and ibuprofen) inhibits rat gastric-mucosal cyclooxygenase activity, but sodium salicylate does not (2).

b) Aspirin causes more (minor) gastrointestinal blood loss than sodium salicylate (3). (After 12x325 mg daily doses, blood loss was 6.3 ml with aspirin, 1.9 ml with sodium salicylate and 0.9 ml for controls).

c) Aspirin irreversibly inhibits platelet cyclooxygenase, and consequently reduces platelet aggregation, while sodium salicylate is without effect on platelets (4).

d) Cyclooxygenase may be more sensitive to salicylate at the site of inflammation than at the gastric mucosa (2). (This study showed that, in the rat, salicylate, but not aspirin, selectively inhibited PGE2 formation produced by carrageenin inflammation without reducing PGI2 formation in the gastric mucosa).

These points are used to support the claim that sodium salicylate is less damaging to the gastric mucosa than aspirin. Unfortunately the key experiments (2) were performed in the rat (there are marked species differences in GI effects of salicylates (5)) and no clinical evidence was presented. Furthermore, in this rat study there was no simple relationship between inhibition of PGI2 formation and gastric erosion amongst the 6 drugs tested (2).

The major difficulty with this advertisement comes from its confusion about three separate gastrointestinal (GI) effects of aspirin and salicylate: symptomatic GI distress, microbleeding and gastritis-ulceration (5).

The first set of symptoms ranging from mild to severe discomfort, seem to involve at least partly, a central nervous system effect since they can be elicited after intravenous sodium salicylate. There also seems to be a placebo component to the GI distress symptoms (5).

Microbleeding and gastroscopic changes are probably related to each other, but do not seem to be related to either major blood loss or GI distress (5). Aspirin, and to a lesser extent other nonsteroidal antiinflammatory agents, cause a slight increase in faecal blood loss, measured with 51Cr-labelled red cells. However, most patients with rheumatoid arthritis who take aspirin do not have occult blood loss, nor do they develop anaemia. The changes seen by endoscopy in the gastric mucosa, from hyperaemia to submucosed haemorrhage, superficial erosion and frank ulceration, have not be found to be associated with either GI distress or major GI bleeding. These changes can be prevented by adequate buffering, and are rapidly reversible.

Plotz (5) asserts that "there is no evidence whatsoever that the incidence of ulcer or major GI bleeding is any different with any other nonsteroidal antiinflammatory drug from what it is with aspirin". He also estimates that the risk of gastric ulceration and major GI bleeding from aspirin is low (25 per 100000 patients per year).

Finally, the particularly potent effect of aspirin on platelet cyclooxygenase does not seem to be related to gastric micro bleeding, since parenteral aspirin affects platelets but not the gastric mucosa (5). Furthermore, a patient who lacked platelet cyclooxygenase activity was apparently without illness (5). 1 Annons: Bidocyl - den återuppväckta salicylsyran. Observanda Medica Ferrosan 1983; 10: 130-133 2 Whittle BJR, Higgs GA, Eakins KE, Moncada S, Vane JR: Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa. Nature 1980; 284: 271-273 3 Leonard JR, Levy G: Gastrointestinal blood loss from aspirin and sodium salicylate tablets in man. Clin Pharmacol Ther 1973; 14: 62-66 4 Ross-Lee LM, Elms MJ, Cham BE, Bochner F, Bunce IH, Eadie MJ: Plasma levels of aspirin following effervescent and enteric coated tablets, and their effect on platelet function. Eur J Clin Pharmacol 1982; 23: 545-551 5 Plots PH: Aspirin and salicylate. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB: Textbook of Rheumatology, WB Saunders, 1981, pp 740-767