PubMed · 15658345
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Mikio Yashiki, Akira Namera, Manami Nishida. 2004. [Acetaminophen].. https://pubmed.ncbi.nlm.nih.gov/15658345/
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BACKGROUND: In the absence of objective symptoms, it is difficult to assess an adverse reaction during drug provocation testing. We evaluated the value of serum tryptase levels to distinguish between positive, negative and, even more important, so-called 'hysterical' reactions (conversion symptoms). The latter are occasionally observed in drug provocation tests when the patient experiences ambiguous subjective symptoms. METHODS: In a prospective single-center study, 303 patients underwent 785 drug provocation tests. Blood was taken for tryptase measurement on each test day before and after drug challenge, and the changes in serum tryptase levels in patients with no reactions were compared with those who experienced immediate reactions to a drug. RESULTS: Thirty-four of 785 drug provocations were clinically judged as being positive. Despite objective symptoms, median serum tryptase values in the afternoon were even lower than baseline levels. However, this decrease was not statistically significant. In the 751 patients suffering no objective reactions, the median values of post-testing tryptase values were statistically significantly decreased as compared with pretesting values. CONCLUSIONS: The measurement of serum tryptase levels does not appear to be helpful to differentiate mild allergic or nonallergic reactions from 'hysterical' ones. The milder decrease in the group with objective drug reactions might indicate slight mast cell activation in some patients. More severe clinical drug reactions led to stronger mast cell degranulation. Mild reactions did not increase the tryptase levels consistently.
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The fixed combination of aspirin, paracetamol (acetaminophen) and caffeine has been used successfully to treat different kinds of pain including migraine attacks. Even when this formulation has been marketed for a long time, the exact molecular mechanisms underlying its therapeutic effectiveness have not been completely elucidated. In the present investigation, we have studied the effects of the fixed combination of aspirin, paracetamol and caffeine (APC) on the release of dopamine and noradrenaline from rat striatal slices in an attempt to find potential new mechanisms of action of this widely used analgesic combination. We found that APC produced a significant reduction in extracellular dopamine and a dramatic increase in norepinephrine release from the slices incubated with different concentrations of APC (dose relationship 1:1:0.2, corresponding to the dose-relationship of Thomapyrin). These findings suggest that the modulation of catecholaminergic neurotransmission is a new pharmacological effect of APC which could explain the mechanism of action of this formulation, considering that the independent effect of either compound alone does not explain the potent antinociceptive properties when observed in combination.