Drug-disease interactions: narrative review of aspirin in gastric ulcer

ABSTRACT

Introduction: Drug-disease interactions include the impact of a drug and a particular disease condition on each other. However, the current practice in addressing drug-disease interaction is unbalanced and mostly limited to how the drug worsens the disease or health condition.

Areas covered: Aspirin and gastric ulcer interaction are used as an example to illustrate this concept, especially the narration of how disease affects drug efficacy. The number of molecules that make up 100 mg of aspirin is identified with a view to discuss the pharmacokinetics, especially in terms of absorption and distribution. Using hypothetical scenarios, the pharmacodynamics in co-morbidities that could involve gastric ulcer and aspirin are also discussed.

Expert opinion: There seems to be oversight in definition and description of drug-disease interaction, which is often limited to ‘how drug exacerbates disease’. The implication of this limited definition is that the discussions, research and teaching of the topic either lacks information, or are not clear on ‘how disease affects drug efficacy’. For example, gastric ulcer has the potential to enhance absorption, bioavailability and therapeutic effects of aspirin, but this is rarely discussed in preference to the probability of gastro-intestinal bleeding side-effect.

KEYWORDS:

• Anti-inflammatory drugs
• antiplatelet function
• co-morbidities
• drug-disease interactions
• gastric ulcer
• pharmacodynamics and pharmacokinetics

Article highlights

• There seems to be common oversight in definition and description of drug-disease interaction, which is often limited to ‘how drug exacerbates disease’. The implication of this limited definition is that the discussions, research and teaching of the topic is often lacking in information on ‘how disease affects drug efficacy’.

• Antiplatelet efficacy may be dependent on degree of inflammation, which is negative ‘effect of disease on drug’ in the drug-disease interaction

• While GU-induced inflammation could reduce the antiplatelet efficacy of aspirin, GU effect on pH enhances absorption, which could be positive effect of disease on drug in the drug-disease interaction, but this is rarely discussed in preference to the probability of gastro-intestinal bleeding side-effect.

• Arguably, the negative side-effect of exacerbated GI bleeding is deemed to outweigh the positive side-effect of enhanced absorption and bioavailability. The positive effects have yet to be investigated. It would be interesting to determine whether (a) increase in bioavailability is proportional to level of GI bleeding, (b) efficacy of the drug on co-morbid conditions is proportionally improved, or (c) there is GI bleeding level – drug dosage – bioavailability level that is optimal

• Assuming the aspirin has been prescribed for GU only, it can be argued that the amount of the drugs distributed beyond the GI to cause these positive side-effects on diabetes-induced inflammation and/or anti-thrombogenesis constitute a fraction of the dosage unavailable at GIT to cause bleeding. On the other hand, if the aspirin has been prescribed for diabetes and its complications, the fraction of the drug that causes GI bleeding/damage in the GIT tissues is actually unavailable to alleviate inflammation or stasis in the coronary or peripheral blood vessels. In either case, co-morbidity is affecting the drug pharmacodynamics in the context of drug-disease interactions.

This box summarizes key points contained in the article.

Acknowledgments

Kay Skinner and Phillip Bwititi have independently edited the revised manuscript for grammar corrections. The authors are grateful for their kind support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.