Inhibitors of steroidal cytochrome p450 enzymes as targets for drug development

November 2017 - Dr Hayley Willacy has been reading recent reports concerning long-term use of PPI medicines and an increased risk of gastric (stomach) cancer - see Further reading below. Researchers from Hong Kong studied 63,397 people who'd been treated for stomach infection with H. pylori bacteria. Even after the bacteria had been killed, those who took PPIs on a long-term basis were more likely to be diagnosed with stomach cancer in the following 7 to 8 years of follow-up. Because of the study design, we can't tell if PPIs were the cause of the increased stomach cancer risk. It could also have been down to other factors. For instance, the people studied were Chinese and we now that Asian people already have a higher risk of stomach cancer than the general European or US population. The amount of alcohol or how much these people smoked are also key factors and unfortunately, this was not looked at in the study. It is also important to keep the results in proportion. Long-term use of PPIs was linked to around 4 additional stomach cancers cases per 10,000 people per year. The overall risk is still very low.

It may be that the greatest risk of inducing a myocardial infarction is in a patient with undiagnosed coronary vascular disease. Before COX-2 selective inhibitors became available, this patient may have been prescribed another NSAID. This would have had an aspirin-like antiplatelet effect and, if anything, might have been expected to reduce the risk of infarction. If the patient is instead commenced on a COX-2 selective inhibitor the balance swings towards a prothrombotic state that theoretically might result in an infarction. This theoretical point is supported by the results of the VIGOR study and the termination of the APPROVe study because of an excess risk of myocardial infarction and stroke in patients taking rofecoxib for 18 months.

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  • Citation tools Download this article to citation manager Shin Ju-Young , Park Mi-Ju , Lee Shin Haeng , Choi So-Hyun , Kim Mi-Hee , Choi Nam-Kyong et al. Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study BMJ 2015; 351 :h3517
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    Inhibitors of steroidal cytochrome p450 enzymes as targets for drug development

    inhibitors of steroidal cytochrome p450 enzymes as targets for drug development

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  • Citation tools Download this article to citation manager Shin Ju-Young , Park Mi-Ju , Lee Shin Haeng , Choi So-Hyun , Kim Mi-Hee , Choi Nam-Kyong et al. Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study BMJ 2015; 351 :h3517
    • BibTeX (win & mac) Download
    • EndNote (tagged) Download
    • EndNote 8 (xml) Download
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    • RIS (win only) Download
    • Medlars Download
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