Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study.

AIM: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population. METHODS: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time. RESULTS: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs. CONCLUSION: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

Intrathecal therapy with ziconotide: clinical experience and considerations on its use.

Ziconotide is a synthetic peptide equivalent of an w-conotoxin, obtained from the marine snail Conus magus, which acts by blocking N-type calcium channels in the spinal cord, reducing the perception of pain. It is a newly marketed drug, exclusively for intrathecal use, indicated for severe chronic pain. Ziconotide came to the physicians' table with both doubts and promises; to determine its safety and efficacy, one of the largest and most well-designed randomized double-blind studies in the history of intrathecal therapy was undertaken, and this drug demonstrated efficacy in relieving chronic pain in patients coming from many years of different therapies and therapy failures. However, the pain relief came with some adverse effects, which are few compared with morphine's adverse effects but in some cases could undermine the course of therapy with this conotoxin. The experience described in this paper began in June 2007 and gave us the opportunity to analyze how the conotoxin works outside of the papers. We noted differences between the well-known activity of morphine on pain and mood, and the more focused action of ziconotide on pain. In addition, it is important to consider the lack of addiction, opioid-induced hyperalgesia and other systemic effects that are common with morphine. These are the reasons why the Polyanalgesic Consensus Conference of 2007 put ziconotide in the first line of intrathecal therapy management.