Coxibs Refocus Attention on the Cardiovascular Risks of Non-Aspirin NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) were differentiated from steroidal anti-inflammatory medicines to help clinicians who needed to use anti-inflammatory agents that were safer than steroids. With market entry of rofecoxib in 1999, NSAIDs were then further classified into traditional NSAIDs and cyclooxygenase (COX)-2 inhibitors (coxibs), the latter posing potentially fewer gastrointestinal risks. In 2005, rofecoxib was withdrawn from the market because of concerns about the risk of heart attack and stroke with long-term use, and clinical practice began focusing more on the cardiovascular versus gastrointestinal safety of coxibs. Since then, many coxibs have remained unapproved by the US FDA or have been removed from the market. This article explains how coxibs refocused attention on the cardiovascular safety of NSAIDs and the general implications of that. COX-2 activity/specificity is one factor associated with increased cardiovascular risks; however, these risks cannot be attributed to coxibs alone. The traditional NSAIDs (i.e., meloxicam, etodolac, and nabumetone) have significant COX-2 specificity, but naproxen and ibuprofen have less specificity. All NSAIDs, whether traditional or a coxib, pose some cardiovascular risks. It is possible that clinicians continue to focus more on decreasing the immediate gastric risks than preventing the later cardiovascular risks. The cardiovascular risks posed by NSAIDs should not be disregarded for the sake of achieving gastrointestinal benefits. Current recommendations suggest NSAIDs should be considered a single class of non-aspirin NSAIDs. Preferred NSAIDs are ibuprofen and naproxen. Coxibs are preferred in patients with low cardiovascular risk and high gastrointestinal risk who are intolerant to anti-dyspepsia therapy.

Therapeutic failure of primaquine and need for new medicines in radical cure of Plasmodium vivax.

Primaquine has been the drug of choice for the prevention of Plasmodium vivax relapse for more than 60 years. Primaquine tolerant strain of P. vivax was identified in 1944. Significant mortality and disease burden of P. vivax calls for the need of new drugs. Primaquine resistance is a complex issue, as the mechanism of resistance is not clear. Direct evidence of resistance to primaquine by hypnozoites has not yet been shown. There are some reports detailing risk of primaquine resistance in specific regions, but the overall distribution of primaquine resistance in P. vivax-infected people is largely unknown. Confounding factors contribute to treatment failures; such as inadequate doses, inappropriate dosing intervals, risk of reinfection, combinations with blood schizontocidals, and compliance. Therefore, primaquine resistance needs to be addressed along with additional important confounding factors. Tafenoquine is the most studied drug in replacing primaquine for the radical cure of P. vivax malaria. It has comparable efficacy with primaquine. The potential advantage of tafenoquine is better compliance with a single dose regimen. Rational use of primaquine can secure its effectiveness, but it is essential in the future to have better or similar alternatives to treat P. vivax.