“Triple Whammy” effect

You may have seen the term “triple whammy” referred to in recent literature. The term describes a phenomenon in which a combination of frequently used medications, Ace- Inhibitors (ACE-I) or Angiotensin Receptor Blockers (ARB), non-steroidal anti-inflammatory agents (NSAIDs, including aspirin) and/or diuretics, results in impaired renal function.

Most of the patients attending general practices in our country were on a such a combination of medications, potentially leading to renal dysfunction. Two mechanisms are thought to primarily be involved in the pathogenesis of renal dysfunction and the “triple whammy” effect. Drugs that impact the renin-angiotensin system, as well as NSAIDs, decrease afferent arteriolar vasodilation. Diuretics decrease plasma volume. Synergistically, these mechanisms can lead to decreased renal blood flow and subsequent renal dysfunction.
The elderly are thought to be more susceptible to the “triple whammy” effect due to a decreasing glomerular filtration rate, as well as decreased compensatory abilities. Age and pre-existing renal impairment are the most likely factors to increase the risk of developing such adverse effects. Treatment considerations for this population may include the use of acetaminophen or opioids over NSAID for pain relief, low doses and slow titration of loop agents when diuresis is necessary, and cautious use of potassiumsparing diuretics in patients already receiving angiotensin agents in combination with NSAIDs.