Month: February 2022

Thiazide diuretics and hypercalcaemia

Why is it said that thiazide diuretics may unmask hypercalcemia?

Thiazide diuretics increase the risk of hypercalcaemia. There are several mechanisms by which they have been reported to contribute to increased serum calcium levels, but most important is that they increase renal tubular reabsorption of calcium resulting in reduced calcium excretion in urine. Normally, this is not a problem for otherwise healthy individuals. However, thiazide diuretics are contraindicated in patients at risk of hypercalcaemia, for example, because of primary hyperparathyroidism or sarcoidosis.

Primary hyperparathyroidism is the most common cause of hypercalcaemia. Excessive secretion of parathyroid hormone (PTH), a key factor in calcium metabolism, results in the leaching of calcium from bone and increased production of calcitriol, the active form of Vitamin D, which increases intestinal absorption of calcium and reabsorption in the kidneys. Sarcoidosis is clinically observed to be associated with increased risk of hypercalcaemia, which is most frequently explained by overproduction of calcitriol by activated macrophages.

PPIs and C. difficile infection

Does the use of proton-pump inhibitors (PPIs) increase the risk of Clostridioides difficile infection?

Medical literature has debated whether PPIs increase the risk of C. difficile enteric infections for many years. Analysis of the issue has been complicated because proton-pump inhibitors are often taken together with antibiotics in triple therapy to eradicate Helicobacter pylori. Antibiotics can alter the normal gut microbiota allowing the proliferation of C. difficile. 

While the pathophysiological mechanisms remain unknown, the evidence increasingly supports the conclusion that PPIs increase the risk of C. difficile infection even without antibiotic use (Wolfe et al., 2021). There is a greater risk of C. difficile infection with PPIs than H2 receptor blockers (Kwok et al., 2012; Leonard et al., 2007). Although there is considerable variation among studies, overall PPIs also increase the risk of recurrent C. difficile infection (Kwok et al., 2012; Tariq et al., 2017).
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