The "Forgotten Side Effect" of Thiazides

Problem statement: Thiazide diuretics are derived from benzodiazines. They inhibit Na⁺/Cl^- re-absorption from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na⁺/Cl^- symporter. They are recommended as first line treatment for hypertension in the US (JNC VII)^[1] guidelines and in the National Institute of Health and Clinical Excellence/British Hypertension Society guidelines^[2] and in the European (ESC/ESH)^[3] guidelines. They have been shown to prevent hypertension-related morbidity and mortality, although the long term mechanism is not fully understood. Approach: Side effects include hypokalemia, increased serum cholesterol, impaired glucose intolerance, diabetes mellitus and impotence. Long term usage of thiazides is also linked to increased levels of homocysteine and a paradoxical effect in Diabetes Insipidus, where they reduce urine volume. However, there is a side effect that was ignored during the last 30 years-and that is the association with gall bladder disease. We would like to stress this side effect. Results: Thiazide diuretics have a “forgotten” side effect that was not mentioned among the well-known side effects of the drug. Conclusion: The mechanism is not completely understood, but the association is clear and physicians should be aware of that side effect.