American Journal of Pharmacology and Toxicology

The "Forgotten Side Effect" of Thiazides

Arnon Blum

DOI : 10.3844/ajptsp.2009.174.176

American Journal of Pharmacology and Toxicology

Volume 4, Issue 4

Pages 174-176


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.


© 2009 Arnon Blum. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.