CONTROVERSY Should we give up hydrochlorothiazide as the diuretic of choice in hypertension? Agonist ALFREDO O. WASSERMANN 1 The answer to this question could be considered as too normative, but a comparison between hydrochlorothiazide (HCTZ) and other diuretics available –particularly chlorthalidone (CT) and indapamide– would let us approach what would be the best choice of a diuretic for a scheme of antihypertensive treatment. Thiazide-related drugs are among the most commonly drugs used to treat hypertension; antihypertensive action and benefits to risk reduction for several final indicators have been widely documented (1) and should be included in all the schemes prior to considering refractory a patient who does not meet the therapeutic goals. Although there are several drugs in the group, the most commonly used –and almost exclusively in our environment– in clinical trials are HCTZ and CT; more recently, IP was introduced, and although it is classified as akin to this group, some of its characteristics are different. PHARMACOLOGICAL PROPERTIES OF THE FAMILY OF THIAZIDES HCTZ and CT share the site and the mechanism of action, while IP would have additional effects on vessels and on other segments of the renal tubule. Introduction to the controversy RAC Editing Committee 1 Nephrologist at the Hospital Municipal de Vicente López Medical Director of FEPREVA: Fundación para el Estudio, la Prevención y el Tratamiento de la Enfermedad Vascular Aterosclerótica (Foundation for the Study, Prevention and Treatment of Atherosclerotic Vascular Disease) Consensus on hypertension propose thiazides as the first order drugs for its treatment. In practice, hydrochlorothiazide is the most common thiazide for antihypertension, 97% of the prescriptions include diuretics as individual or combined agents. In recent years, the detailed analysis of the published information showed that the greatest benefits from thiazides in clinical trials had been achieved with chlorthalidone and indapamide, whereas there were fewer evidences of the clinical benefit and potency of hydrochlorothiazide in usual doses. These revisions have raised the debate about the need to replace hydrochlorothiazide, with preference to other agents. In the last European Congress of Cardiology, Frank Messerli –as agonist– and Susane Oparyl –as defender of hydrochlorothiazide– participated in this controversy. The RAC (Argentine Journal of Cardiology) Editing Committee tried to bring this controversy to the local level, but it could not be settled. The reason was unexpected: Despite having asked a high number of specialists in hypertension, we were unable to find someone to defend the hydrochlorothiazide. Still, we have decided to publish the agonist’s arguments, with the intention of leaving open the possibility for readers to send a refutation to his arguments. It still causes concern that the diuretic of choice in practice is indefensible in theory. HCTZ has a half life of 2.5 ± 0.2 hours, which gives a duration of action of 18 hours, while CT has a half life of 47 ± 22 hours and a duration of action over 72 hours; these figures vary in the literature. (2, 3) In patients with normal renal function, duration of action of HCTZ is approximately 18 hours and, as with other diuretics whose duration of action is < 24 hours and are administered in once-daily dosing, Na+ could be retained during the period with no pharmacological action. (4) In addition, the potency of CT is 1.5 to 2 times greater; this could be related in part to the increased volume of distribution based on its high concentration of red blood cells. (5) These pharmacokinetic properties will determine the greater potency through an accummulation of the drug, usually administered at intervals shorter than its half life; therefore, effects are more evident when compared to repeated doses with cumulative effect until the administration-elimination balance is reached, usually with the fifth dose. The effect of both drugs would be similar with single doses. The longer duration of action is relevant in the treatment of hypertension, since the desired drugs are those which maintain their therapeutic effectiveness with a once- daily dosing, and so is the protection conferred to BP maintainence in case of missing a dose. Greatest potency should be considered when comparing both the therapeutic and adverse effects,