Hydrochlorothiazide


Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up. Other uses include diabetes insipidus, renal tubular acidosis, and to decrease the risk of kidney stones in those with a high calcium level in the urine. For high blood pressure it is sometimes considered as a first-line treatment. HCTZ is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness.
Potential side effects include poor kidney function, electrolyte imbalances including low blood potassium and less commonly low blood sodium, gout, high blood sugar, and feeling lightheaded with standing. While allergies to HCTZ are reported to occur more often in those with allergies to sulfa drugs, this association is not well supported. It may be used during pregnancy, but it is not a first-line medication in this group.
It is in the thiazide medication class and acts by decreasing the kidneys' ability to retain water. This initially reduces blood volume, decreasing blood return to the heart and thus cardiac output. It is believed to lower peripheral vascular resistance in the long run.
Two companies, Merck and Ciba, state they discovered the medication which became commercially available in 1959. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic drug and is relatively affordable. In 2017, it was the twelfth most commonly prescribed medication in the United States, with more than 42 million prescriptions.

Medical uses

Hydrochlorothiazide is frequently used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis. It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine.
A 2019 review found that it was less effective than chlortalidone but also had fewer side effects.
Hydrochlorothiazide is also sometimes used to prevent osteopenia and for treatment of hypoparathyroidism, hypercalciuria, Dent's disease, and Ménière's disease. For diabetes insipidus, the effect of thiazide diuretics is presumably mediated by a hypovolemia-induced increase in proximal sodium and water reabsorption, thereby diminishing water delivery to the ADH-sensitive sites in the collecting tubules and increasing the urine osmolality.
Thiazides are also used in the treatment of osteoporosis. Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.
It may be given together with other antihypertensive agents in fixed-dose combination preparations, such as in losartan/hydrochlorothiazide.

Adverse effects

The frequency of side effects increase as the medication dose is increased and the highest occurrence of side effects occur at doses greater than 25 mg per day.
Package inserts, based on case reports and observational studies, have reported that an allergy to a sulfa drug predisposes the patient to cross sensitivity to a thiazide diuretic. A 2005 review of the literature did not find support for this cross-sensitivity.

Mechanism of action

Hydrochlorothiazide belongs to thiazide class of diuretics. It reduces blood volume by acting on the kidneys to reduce sodium reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral NaCl co-transporter by competing for the chloride site on the transporter. By impairing Na+ transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport. Additionally, by other mechanisms, HCTZ is believed to lower peripheral vascular resistance.

Society and culture

Trade names

Hydrochlorothiazide is available as a generic drug under a large number of brand names, including Apo-Hydro, Aquazide, BPZide, Dichlotride, Esidrex, Hydrochlorot, Hydrodiuril, HydroSaluric, Hypothiazid, Microzide, Oretic and many others.
To reduce pill burden and in order to reduce side effects, hydrochlorothiazide is often used in fixed-dose combinations with many other classes of antihypertensive drugs such as:
Use of hydrochlorothiazide is prohibited by the World Anti-Doping Agency for its ability to mask the use of performance-enhancing drugs.