|Trade names||Apo-hydro, others|
|By mouth (capsules, tablets, oral solution)|
|Bioavailability||Variable (~70% on average)|
|Elimination half-life||5.6–14.8 h|
|Excretion||Primarily kidney (>95% as unchanged drug)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||297.74 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Hydrochlorothiazide (HCTZ or HCT) 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, although chlortalidone is more effective with a similar rate of adverse effects. 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, which lists the most effective and safe medicines needed in a health system. It is available as a generic drug and is relatively affordable. In 2016, it was the 12th most prescribed medication in the United States, with more than 43 million prescriptions.
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.
Most of the research supporting the use of thiazide diuretics in hypertension was done using chlortalidone, a different medication in the same class. Hydrochlorothiazide is less effective than chlortalidone for lowering blood pressure but the two medications have similar effects on lowering potassium. The thiazide-type diuretics (including hydrochlorothiazide) are less effective than the thiazide-like diuretics (chlortalidone and indapamide) for reducing the risk of heart attack, stroke, and heart failure in persons with high blood pressure and the thiazide-like and thiazide-type diuretics have similar rates of adverse 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 (see below).
- Hypokalemia, or low blood levels of potassium are an occasional side effect. It can be usually prevented by potassium supplements or by combining hydrochlorothiazide with a potassium-sparing diuretic
- Other disturbances in the levels of serum electrolytes including hypomagnesemia (low magnesium), hyponatremia (low sodium), and hypercalcemia (high calcium)
- Hyperuricemia (high levels of uric acid in the blood). All thiazide diuretics including hydrochlorothiazide can inhibit excretion of uric acid by the kidneys, thereby increasing serum concentrations of uric acid. This may increase the chance of gout.
- Hyperglycemia, high blood sugar
- Hyperlipidemia, high cholesterol and triglycerides
- Weight gain
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 (Na+) 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
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.
- ACE inhibitors — e.g. Prinzide or Zestoretic (with lisinopril), Co-Renitec (with enalapril), Capozide (with captopril), Accuretic (with quinapril), Monopril HCT (with fosinopril), Lotensin HCT (with benazepril), etc.
- Angiotensin receptor blockers — e.g. Hyzaar (with losartan), Co-Diovan or Diovan HCT (with valsartan), Teveten Plus (with eprosartan), Avalide or CoAprovel (with irbesartan), Atacand HCT or Atacand Plus (with candesartan), etc.
- Beta blockers — e.g. Ziac or Lodoz (with bisoprolol), Nebilet Plus or Nebilet HCT (with nebivolol), Dutoprol or Lopressor HCT (with metoprolol), etc.
- Direct renin inhibitors — e.g. Co-Rasilez or Tekturna HCT (with aliskiren)
- Potassium sparing diuretics: Dyazide and Maxzide triamterene
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