Hydrochlorothiazide is a

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

medication often used to treat

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

and swelling due to fluid build-up. Other uses include treating

diabetes insipidus Diabetes insipidus (DI), recently renamed to Arginine Vasopressin Deficiency (AVP-D) and Arginine Vasopressin Resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produce ...

and

renal tubular acidosis Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate pas ...

and to decrease the risk of

kidney stone Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

s in those with a high calcium level in the urine. Hydrochlorothiazide is less effective than

chlortalidone Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling including that due to heart failure, liver failure, and nephrotic syndrome, diabetes insipidus, and renal tubular aci ...

for prevention of

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. Hydrochlorothiazide is taken by mouth and may be combined with other

blood pressure medication Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that r ...

s as a single pill to increase effectiveness. Potential side effects include poor kidney function;

electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...

s, including

low blood potassium Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnor ...

, and, less commonly,

low blood sodium Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...

high blood sugar Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

, and

feeling lightheaded with standing Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

. While

allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

to hydrochlorothiazide 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 Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

medication class and acts by decreasing the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s' ability to retain water. This initially reduces

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

volume, decreasing blood return to the heart and thus

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...

. It is believed to lower peripheral

vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be ca ...

in the long run. Two companies,

Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...

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 WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. It is available as a

generic drug A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

and is relatively affordable. In 2020, it was the eleventh most commonly prescribed medication in the United States, with more than 41million prescriptions.

Medical uses

Hydrochlorothiazide is used for the treatment of

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, symptomatic

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

. It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine. Multiple studies suggest hydrochlorothiazide could be used as initial monotherapy in people with primary hypertension; however, the decision should be weighed against the consequence of long-term adverse metabolic abnormalities.The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA: The Journal of the American Medical Association. 2002;288(23):2981-2997. A review of randomised trials showed varying efficacy in cardiovascular outcomes on age, ethnicity and existing cardiovascular risks. A systematic, multinational, large-scale analysis by Suchard et al. supported equivalence between drug classes for initiating monotherapy in hypertension, however thiazide or thiazide-like diuretics showed better primary effectiveness and safety profiles than angiotensin-converting enzyme inhibitors and non-dihydropyridine calcium channel blockers. Hydrochlorothiazide is less potent but not necessarily less effective than chlorthalidone in reducing blood pressure.Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJG, Phillips BB, Zimmerman MB, et al. Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure. Hypertension. 2006;47(3):352-8.Peterzan MA, Hardy R, Chaturvedi N, Hughes AD. Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate. Hypertension. 2012 Jun;59(6):1104-9. More robust studies are required to confirm which drug is superior in reducing cardiovascular events.Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone Reduces Cardiovascular Events Compared With Hydrochlorothiazide: A Retrospective Cohort Analysis. Hypertension. 2011;57(4):689-94. Side effect profile for both drugs appear similar and are dose dependant. Hydrochlorothiazide is also sometimes used to prevent

osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteop ...

and for treatment of

hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...

hypercalciuria Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that put out higher levels ...

Dent's disease Dent's disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urin ...

, and

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initial ...

. 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. A low level of evidence, predominantly from observational studies, suggests that thiazide diuretics have a modest beneficial effect on bone mineral density and are associated with a decreased fracture risk when compared with people not taking thiazides. Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation. The combination of fixed-dose preparation such as losartan/hydrochlorothiazide has added advantages of a more potent antihypertensive effect with additional antihypertensive efficacy at the dose of 100 mg/25 mg when compared to monotherapy.

Adverse effects

Hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...

, or low blood levels of potassium are an occasional side effect. It can be usually prevented by

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...

supplements or by combining hydrochlorothiazide with a

potassium-sparing diuretic Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldostero ...

* Other disturbances in the levels of serum electrolytes, including

hypomagnesemia Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, an ...

(low magnesium),

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...

(low sodium), and hypercalcemia (high calcium) *

Hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...

(high levels of

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...

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 incidence of gout in doses of ≥ 25 mg per day and in more susceptible patients such as male gender of <60 years old. *

Hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

, high blood sugar *

Hyperlipidemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...

, high cholesterol and triglycerides *

Headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

Nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

Photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. ...

Weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs wh ...

Pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...

Package inserts contain vague and inconsistent data surrounding the use of thiazide diuretics in patients with allergies to sulfa drugs, with little evidence to support these statements. A retrospective cohort study conducted by Strom et al. concluded that there is an increased risk of an allergic reaction occurring in patients with a predisposition to allergic reactions in general rather than cross reactivity from structural components of the sulfonamide-based drug. Prescribers should examine the evidence carefully and assess each patient individually, paying particular attention to their prior history of sulfonamide hypersensitivity rather than relying on drug monograph information. There is an increased risk of non-melanoma skin cancer. In August 2020, the Australian

Therapeutic Goods Administration The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health and Aged Care, the TGA regulates the quality, supply and advertising of medicines, pa ...

required the Product Information (PI) and Consumer Medicine Information (CMI) for medicines containing hydrochlorothiazide to be updated to include details about an increased risk of non-melanoma skin cancer. In August 2020, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) updated the drug label about an increased risk of non-melanoma skin cancer (basal cell skin cancer or squamous cell skin cancer).

Mechanism of action

Hydrochlorothiazide belongs to the

class of

s. It reduces blood volume by acting on the

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

to reduce

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...

(Na⁺) reabsorption in the

distal convoluted tubule The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...

. 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 Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldosterone. Natriuresis lowers t ...

and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport. Additionally, by other mechanisms, hydrochlorothiazide is believed to lower peripheral vascular resistance.

Dosage

In a double-blind, randomized study, the effects of 25 mg/day vs. 50 mg/day of hydrochlorothiazide were evaluated in geriatric patients (n = 51) with isolated systolic hypertension. Both dosages were associated with similar reductions in blood pressure; however, the higher dose (50 mg/day) caused a greater decline in serum potassium concentration.

Society and culture

Brand names

Hydrochlorothiazide is available as a

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 Polypharmacy (polypragmasia) is the simultaneous use of multiple medicines by a patient for their conditions. Most commonly it is defined as regularly taking five or more medicines but definitions vary in where they draw the line for the minimum ...

and in order to reduce side effects, hydrochlorothiazide is often used in

fixed-dose combinations A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

with many other classes of antihypertensive drugs such as: *

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

s — e.g. Prinzide or Zestoretic ( with lisinopril), Co-Renitec (with

enalapril Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furose ...

), Capozide (with

captopril Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...

), Accuretic (with quinapril), Monopril HCT (with

fosinopril Fosinopril is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphonate-containing ACE inhibitor marketed, by Bristol-Myers Squibb under t ...

), Lotensin HCT (with

benazepril Benazepril, sold under the brand name Lotensin among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Ver ...

), etc. *

Angiotensin receptor blocker Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

s — e.g. Hyzaar ( with losartan), Co-Diovan or Diovan HCT ( with valsartan), Teveten Plus (with

eprosartan Eprosartan is an angiotensin II receptor antagonist used for the treatment of high blood pressure. It is marketed in the United States as ''Teveten'' by Abbvie, the spin-off of the pharmaceutical discovery division of Abbott Laboratories; it i ...

), Avalide or CoAprovel (with

irbesartan Irbesartan, sold under the brand name Avapro among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versi ...

), Atacand HCT or Atacand Plus (with

candesartan Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. The metabolism for the drug is unique as it is a cascading prodrug. Ca ...

), etc. *

Beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...

s — e.g. Ziac or Lodoz (with

bisoprolol Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is ...

), Nebilet Plus or Nebilet HCT (with

nebivolol Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. I ...

), Dutoprol or Lopressor HCT (with

metoprolol Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...

), etc. * Direct renin inhibitors — e.g. Co-Rasilez or Tekturna HCT (with

aliskiren Aliskiren (brand names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically rec ...

) * Potassium sparing diuretics: Dyazide and Maxzide

triamterene Triamterene (trade name Dyrenium among others) is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is known as hydro ...

Sport

Use of hydrochlorothiazide is prohibited by the

World Anti-Doping Agency The World Anti-Doping Agency (WADA; french: Agence mondiale antidopage, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The agency's key ...

for its ability to mask the use of performance-enhancing drugs.

References

External links

* {{Portal bar, Medicine AMPA receptor positive allosteric modulators Antihypertensive agents Benzothiadiazines Merck brands Carbonic anhydrase inhibitors Diuretics IARC Group 2B carcinogens Sulfonamides Thiazides World Anti-Doping Agency prohibited substances World Health Organization essential medicines Wikipedia medicine articles ready to translate Sultams