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 first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available. Thiazide organic molecules are bi-cyclic structures that contain adjacent sulfur and nitrogen atoms on one ring. Confusion sometimes occurs because thiazide-like diuretics such as indapamide are referred to as thiazides despite not having the thiazide chemical structure. When used this way, "thiazide" refers to a drug which acts at the thiazide receptor. The thiazide receptor is a sodium-chloride transporter that pulls NaCl from the lumen in the distal convoluted tubule. Thiazide diuretics inhibit this receptor, causing the body to release NaCl and water into the lumen, thereby increasing the amount of urine produced each day. An example of a molecule that is chemically a thiazide but not used as a diuretic is methylchloroisothiazolinone, often found as an antimicrobial in cosmetics. Medical uses Thiazide diuretics are primarily used to treat the hypertension (high blood pressure) and edema (swelling) caused by water overload as well as certain conditions related to unbalanced calcium metabolism. Water balance Hypertension There are many causes of hypertension (high blood pressure), including advancing age, smoking and obesity. Sometimes the underlying cause of hypertension can not be determined, resulting in a diagnosis of idiopathic hypertension. Regardless of the cause, someone may have very high hypertension without any initial symptoms. Uncontrolled hypertension will eventually cause damage to the heart, kidneys and eyes. Lifestyle changes, including reducing dietary salt, increasing exercise and losing weight can help to reduce blood pressure. Thiazides and thiazide-like diuretics have been in constant use since their introduction in 1958. Decades as a cornerstone of hypertension treatment show how well these drugs perform for most patients. Low-dose thiazides are tolerated as well as the other classes of medications for hypertension, including ACE inhibitors, beta blockers and calcium channel blockers. In general, the thiazides and thiazide-like diuretics reduce the risk of death, stroke, heart attack, and heart failure due to hypertension. Clinical practice guidelines regarding the use of thiazides vary by geographic region. Guidelines in the United States recommend thiazides as a first-line treatment for hypertension (JNC VIII). A systematic review