Hydrochlorothiazide is a diuretic drug and is considered the prototype of thiazide diuretics. The active ingredient is used, among other things, to treat edema.
What is hydrochlorothiazide?
Hydrochlorothiazide acts on the distal tubules of the nephron. The nephron is the smallest functional unit of the kidney. Hydrochlorothiazide is a diuretic. Diuretics are drugs with a fairly high therapeutic range. They are mainly used to flush water out of the human body. Among diuretic drugs, a distinction can be made between different types. Thiazide diuretics, along with potassium-sparing diuretics and aldosterone antagonists, are among the best-known diuretics. Thiazide diuretics such as hydrochlorothiazide have a wide range of applications. Among other things, they are used to treat high blood pressure or heart failure. The thiazide diuretics are usually well tolerated, but can also result in electrolyte disturbances due to their flushing-out effect. Hydrochlorothiazide has been banned for athletes by the World Anti-Doping Agency. Although the drug does not directly enhance performance, it is one of the so-called masking agents. These can make it more difficult to detect doping substances. Hydrochlorothiazide dilutes the urine to such an extent that a doping control in the urine is hardly possible.
Pharmacologic effect
Hydrochlorothiazide acts on the distal tubules of the nephron. The nephron is the smallest functional unit of the kidney. It consists of a renal corpuscle and an attached tubular system called the tubule system. The primary urine is filtered in the nephron. In the tubular system, water and various other substances are recovered before the so-called secondary urine is then excreted via the draining urinary tract. Hydrochlorothiazide inhibits the sodium–chloride cotransporter at the luminal membrane of the cells in the tubular system. In higher doses, the drug additionally inhibits carbonic anhydrase. As a result, the kidneys excrete more sodium chloride and thus also water. In addition, fewer calcium ions and more magnesium ions are excreted. Hydrochlorothiazide can therefore also lead to increasing bone density in patients with osteoporosis due to the increased calcium retention. The bioavailability of hydrochlorothiazide is 70 percent. The duration of action is 6 to 12 hours. Thereafter, the active ingredient is excreted almost unchanged by the kidneys.
Medical use and application
Hydrochlorothiazide is used primarily to treat essential arterial hypertension. Rarely, however, is the agent administered solitarily. Most often, therapy is in combination with beta-blockers or ACE inhibitors. Hydrochlorothiazide is also used in heart failure. Here, the drug is usually used in combination with loop diuretics. These serve to mobilize edema, whereas hydrochlorothiazide serves to excrete water. Since hydrochlorothiazide increases the retention of calcium ions, it is also used in the treatment of osteoporosis. The recovered calcium can increase patients’ bone density. Another indication for the use of hydrochlorothiazide is hypercalciuria. This is an increased excretion of calcium through the urine. Bone metastases, vitamin D intoxications, sarcoidosis or Bartter’s syndrome are possible causes of such hypercalciuria. Because urinary stones may occur due to increased calcium excretion, hydrochlorothiazide is used prophylactically in these cases.
Risks and side effects
Basically, hydrochlorothiazide is well tolerated, but due to the electrolyte losses, various side effects may develop. Decreased blood potassium and sodium levels are common. Magnesium and chloride are also decreased. On the other hand, the level of calcium in the blood is increased. Dry mouth and thirst are typical side effects. At higher doses, weakness, dizziness, muscle pain and muscle cramps may also occur. Patients suffer from palpitations and decreased blood pressure. Especially when changing from lying to standing, they show orthostatic regulation disorders with dizziness. At a high dosage, urinary excretion can be very excessive. As a result of dehydration and hypovolemia, i.e., decreased circulating blood volume, thickening of the blood occurs.Especially in elderly patients or in patients with venous disease, the risk of developing thrombosis or embolism is increased as a result. As a result of hypokalemia, fatigue, abnormal drowsiness, paralysis, or sensory disturbances may occur. Constipation and flatulence are also common side effects of hydrochlorothiazide. Elevated blood uric acid levels may occur during treatment, ultimately leading to gout attacks. Furthermore, an increase in blood lipids (triglycerides and cholesterol) is frequently observed. Occasionally, the urinary substances creatinine and urea also rise in the blood. A feared side effect of therapy with hydrochlorothiazide is pancreatitis. The inflammation of the pancreas can be life-threatening. Rarely, allergic skin reactions such as itching, exanthema or wheals occur when taking hydrochlorothiazide. Acute kidney inflammation, vascular inflammation, and anemia are also among the rare side effects. Some patients may also develop impotence or visual disturbances while taking hydrochlorothiazide. Thiazide diuretics such as hydrochlorothiazide should not be used in severe renal or hepatic impairment. Severe electrolyte disturbances such as hypokalemia, hyponatremia, and hypercalcemia are also contraindications. The use of hydrochlorothiazide is dangerous in digitalisin intoxications and in cardiac arrhythmias. Similarly, hydrochlorothiazide should not be used in case of allergy to sulfonamides. Also, during pregnancy and lactation, the physician should ideally prescribe a different diuretic.
