Hydrochlorothiazide

Products

Hydrochlorothiazide is commercially available in numerous antihypertensive agents in combination with ACE inhibitors, sartans, renin inhibitors, potassium-sparing diuretics, calcium channel blockers, and beta blockers. Use as a monopreparation (Esidrex) is less common. Hydrochlorothiazide has been approved in many countries since 1958.

Structure and properties

Hydrochlorothiazide (C7H8ClN3O4S2, Mr = 297.7 g/mol) is a white crystalline powder that is very sparingly soluble in water. It has a sulfonamide-like structure. Hydrochlorothiazide is structurally closely related to the first thiazide chlorothiazide.

Effects

Hydrochlorothiazide (ATC C03AA03) has diuretic, urine-thinning, and antihypertensive properties. The effects are due to inhibition of reabsorption of sodium chloride at the distal tubule of the renal nephron. This also increases the excretion of potassium, protons (H+), and water. Hydrochlorothiazide promotes the reabsorption of calcium.

Indications

  • Hypertension
  • Heart failure
  • Edema
  • Renal diabetes insipidus
  • Idiopathic hypercalcuria and for recurrence prophylaxis of calcium-containing stones.

Abuse as a doping agent

Hydrochlorothiazide is banned in many countries as a so-called “masking” agent in competitive sports because it obscures the detection of doping agents by its urine-thinning effect. Hydrochlorothiazide, as an organic anion, can also reduce the secretion of other agents with a negative charge.

Dosage

According to the drug label. It is usually taken in the morning. The skin should be protected from sunlight during treatment (see below).

Contraindications

  • Hypersensitivity to hydrochlorothiazide and other sulfonamide derivatives (eg, some diuretics, antibiotics)
  • Hypokalemia resistant to therapy
  • Hyponatremia
  • Hypercalcemia
  • Symptomatic hyperuricemia (gout, urate stones).
  • Pregnancy
  • Renal insufficiency

Full precautions can be found in the drug label.

Adverse effects

The most common adverse effect of monotherapy is hypokalemia due to increased excretion of potassium ions. Occasionally, other electrolyte and metabolic disturbances occur, such as hyponatremia, hypomagnesemia, hyperglycemia, and hyperuricemia. Lowering of blood pressure may cause orthostatic hypotension with headache and dizziness. Skin reactions such as urticaria, erythema, pruritus, photosensitivity to severe skin reactions may develop (toxic epidermolysis, lupus erythematosus). Numerous other, less frequent adverse effects are possible. In epidemiological studies, an increased risk of non-melanocytic malignancies of the skin and lips in the form of basal cell and squamous cell carcinomas has been observed with increasing cumulative hydrochlorothiazide exposure. Photosensitivity is a possible trigger. Patients should check their skin regularly and report suspicious lesions to the physician. Skin should be protected from excessive sun exposure.