Hydrochlorothiazide

Mechanism of action

The drug belongs to the group of thiazide diuretics. Its main target is the epithelium of the initial segment of the distal convoluted tubules of the kidneys.

Hydrochlorothiazide inhibits the sodium and chloride ion cotransport. By blocking sodium ion reabsorption in the renal tubules, the drug leaves them in the nephron lumen. Following the osmotic gradient, sodium "pulls" water along with it, leading to increased diuresis and the elimination of excess fluid from the body.

Pharmacokinetics and dosing schedule

The drug is well absorbed from the gastrointestinal tract when taken orally.

• Onset of action: the diuretic effect develops fairly quickly — within 30–60 minutes after administration.
• Peak effect: the maximum action is registered after 2 hours.
• Duration: the effect lasts from 8 to 12 hours.

Prescribing guidelines: According to the reference guide, the drug is available in 0.025 g tablets. It is prescribed orally, after meals. The dosing regimen is once in the morning, with the dose ranging from 1 to 4 tablets depending on the clinical situation. Morning administration is justified by pharmacokinetics: the 12-hour action will end by evening without disrupting the patient's night sleep.

Indications for use

Hydrochlorothiazide has a wide range of applications. It is prescribed for the following conditions:

1. Arterial hypertension (AH): It is a first-line drug. Highly effective for the systematic treatment of essential hypertension, it can be used as monotherapy.
2. Edematous syndrome: A standard indication for eliminating excess fluid.
3. Diabetes insipidus: Used due to its paradoxical antidiuretic effect (reduces the volume of excreted urine, although the exact mechanism of this phenomenon is not fully understood).
4. Nephrolithiasis (urolithiasis): The drug affects calcium metabolism. It reduces the content of $Ca^{2+}$ ions in the urine, preventing the formation of insoluble calcium salts in the renal filtrate, which serves as an excellent prevention of stone formation.

Side effects

The spectrum of adverse reactions of hydrochlorothiazide requires careful monitoring of the patient's condition. The main side effects are divided into three groups:

• Electrolyte disturbances: The drug actively excretes ions, leading to hypokalemia and hypomagnesemia.
• Metabolic disorders: It can cause uric acid retention in the body, provoking hyperuricemia. Also, an increase in blood glucose levels—hyperglycemia—is possible during administration.
• General and dyspeptic disorders: Patients may complain of nausea and general weakness.

Role in combination therapy

In clinical practice, hydrochlorothiazide is very frequently used as part of fixed-dose combination medicinal products. This ensures synergism of action and convenience of administration.

Classic examples of combinations (predominantly based on the sympatholytic reserpine):

• Adelphane-Esidrex: Triple combination (Reserpine + vasodilator dihydralazine + hydrochlorothiazide 0.01 g).
• Adelphane-Esidrex-K and Triresid K: Quadruple combinations. Potassium chloride (at a dose of 0.6 g) is added to the previous composition specifically to correct the electrolyte balance and prevent hypokalemia caused by the thiazide.
• Crystepin: Alternative combination (Reserpine + ergot alkaloid dihydroergotoxin + diuretic clopamide, which belongs to thiazide-like agents).

Also, in the tactics of diuretic therapy, it is important to consider drug interactions. For example, for rapid fluid removal, a loop diuretic (furosemide) is prescribed together with a potassium-sparing one (spironolactone). As the slow effect of spironolactone develops, the loop diuretic is discontinued, and baseline therapy may be continued with thiazides.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Comparative pharmacodynamics of thiazide and loop diuretics
• Mechanisms of development of hyperuricemia and hyperglycemia during thiazide administration
• Paradoxical antidiuretic effect in diabetes insipidus
• Principles of creating fixed antihypertensive combinations
• Classification of antihypertensive agents by mechanism of action

Other topics in the «Drugs and Prescriptions» section

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