Pathophysiology and Mechanism of Action
Blood pressure regulation is inextricably linked to the circulating blood volume (CBV). Volume receptors located in the atria and pulmonary vessels respond to stretch and transmit afferent impulses via the medulla oblongata to the hypothalamus. This triggers a hormonal response:
- The neurohypophysis increases the secretion of antidiuretic hormone (vasopressin), leading to water retention and vasospasm.
- The release of natriuretic peptides (types A, B, and C) decreases, which also leads to enhanced reabsorption of sodium and water, and vascular spasm.
The hypotensive effect of diuretics has a dual mechanism. First, they reduce CBV. Second, they induce vasodilation, which is considered the decisive factor. The pathogenesis of vasodilation is as follows:
- Elimination of excess sodium from the body.
- Reduction of sodium concentration directly within the vascular wall (decreasing angiomyocyte "overload").
- Reduction of transmembrane calcium ion transport into the cell.
- Reduction of vascular wall hyperreactivity to vasoconstrictive stimuli.
- Vasodilation $\rightarrow$ drop in total peripheral resistance (TPR) $\rightarrow$ decrease in blood pressure.
Main Drugs and Their Characteristics
Several main classes of diuretics are used in the pharmacotherapy of hypertension: thiazides, thiazide-like drugs, loop diuretics, and aldosterone antagonists.
Thiazide-like Diuretics A prominent representative is Indapamidum (indapamide). This is a non-thiazide sulfonamide derivative. The drug is rapidly and completely absorbed orally, reaching peak concentrations in 1–2 hours. The 18-hour half-life ensures a prolonged effect.
- Dosing feature: At the therapeutic dose (2.5 mg/day), indapamide exerts virtually no diuretic effect. Blood pressure drops exclusively due to the reduction in TPR. Increasing the dose does not enhance the hypotensive effect, but it does provoke marked diuresis.
Thiazide and Loop Diuretics
- Hydrochlorothiazide: A classic thiazide drug for systematic treatment. It is frequently used in combination products.
- Furosemide: A loop diuretic. When administered intravenously, it can rapidly lower blood pressure. This effect is not related to fluid loss, but to a direct venodilating action, which instantly reduces cardiac preload.
Place in Therapy and Management of Side Effects
Diuretics are prescribed both as monotherapy (thiazides are drugs of choice in early-stage hypertension) and in combination regimens. The rationale for combination therapy is straightforward: most other antihypertensive medications cause a compensatory retention of water and electrolytes. Diuretics successfully counteract this effect, potentiate the action of concomitant therapy, and normalize the electrolyte balance of the vascular wall.
The Problem of Electrolyte Loss Loop, thiazide, and thiazide-like agents share a common side effect—they cause hypokalemia and hypomagnesemia. Orthostatic hypotension may also occur during treatment. To correct electrolyte disturbances, clinicians use:
- Supplementation with potassium and magnesium preparations.
- Combination with potassium- and magnesium-sparing diuretics: triamterene or aldosterone antagonists (spironolactone).
Drugs for Special Clinical Situations
In acute heart failure, specific classes of drugs are used: natriuretic peptide analogs, endothelin antagonists, and vasopressin antagonists.
To manage hypertensive emergencies, direct myotropic agents that directly relax vascular smooth muscle may be used:
- Bendazol: Produces a moderate and short-lived effect, most often used in combinations.
- Magnesium sulfate: Administered intramuscularly. Major risk: intravenous administration of magnesium sulfate can cause dangerous depression of the respiratory center.