EpistemisHydrochlorothiazide (HCTZ)
Common trade names: Esidrex, Hidroasal, microzide.
Mechanism
Pharmacological Group
Thiazidic diuretic derived from benzothiadiazines.
Mechanism of Action
It selectively and reversibly inhibits the apical sodium and chloride symporter cotransporter NCC in the luminal membrane of the Distal Convoluted Tubule (TCD), blocking the coordinated reabsorption of these electrolytes:
This increases urinary excretion of sodium and chloride. By blocking NCC, the intracellular sodium concentration in the TCD cell decreases. This stimulates the basolateral sodium-calcium exchanger (NCX), which introduces Na+ from the interstitium and introduces Ca2+ back from the cytoplasm. This intracellular calcium depletion promotes greater opening of epithelial apical calcium channels (TRPV5), netly increasing active transcellular calcium reabsorption. Therefore, thiazides retain calcium and reduce its urinary excretion (hypocalciuria).
Pharmacokinetics
Key Pharmacokinetics
- Administration: Orally only.
- Absorption: Rapid but incomplete (60-70% bioavailability).
- Protein binding: 60-70%.
- Metabolism: Does not undergo hepatic metabolism; remains unchanged.
- Excretion: Renal elimination by filtration and active tubular secretion mediated by OAT.
- Half-life: 6 to 15 hours.
Indicators and dose
Clinical Indications
- Essential arterial hypertension: First line of choice, frequently in combination therapy with ACEI or ARB.
- Mild-moderate edema associated with HF or nephropathies.
- Idiopathic hypercalciuria (calcium nephrolithiasis): Of choice to reduce supersaturation and precipitation of calcium salts in the urine.
- Nephrogenic diabetes insipidus: Paradoxically, it reduces free urinary volume by causing a mild depletion of plasma volume, which overstimulates the reabsorption of water and sodium in the TCP (reducing the delivery of water to the collecting duct).
Dosage and Settings
- Hypertension: 12.5 mg to 25 mg once a day. Doses greater than 50 mg do not increase the antihypertensive effect but do increase metabolic alterations.
- Nephrolithiasis / Edema: 50 mg to 100 mg daily.
- Renal adjustment: Loses diuretic efficacy when CrCl falls below 30 mL/min. At these filtration rates, the amount of drug secreted into the lumen is insufficient to block NCC clinically effectively.
Security
Contraindications
- Absolute: Severe anuria; hypersensitivity to thiazides or sulfonamides; active gout; Intractable hypokalemia or hyponatremia.
Adverse Effects (ADR)
- Common: Hypokalemia, severe hyponatremia (especially in elderly women with low body weight, due to induction of ADH secretion and selective retention of free water), mild hypomagnesemia.
- Metabolic: Transient mild hypercalcemia, hyperuricemia with risk of gout, hyperglycemia (hypokalemia decreases insulin secretion by the beta cells of the pancreas), moderate range dyslipidemia.
Interactions
- Drugs that prolong the QT interval (e.g. Amiodarone, Sotalol, Terfenadine): Induced hypokalemia precipitates fatal torsades de pointes.
- Oral antidiabetics (e.g. Metformin, Sulfonylureas): Reduction in hypoglycemic efficacy due to the hyperglycemic effect of the thiazide.
Pregnancy and Breastfeeding
Category B. It is not considered first line for gestational hypertension or preeclampsia due to the risk of reducing the physiological plasma volume necessary for placental perfusion. It is excreted in breast milk in small quantities.
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Renal and Diuretics
- Cluster
- Classic Thiazide Diuretic