Hydrochlorothiazide: Structure, Properties, Pharmacology, and Safety

Hydrochlorothiazide (HCTZ) is a thiazide diuretic widely used to manage hypertension and edema associated with various medical conditions. Its mechanism of action, chemical properties, and safety profile make it a cornerstone in cardiovascular and renal medicine. This guide provides a detailed overview of Hydrochlorothiazide’s structure, properties, pharmacology, uses, and safety.

1. Structure of Hydrochlorothiazide

The molecular structure of Hydrochlorothiazide underpins its efficacy as a diuretic.

2D Structure

Hydrochlorothiazide’s 2D structure features a benzothiadiazine backbone with sulfonamide groups. These groups are critical for its diuretic action by inhibiting sodium reabsorption in the kidneys.

3D Structure

The 3D conformation of Hydrochlorothiazide highlights its spatial orientation, enhancing its binding to the sodium-chloride symporter in renal tubules. This precise interaction facilitates its ability to promote diuresis and reduce blood pressure.

2. Names and Identifiers

Hydrochlorothiazide is documented under various names and identifiers in medical literature.

• IUPAC Name:
  6-chloro-1,1-dioxo-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
• Molecular Formula:
  C7H8ClN3O4S2
• Molecular Weight:
  297.73 g/mol
• CAS Registry Number:
  58-93-5
• Synonyms:
  HCTZ, Hydrodiuril, Microzide

These identifiers facilitate the recognition of Hydrochlorothiazide in pharmacological databases.

3. Chemical and Physical Properties

The chemical and physical properties of Hydrochlorothiazide contribute to its therapeutic effectiveness.

These properties allow Hydrochlorothiazide to be formulated for oral administration.

4. Drug and Medication Information

Hydrochlorothiazide is widely used for managing cardiovascular and renal conditions.

Formulations

• Oral Tablets and Capsules:
  • Available in strengths of 12.5 mg, 25 mg, and 50 mg.
• Combination Medications:
  • Frequently combined with other antihypertensive drugs like lisinopril or losartan.

Mechanism of Action

Hydrochlorothiazide works by:

• Inhibiting Sodium Reabsorption: Blocks the sodium-chloride symporter in the distal convoluted tubules of the kidney.
• Promoting Diuresis: Increases sodium and water excretion, reducing blood volume and pressure.
• Lowering Peripheral Vascular Resistance: Contributes to its antihypertensive effect over time.

Dosage and Administration

• For Hypertension: 12.5-25 mg orally once daily.
• For Edema: 25-100 mg daily in one or two divided doses.

Follow your healthcare provider’s instructions for optimal results.

5. Pharmacology and Biochemistry

Hydrochlorothiazide’s pharmacology underlines its role in managing hypertension and fluid overload.

Pharmacokinetics

• Absorption:
  Rapidly absorbed after oral administration, with bioavailability of ~70%.
• Onset of Action:
  Diuresis begins within 2 hours of administration.
• Half-Life:
  6-15 hours, depending on renal function.
• Excretion:
  Primarily excreted unchanged in urine.

Pharmacodynamics

Hydrochlorothiazide decreases sodium and fluid retention, which reduces blood volume. It also relaxes blood vessels, leading to a sustained antihypertensive effect.

6. Uses and Side Effects

Primary Uses

• Hypertension:
  First-line treatment for high blood pressure, often in combination with other drugs.
• Edema:
  Manages fluid retention due to heart failure, liver disease, or kidney disorders.
• Calcium Nephrolithiasis Prevention:
  Reduces calcium excretion in urine to prevent kidney stones.

Benefits

• Effective in lowering blood pressure and preventing cardiovascular events.
• Reduces swelling and fluid overload.
• Minimal systemic effects at low doses.

Side Effects

Common side effects include:

• Dizziness or lightheadedness.
• Increased urination.
• Electrolyte imbalances (e.g., low potassium or sodium).

Rare but serious side effects:

• Severe dehydration.
• Allergic reactions like rash or swelling.
• Increased blood sugar or uric acid levels.

Consult your doctor if side effects persist or worsen.

7. Safety and Hazards

Safety Profile

Hydrochlorothiazide is generally safe when used as prescribed. However:

• Contraindications: Not suitable for patients with severe kidney disease, anuria (absence of urine), or hypersensitivity to sulfonamides.
• Pregnancy and Breastfeeding: Use with caution; consult your doctor before use.

Chemical Safety

Handling Precautions

• Store in a cool, dry place away from sunlight.
• Keep out of reach of children.

Environmental Impact

Hydrochlorothiazide is excreted in urine and may persist in aquatic systems. Proper disposal is recommended to minimize environmental impact.