Pharmacology · Thiazide and thiazide-like diuretics

Hydrochlorothiazide !

A thiazide diuretic, one of the first-line medicines for high blood pressure. It blocks salt reabsorption in the distal tubule.

Updated 2026-11-01

Class: Thiazide and thiazide-like diuretics
Transporter: Na⁺-Cl⁻ cotransporter (NCC) of the distal convoluted tubule
ATC code: C03AA03
WHO Model List of Essential Medicines

Na⁺-Cl⁻ cotransporter (NCC) of the distal convoluted tubuleHydrochlorothiazide

The figure shows hydrochlorothiazide bound to the human NCC, its real target.

Target in 3D: Na⁺-Cl⁻ cotransporter (NCC) of the distal convoluted tubule. PDB structure 9BWT (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Hydrochlorothiazide is secreted into the tubule and blocks the Na⁺-Cl⁻ cotransporter (NCC) of the distal convoluted tubule from the lumen. More sodium and chloride stay in the urine, and the extra sodium that reaches the collecting duct is swapped for potassium, so potassium is lost. It increases calcium reabsorption. Over weeks blood pressure stays lower also because vascular resistance falls.

Hydrochlorothiazide blocks NCC in the distal tubule
Na⁺ and Cl⁻ stay in the urine; more Na⁺ reaches the collecting duct
K⁺ is exchanged and lost; Ca²⁺ reabsorption rises
Less volume and lower vascular resistance: lower blood pressure

Pharmacokinetics

Absorption: Absorbed by mouth
Metabolism: Not metabolised
Elimination: Eliminated quickly by the kidney, mostly unchanged
Half-life: Varies between about 6 and 15 hours

Indications

High blood pressure, alone or combined Arterial hypertension →
Oedema from heart failure, cirrhosis or kidney disease Heart failure →
Prevention of calcium kidney stones with high urinary calcium Kidney stones (urolithiasis) →

Adverse effects

Common

Hypokalaemia and hyponatraemia
High uric acid and gout attacks
Higher blood glucose and lipids
Mild rise in blood calcium
Photosensitivity
Dizziness on standing

Contraindications

Anuria
Hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs

Key interactions

Lithium: Less lithium clearance and risk of toxicity
Digoxin: Hypokalaemia makes digoxin toxicity more likely
Cholestyramine or colestipol: They bind the drug and reduce its absorption
Corticosteroids: More potassium loss
NSAIDs: Weaker diuretic and antihypertensive effect

What is monitored

Sodium, potassium and calcium
Kidney function
Blood pressure
Glucose, lipids and uric acid
Skin checks with long use

Nursing care

Before giving: blood pressure and potassium; report low potassium or sodium.
Watch for confusion, weakness or falls in older adults (hyponatraemia, low pressure).
In diabetes, check blood glucose more closely at the start.
Ask about sudden eye pain or blurred vision: it needs urgent assessment.
Teach: protect skin from the sun, rise slowly, morning intake to avoid waking at night.

Pregnancy and breastfeeding

Not used for ordinary oedema in pregnancy; it crosses the placenta and can cause jaundice or low platelets in the newborn.

Test yourself

Think of the answer, then tap the question to see it.

Why does hydrochlorothiazide cause hypokalaemia?

More sodium reaches the collecting duct, where it is reabsorbed in exchange for potassium, so potassium secretion rises; aldosterone activated by volume loss adds to this.

Which eye emergency can hydrochlorothiazide cause?

Acute myopia with secondary angle-closure glaucoma, an idiosyncratic reaction to the sulfonamide, usually within hours to weeks of starting.

How does hydrochlorothiazide change calcium in the urine?

It lowers it, because it increases calcium reabsorption in the distal tubule; that is why it helps prevent calcium stones.

Which drug's levels rise dangerously when combined with thiazides?

Lithium: thiazides reduce its renal clearance and can cause lithium toxicity.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - HYDROCHLOROTHIAZIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); Hydrochlorothiazide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2021); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); RCSB PDB - 9BWT: human sodium chloride cotransporter NCC S344E in the phosphorylation state and in complex with hydrochlorothiazide (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.