Chlorthalidone, is a diuretic medication used to treat high blood pressure, swelling including that due to heart failure, liver failure, and nephrotic syndrome, diabetes insipidus, and renal tubular acidosis.

In high blood pressure it is a preferred initial treatment.

It is also used to prevent calcium-based kidney stones.

It is taken by mouth.

Effects generally begin within three hours and last for up to three days.

It is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

Pregnancy category AU: C

Routes of administration By mouth

Thiazide diuretic

Protein binding 75%

Elimination half-life 40 hours

Excretion Kidney

Side effects: low blood potassium, low blood sodium, high blood sugar, dizziness, and erectile dysfunction.

Other side effects may include gout, low blood magnesium, high blood calcium, allergic reactions, and low blood pressure.

It  increases the amount of sodium and water lost by the kidneys.

It is effective in people with kidney disease.

It is used to treat left ventricular hypertrophy in the heart, by lowering blood pressure, and thereby reducing systemic vascular resistance. 

It is superior to hydrochlorothiazide for reducing the mass of the left ventricle of the heart in persons with enlargement of the left ventricle of the heart.

It  is superior to angiotensin converting enzyme Inhibitors or angiotensin II receptor blockers for inducing regression of enlargement of the left ventricle, which is the main pumping chamber of the heart.

It may improve edema by increasing urinary salt and water excretion, lowering intravascular hydrostatic pressure and thereby lowering transcapillary pressure.

Regardless of the cause of edema chlorthalidone may sometimes reduce the severity of edema by reducing intravascular volume and thereby reducing intravascular hydrostatic pressure.

Chlorthalidone decreases mineral bone loss by promoting calcium retention by the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.

Thiazide exposure is associated with a reduced risk of hip fracture.

Chlorthalidone reduces the amount of calcium excreted in urine, reducing the risk of calcium oxalate kidney stones.

In people who have had multiple episodes of calcium oxalate kidney stones, chlortalidone lowers the risk of having another episode of kidney stones.

Chlorthalidone is more effective than hydrochlorothiazide for lowering urine calcium levels and is therefore probably more effective.

Chlorthalidone reduces the volume of endolymph and thereby reduces the pressure in the inner ear chambers.

Elevated endolymph pressure in the inner ear is thought to be the cause of Ménière’s disease.

Chlorthalidone and other thiazide medications are key component of treatment of nephrogenic diabetes insipidus. 

Nephrogenic diabetes insipidus occurs when the kidney is unable to produce concentrated urine because it has an inadequate response to vasopressin-dependent removal of free water from the renal tubular filtrate. 

By blocking sodium ion resorption in the distal convoluted tubule, chlorthalidone induces an increase in excretion of sodium ion in urine, termed natriuresis.

Giving chlorthalidone while 

 restricting dietary sodium intake causes low intravascular volume, which induces isotonic reabsorption of solute from the proximal renal tubule

Chlorthalidone reduces  solute delivery in the renal collecting tubule and renal medullary collecting duct, which allows increased water resorption and higher concentration of urine, which leads to reversal of nephrogenic diabetes insipidus by a means that is independent of vasopressin.

In the CLICK trial Chlorthalidone was found to be in affective blood pressure lowering agent in patients with advanced chronic kidney disease.

Adverse effects: 

Hypokalemia occurs occasionally; the risk of hypokalemia is higher in persons who are magnesium deficient.

Hypomagnesemia occurs  in 20% of persons within a few weeks of beginning treatment with   chlorthalidone 50 mg of  daily.

The risk of chlorthalidone-associated hypomagnesemia is higher in persons with diabetes mellitus who have low dietary magnesium intake.

Hyponatremia occurred in 4.1% of subjects randomized to chlorthalidone in the Systolic Hypertension in the Elderly Trial, compared to 1.3% of control subjects.

The risk of hyponatremia varies from 5 per 100,000 person-years for those younger than 40 years of age to 730 per 100,000 person-years in those older than 80 years of age.

In Blacks chlorthalidone was not associated with a significant blood pressure lowering benefits over hydrochlorothiazide, while it was associated with a greater risk of metabolic adverse effects.

Hyponatremia is more likely in persons with certain genetic variants of the prostaglandin transporter SLCO2A1.

Thiazide-associated hyponatremia is often more severe than loop diuretic-associated hyponatremia.

Hypercalcemia can occur in normal persons exposed to chlorthalidone but is more likely to occur when persons with sub-clinical hyperparathyroidism.

Hyperuricemia may occur.

Hyperglycemia, high blood sugar is more common in persons who are magnesium deficient.

Hyperlipidemia, high cholesterol and triglycerides, may occur.




Photoonycholysis detachment of nails from nailbed with sun exposure.

Weight gain

Gout with approximately double the risk.


The frequency and severity of adverse effects is much reduced when used at lower doses.

Chlorthalidone reduces reabsorption of sodium and chloride primarily through inhibition of the Na+/Cl− symporter in the apical membrane of distal convoluted tubule cells in the kidney.

It is unlike thiazide diuretics in that, in addition to its inhibition of the Na+/Cl− symporter, it also strongly inhibits multiple isoforms of carbonic anhydrase.

Some of its diuretic effect is also due to this inhibition of carbonic anhydrase in the proximal tubule.

Chronic exposure decreases the glomerular filtration rate, and its diuretic effect is diminished in persons with kidney impairment. 

By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism, resulting in a low blood concentration of potassium and chloride as well as a mild metabolic alkalosis.

The diuretic effect of Chlorthalidone is not affected by the acid-base balance of the person being treated.

Initially diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. 

Ultimately, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. 

The reduced  intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.

Chlorthalidone is slowly absorbed from the gastrointestinal tract after oral ingestion. 

It has a long half-life and a prolonged diuretic action.

Its prolonged action may account for the higher efficacy of Chlorthalidone compared to the shorter half-life medication, hydrochlorothiazide. 

Chlorthalidone is eliminated from the body mostly by the kidney, as an unchanged drug. 

With diminished kidney function, the clearance of Chlorthalidone is reduced and the elimination half-life is increased.

It crosses the placenta and is excreted in breast milk.

It may suppress lactation.

It  accumulate in newborns via breast milk, despite receiving only about 6% of the maternal weight-adjusted dose.

Chlorthalidone lacks the benzothiadiazine structure of the thiazide-type diuretics, it is called a thiazide-like diuretic.

In a large pragmatic trial of thiazide diuretics and doses commonly used, patient who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer related deaths than patients who received hydrochlorothiazide (Ishani A).

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