What is the Difference Between Hydrochlorothiazide and Chlorthalidone

The key difference between hydrochlorothiazide and chlorthalidone is that hydrochlorothiazide has a shorter half-life and may require multiple daily doses for comparable effects, while chlorthalidone has a longer half-life, provides a more sustained and potent effect, and often requires once-daily dosing.

Hydrochlorothiazide and chlorthalidone are thiazide diuretics used to treat hypertension (high blood pressure) and edema (fluid retention). They increase urine production and reduce fluid retention in the body. Both medications are generally well-tolerated and have a similar mechanism of action in inhibiting sodium reabsorption in the kidneys.

CONTENTS

1. Overview and Key Difference
2. What is Hydrochlorothiazide 
3. What is Chlorthalidone
4. Similarities – Hydrochlorothiazide and Chlorthalidone
5. Hydrochlorothiazide vs Chlorthalidone in Tabular Form
6. Summary – Hydrochlorothiazide vs Chlorthalidone

What is Hydrochlorothiazide?

Hydrochlorothiazide is a widely used thiazide diuretic prescribed for hypertension and edema. It promotes the excretion of water and electrolytes, reducing blood volume and lowering blood pressure through the inhibition of the reabsorption of sodium and chloride in the kidneys. The drug is taken orally since it comes in tablet or capsule form, with dosage determined by individual needs. Side effects may include increased urination, electrolyte imbalances, dizziness, and mild gastrointestinal disturbances, while severe reactions are rare. Monitoring blood pressure and electrolyte levels is essential during treatment.

Hydrochlorothiazide is a chemical compound with the molecular formula C₇H₈ClN₃O₄S₂. Chemically, hydrochlorothiazide is a benzothiadiazine derivative with a chlorine atom substituted at the 6-position. It contains a sulfonamide group (-SO₂NH₂) and a diuretic thiazide ring system. These chemical properties contribute to its pharmacological activities as a diuretic agent.

What is Chlorthalidone?

Chlorthalidone is another thiazide diuretic drug frequently administered to treat hypertension and edema. Chlorthalidone causes the kidneys to excrete more water and electrolytes like salt and chloride. As a result, it often allows for a once-daily dose and has a usually well-tolerated, powerful impact. Because chlorthalidone has a longer half-life than other thiazide diuretics, its activity lasts longer.

Chlorthalidone is a chemical compound with the molecular formula C₁₄H₁₁ClN₂O₄S. It is a sulfonamide derivative and a kind of diuretic similar to thiazides. The benzene ring in chlorthalidone has a chlorine atom replaced at position 2 and a sulfonamide group (-SO₂NH₂) substituted at position 5. A fused bicyclic structure with a hydroxyl group (-OH) at the first position and a ketone group (=O) at the third position makes up the isoindoline moiety also present in the compound. The pharmacological actions of chlorthalidone are influenced by these chemical characteristics, which enable it to block the reabsorption of electrolytes in the kidney and exert its diuretic and antihypertensive qualities.

What are the Similarities Between Hydrochlorothiazide and Chlorthalidone?

• Both hydrochlorothiazide and chlorthalidone are a group of drugs in the thiazide diuretic family.
• They work by increasing the excretion of water and electrolytes through the kidneys, which reduces blood volume and lowers blood pressure.
• Both drugs may have similar side effects, such as increased urination, electrolyte imbalances, dizziness, and gastrointestinal disturbances.
• Both are generally taken orally as pills or capsules, and the doses may change according to the characteristics and reaction of each patient to therapy.

What is the Difference Between Hydrochlorothiazide and Chlorthalidone?

Hypertension and edema are usually treated with hydrochlorothiazide and chlorthalidone. There are, however, several differences between the two medications. There is a significant difference between hydrochlorothiazide and chlorthalidone in terms of their chemical composition, duration of action, frequency of doses, potency, therapeutic impact, rate of absorption, and selectivity. While chlorthalidone possesses an isoindoline moiety, hydrochlorothiazide possesses a benzothiadiazine ring system. The half-life of hydrochlorothiazide is shorter (12–16 hours); thus, it is frequently administered once or twice a day. Contrarily, chlorthalidone is advised for once-daily therapy because of its lengthy half-life (48–72 hours).

Moreover, chlorthalidone is more efficient than hydrochlorothiazide and considerably lowers blood pressure. However, chlorthalidone is slowly absorbed, whereas hydrochlorothiazide is quickly absorbed. In addition, hydrochlorothiazide is associated with a lower risk of estimated glomerular filtration rate (eGFR), lower cardiovascular events, and potassium (hypokalemia) compared to chlorthalidone.

The below infographic presents the differences between hydrochlorothiazide and chlorthalidone in tabular form for side-by-side comparison.

Summary – Hydrochlorothiazide vs Chlorthalidone

Hydrochlorothiazide and chlorthalidone are thiazide diuretics used for treating hypertension and edema but differ in various aspects. Hydrochlorothiazide has a benzothiadiazine ring system, while chlorthalidone has an isoindoline moiety. The duration of action is shorter for hydrochlorothiazide (12-16 hours) compared to chlorthalidone (48-72 hours). Hydrochlorothiazide is usually taken once or twice daily, while chlorthalidone is prescribed for once-daily dosing. Chlorthalidone is more potent, requiring a lower dose, and provides a more significant reduction in hypertension. Moreover, hydrochlorothiazide is rapidly absorbed, while chlorthalidone is absorbed slowly. Hydrochlorothiazide can be taken with or without food, while the absorption of chlorthalidone is reduced when taken with food. In brief, this difference between hydrochlorothiazide and chlorthalidone, as seen in their chemical structure, duration of action, dosage frequency, potency, and absorption, contribute to the variations in their clinical use.

Reference:

1. Edwards, Cedric, et al. “Comparison of Clinical Outcomes and Safety Associated with Chlorthalidone vs Hydrochlorothiazide in Older Adults with Varying Levels of Kidney Function.” JAMA Network Open, vol. 4, no. 9, 2021.

Image Courtesy:

1. “Hydrochlorothiazide-2D-skeletal” By Ben Mills – Own work (Public Domain) via Commons Wikimedia