Two Blood Pressure Drugs

blood pressure drugs

Thiazide diuretics have been used to treat hypertension since the late fifties. Due to their cost-effectiveness profile and efficacy, they remain one of the most important drugs used to lower blood pressure. As stated by drugstore reviews, these diuretics were first-tolerated and efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in clinical studies.

However, the use of beta-blockers and diuretics as antihypertensive drugs has known a dramatic decline since the early 1980s to the early 1990s with the introduction of calcium channel blockers and ACE inhibitors. Nevertheless, the thiazide diuretics such as hydrochlorothiazide and chlorthalidone are still the first-line therapy to treat arterial hypertension.

Hydrochlorothiazide and Chlorthalidone

Thiazide diuretics are one of the most preferred pharmacologic treatments for hypertension. According to drugstore reviews, chlorthalidone and hydrochlorothiazide have been the two most commonly used diuretics in major clinical trials. Treatment guidelines consider these two drugs interchangeable agents within the class of thiazide or thiazide-like drugs. Many pharmacists list them as equipotent.


Despite these beliefs, some suggest cardiovascular effects differ between these two drugs. The drugstore reviews conducted research from 1966 to 2004 to identify studies that evaluated these two drugs’ blood pressure-lowering effects and pharmacokinetics. There are significant pharmacodynamics and pharmacokinetic differences between these diuretics. Chlorthalidone is about 1.5 to 2.0 times as potent as hydrochlorothiazide, and chlorthalidone has a much longer duration of action.

Mechanism of Action

Thiazide diuretics prevent the reabsorption of sodium and chloride, blocking the Na+/Cl- transporter in the distal convoluted tubule of the kidney. The drug’s mechanism of action is the same, but they differ in pharmacokinetic profile. Hypertension is a complex syndrome consisting of multiple neuroendocrine, hemodynamic, and metabolic abnormalities. The goals of treatment in hypertension are to reduce cardiovascular morbidity and mortality and to optimally control high blood pressure using the most suitable therapy available. Both hydrochlorothiazide and chlorthalidone have proven anti hypertensive effects.

safety outcomes

Chemistry of These Drugs

Hydrochlorothiazide (HCTZ) belongs to benzothiadiazine class, and they are referred as thiazide diuretics. Benzothiazidines were developed to find more potent carbonic anhydrase inhibitors. The prototype thiazide diuretic was chlorothiazide, but this drug is not used today because of poor bioavailability.

chemical structure

HCTZ has the chemical name 2h-1,2,3-benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-, 1,1-dioxide. HCTZ has a single additional hydrogen substituted on the nitrogen atom on the sulfonamide ring as compared to chlorothiazide. All thiazide diuretics have a similar dual-ring structure.

Though commonly known as a thiazide, chlorthalidone is not a benzothiadiazole and is more appropriately known as a thiazide-like diuretic. Although it is chemically related to sulfonamide, its chemical structure is unique. The chemical name for chlorthalidone is benzenesulfonamide, 2-chloro-5-2,3-dihydro-1-1hydroxy-3-3oxo-1H-isiindol-1-yl.

Pharmacokinetics and Pharmacodynamics

Pharmacokinetic differences are mostly responsible for differences in clinical effects within a given drug class. The pharmacokinetic parameters differ at steady state, especially in older patients, in patients of renal insufficiency, or with drug-drug interactions. Another important aspect of antihypertensive drugs is that their pharmacodynamic response is much longer than their half-life would predict. That’s why most antihypertensives drugs can be given once or twice a day despite half-lives that would predict more frequent dosing.


The sources of drugstore reviews continue to list the half-life of hydrochlorothiazide as short as 2.5 hours. Studies, however, have revealed that the half-life and duration of HCTZ are much longer. After a single oral dose, HCTZ can achieve peak concentration in about 2 hours and has a half-life of about 6.5 to 9 hours. The half-life of HCTZ would be 8 to 15 hours with long-term dosing. This half-life of HCTZ suggests that the drug should be given twice daily. However, several studies support once-daily dosing of HCTZ.



Chlorthalidone serum concentration peaks in about 2 to 6 hours after oral administration. It rapidly enters and concentrates in the erythrocytes. The researchers have found 7 to 10 times greater concentration of chlorthalidone in erythrocytes than in plasma. One possible explanation for the long half-life is that it concentrates in erythrocytes and is slowly released. The natriuretic effect of chlorthalidone is maximum at 18 hours and lasted more than 48 hours in the study of the drug.


Comparison of Action of Both Drugs

According to drugstore reviews, chlorthalidone lowers systolic and diastolic pressure better than hydrochlorothiazide. Even after chlorthalidone and HCTZ achieve the same blood pressure, chlorthalidone lowers the risk of cardiovascular events such as heart attack by approximately 20% more than HCTZ.

equivalent doses

Research shows that chlorthalidone decreases the size of the left ventricle wall more than HCTZ does. However, both drugs have the same effect on blood sugar, cholesterol, sodium and potassium levels. Chlorthalidone is the preferred diuretic because of its longer duration of action. HCTZ has remained so popular despite being second to chlorthalidone in effectiveness because of its availability in different combination pills.


HCTZ and chlorthalidone both are considered as thiazide diurectics. They act by blocking the Na+/Cl- transporter at the distal convoluted tubule and thus help in lowering blood pressure. Both have the same effects on the body’s sodium, potassium and cholesterol levels.

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