The main classes of drugs that are preferred first-line agents for the initial treatment of high blood pressure (hypertension) in most patients include thiazide-type diuretics, calcium channel blockers (CCBs), ACE inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs). Clinical studies have shown that each of these four classes of medications is equally effective in reducing blood pressure. Furthermore, these agents have evidence of reducing cardiovascular risk in clinical trials.

Patients who fail to respond or respond poorly to initial treatment with first-line agents may benefit from higher doses or combinations of first-line agents. Alternative treatment options include beta blockers, alpha blockers, loop diuretics, aldosterone antagonists, peripherally acting adrenergic antagonists, alpha1/beta blockers, central alpha 2 adrenergic antagonists, and direct vasodilators.

Here is a review of medications used for treating high blood pressure. 

Thiazide diuretics

Thiazide diuretics work in the kidneys to increase the excretion of sodium, chloride, potassium, and water. They allow the body to remove excess water in the form of urine. The reduction in plasma volume causes a decrease in the resistance of blood flow that the heart has to pump against. 

The overall benefit of their use is a significant reduction in blood pressure. Thiazide diuretics decrease cardiovascular morbidity and mortality in placebo-controlled studies. In the Systolic Hypertension in the Elderly Program (SHEP), Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), and Medical Research Council (MRC) studies, thiazide diuretics reduced the risk of stroke, heart attacks, and the overall death rate associated with hypertension when compared to placebo.

Examples of thiazide and thiazide-type diuretics

• hydrochlorothiazide (HydroDiuril, Microzide)

• chlorothiazide (Diuril)

• chlorthalidone (Hygroton, Thalitone)

• indapamide (Lozol)

• metolazone (Zaroxolyn, Mykrox)

Chlorthalidone is the preferred thiazide-type diuretic with clinical evidence of reducing cardiovascular-related complications and death. The major evidence of chlorthalidone efficacy comes from the following studies:

In the ALLHAT trial, 41,000 patients were randomly treated with chlorthalidone, amlodipine, lisinopril, or doxazosin. Treatment with doxazosin was discontinued prematurely due to an increased risk of heart failure. In comparison to amlodipine and lisinopril, chlorthalidone treatment was associated with a significantly lower rate of heart failure. Also, chlorthalidone demonstrated a significantly lower rate of cardiovascular disease when compared to lisinopril.

An analysis of one clinical study comparing hydrochlorothiazide to chlorthalidone concluded that chlorthalidone treatment significantly reduced the risk of cardiovascular events and heart failure more than hydrochlorothiazide.

In the Multiple Risk Factor Intervention Trial (MRFIT), 2392 men were treated with chlorthalidone while 4049 men were treated with hydrochlorothiazide. Patients treated with chlorthalidone experienced less cardiovascular events (stroke, heart attacks, heart failure, chest pain, etc.). Additionally, systolic blood pressure and LDL cholesterol levels were also lower with chlorthalidone treatment. 

Side effects associated with thiazide diuretics include:

• dehydration

• electrolyte abnormalities (decrease in blood levels of potassium, sodium, and magnesium)

• increased blood glucose

• an increase in lipid levels

• increased uric acid levels

• an increase in calcium levels

• sexual dysfunction

• rash (sulfa allergy)

• photosensitivity

Drug Interactions associated with thiazide diuretics 

Lithium (Eskalith, Lithobid) — the clearance of lithium may be decreased during co-administration with thiazide diuretics. Lithium levels should be monitoring closely if these agents are given together.

Digoxin —  there is a risk of digoxin toxicity (high levels of digoxin) due to thiazide-related decreases in blood potassium and magnesium levels.

There is an increased risk for dangerous electrolyte disturbance when used with other diuretics or any medications that affect excretion of electrolytes.