Analysis of the antihypertensive advantages and adverse reactions of thiazide diuretics

What are the advantages and adverse reactions of thiazide diuretics in lowering blood pressure?

Multiple large-scale clinical trials have shown that thiazide diuretics can significantly reduce mortality, stroke, and cardiovascular events in patients, have good safety profiles, and are inexpensive. Therefore, both the Chinese and European hypertension guidelines recommend them as the initial and maintenance medication for antihypertensive treatment.

Diuretics are particularly beneficial for elderly patients with hypertension and heart failure. They can be used in combination with ACEIs or ARBs and calcium channel blockers. Low-dose thiazide diuretics have little effect on glucose and lipid metabolism. High-dose diuretics may have some impact on serum potassium, uric acid, and glucose metabolism; regular monitoring of serum potassium, blood glucose, and uric acid is necessary. Gout is a contraindication for their use.

(1) Characteristics of diuretics in treating hypertension:

①Thiazide diuretics have a slow onset of action, a long duration of action, and a mild effect. Their antihypertensive effect often takes effect after several weeks, and their effect is maximized at low doses. Restricting sodium intake helps to maximize their effectiveness. ② The efficacy of this class of drugs is positively correlated with age; that is, the older the patient, the better the efficacy.

③ When used in combination with other antihypertensive drugs, the efficacy of this class of drugs can be significantly increased. Especially when used with ACEIs/ARBs, not only is the antihypertensive effect significantly enhanced, but there is also a complementary effect on the clinical characteristics of both.

④ From a pharmacoeconomic perspective, diuretics have the best efficacy/cost ratio.

⑤ Potassium-sparing diuretics have a very weak antihypertensive effect, so they are rarely used alone. They are often used in combination with thiazide or loop diuretics to prevent hypokalemia.

(2) The best indication for thiazide diuretics in treating hypertension: Because diuretics mainly work by reducing blood volume, and have played a good role in preventing and treating heart failure, myocardial infarction, and stroke in multiple large-scale clinical trials, they have a significant advantage in treating hypertension complicated with heart failure, elderly patients with isolated systolic hypertension, patients at high risk of recurrence after stroke, and patients with high risk of coronary heart disease, making them the best indication for treatment. The ALLHAT trial results showed that chlorthalidone was superior to amlodipine (Norvasc) in reducing heart failure and lowering systolic blood pressure; it was also superior to lisinopril in lowering blood pressure, reducing cardiovascular events, and preventing stroke and heart failure. Many meta-analyses and trials have reached similar conclusions. Therefore, although diuretics are inexpensive and have many adverse reactions, their effects on lowering blood pressure and preventing cardiovascular complications have not been surpassed by many newly developed drugs. Guidelines in the US JNC-7, Europe, WHO-ISH, China, and other countries and regions have listed low-dose diuretics as the first-line drugs. They can be used alone or in combination with other drugs.

(3) Major adverse reactions that may occur with diuretics: The antihypertensive effect of diuretics is undeniable, but if used improperly, especially at excessive doses, adverse reactions may occur. ① Hypokalemia: Thiazide diuretics cause sodium and potassium excretion. When used alone at a large dose (50-100 mg) of hydrochlorothiazide, the incidence of hypokalemia (<3.5 mmol/L) can reach 20%. With a smaller dose (12.5-25 mg/day), the incidence is only about 5%. In a hypokalemic state, the antihypertensive effect is significantly reduced; therefore, potassium supplementation or the addition of potassium-sparing diuretics should be timely.

② Hyperglycemia: There seems to be an increase in new-onset diabetes among people using diuretics. Some analysts suggest this may be due to hypokalemia inducing hyperglycemia.

③ Elevated uric acid and blood lipids: Diuretic treatment may lead to abnormalities in uric acid and blood lipids.

Therefore, during diuretic use, blood electrolytes, blood lipids, blood glucose, creatinine, and blood urea nitrogen should be monitored regularly.

How to effectively utilize the advantages of diuretics while minimizing their adverse reactions?

The antihypertensive effect of thiazide diuretics is undeniable. However, in some individuals, hypokalemia and adverse effects on blood sugar and lipids limit their use. If the dosage is carefully controlled (low doses, such as less than 25mg daily for hydrochlorothiazide), and blood potassium, lipids, blood sugar, and uric acid levels are regularly monitored, and medication is avoided in situations where certain adverse reactions are likely (such as diarrhea or inability to eat normally), their use is generally safe. If necessary, potassium-sparing diuretics such as spironolactone or triamterene can be taken concurrently.