A friend complained to Huazi, saying that he had to use a combination of four antihypertensive drugs, including diazepam, lolpheniramine, sartan and diuretics, to barely control his blood pressure to the standard. If his blood pressure rises again in the future, what other drugs can he use?

Hua Zi said that if three antihypertensive drugs, including thiazide diuretics, cannot control blood pressure, or four antihypertensive drugs are used to control blood pressure, this type of blood pressure is called refractory hypertension. You can try to use aldosterone antagonists in combination, which have different targets from traditional antihypertensive drugs.

1. Exclude pseudo-refractory hypertension

For refractory hypertension that cannot be controlled even with multiple drugs, it is important to distinguish true from false . Some people have high blood pressure values ​​because of incorrect blood pressure measurement methods, inaccurate blood pressure monitors, or "white coat hypertension". It is recommended to use 24-hour dynamic blood pressure monitoring to obtain the true blood pressure situation.

Long-term use of glucocorticoids, contraceptives, traditional Chinese medicine containing licorice, erythropoietin, non-steroidal anti-inflammatory drugs, etc. may lead to high blood pressure and reduce the effect of antihypertensive drugs.

There are also secondary factors , such as kidney disease, renal vascular disease, primary aldosteronism, pheochromocytoma, Cushing's syndrome and other diseases, which can cause secondary hypertension. If the primary disease is not effectively treated, blood pressure is often difficult to control.

2. Aldosterone antagonists that can lower blood pressure

Aldosterone is a mineralocorticoid hormone secreted by the adrenal glands that can activate the mineralocorticoid receptor (MR). In disease states, excessive activation of MR will lead to increased potassium excretion, water and sodium retention, increased blood pressure, and subsequent target organ damage through multiple pathways such as the central nervous system, kidneys, and blood vessels.

Antagonizing the effects of aldosterone can lower blood pressure . Spironolactone is a traditional drug used to antagonize aldosterone, but its receptor selectivity is poor. While lowering blood pressure, it also binds to sex hormone receptors, causing breast development in men, sexual dysfunction, and menstrual disorders in women when taken.

Another commonly used drug is eplerenone , which has been on the market overseas for more than 20 years, will be available in China in 2023, and will be included in the medical insurance catalog at the end of 2024. Eplerenone's antagonism to aldosterone receptors is lower than that of spironolactone, but its receptor selectivity is higher than that of spironolactone, so its antihypertensive effect is similar to that of spironolactone, but its adverse reactions are much lower.

Finerenone is also an aldosterone antagonist and has also been included in the medical insurance catalog. Eplerenone and finerenone are similar drugs with different structures. Finerenone has a higher selectivity for MR in the kidney, so it is now mainly used to treat chronic kidney disease related to diabetes.

3. What should you pay attention to when taking medicine?

1. Pay attention to electrolytes : The use of aldosterone antagonists will increase blood potassium, so renal function and blood potassium need to be checked before taking the medicine. The medicine can only be used when the glomerular filtration rate (eGFR) is ≥45ml and the blood potassium is <5.0mmol/L ; some patients may experience hyponatremia, so during the medication period, the electrolyte level should be checked regularly.

2. Long time to take effect : This type of drug usually needs to be taken for 2 to 4 weeks to achieve the best blood pressure lowering effect. So if the effect is not obvious or blood pressure fluctuates in the early stage of medication, don't worry too much.

3. Impact on male hormones : Even if eplerenone, which has milder adverse reactions, is used, some people may still experience androgen antagonism, and some male patients may experience sexual dysfunction.

4. Other adverse reactions : Nausea, diarrhea, abdominal pain and other digestive tract irritation may occur. Some patients may have dry cough, but it is usually mild and does not affect the use of the drug. However, if allergic reactions such as rash and urticaria occur, the drug should be discontinued and medical treatment should be sought.

In summary, when treating refractory hypertension, aldosterone antagonists can be used in combination under the guidance of a doctor. The targets of these drugs are different from those of traditional antihypertensive drugs. When taking these drugs, we should pay attention to the effects on blood potassium and beware of hyperkalemia.

If you have any questions about medication, please consult a doctor or pharmacist. I am pharmacist Huazi, welcome to follow me and share more health knowledge.