Blood Pressure-Lowering Medications

The renin-angiotensin-aldosterone system is a hormonal system that controls blood pressure in healthy people. In people with diabetes, hypertension, heart disease, heart failure, and kidney diseases, inhibition of the RAAS system have been well documented to reduce risks for cardiovascular events and kidney failure. There are 2 main classes of RAAS blockers: the ACE inhibitors (e.g. perindopril, enalapril, lisinopril, and ramipril) and angiotensin receptor blockers (e.g. losartan, telmisartan, irbesartan, valsartan and candesartan). The both work similarly at lowering blood pressure and have similar side effects, except for cough and rarely angioedema in people taking ACE inhibitors. Most guidelines recommend starting treatment with ACE inhibitors as the first line given their cheaper cost and similar efficacy as compared to angiotensin receptor blockers. 

Side effects of RAAS blockers include high potassium levels and initial worsening of kidney function. In most people, this initial worsening of kidney function is often followed by a stable phase. Studies have shown that people with initial worsening of kidney function with RAAS blockers actually get greater benefits in terms of kidney protection.

RAAS blockers should not be taken by pregnant women. The decision to take or not to take RAAS blockers during childbearing age should be discussed with the diabetes care providers.

Dihydropyridine calcium-channel blockers, such as amlodipine, felodipine, nifedipine, and lercandipine, are another group of medications that have been shown to reduce cardiovascular risks in people with diabetes and hypertension. 

Calcium channel blockers are generally safe. Side effects of calcium channel blockers include mild leg swelling, which may improve with dose reduction or combined treatment with a RAAS blocker.

Thiazide diuretics work by removing excess salt into the urine. They include hydrochlorothiazide and indapamide. Thiazide diuretics have been shown to have comparable effects and cardiovascular benefits as compared to RAAS blockers and calcium channel blockers in people with diabetes and hypertension. Thiazide diuretics also work synergistically with other blood pressure-lowering medications, hence they are often combined together as fixed-dose combination tablets. The combined effects of thiazide diuretics and other blood pressure-lowering medications is especially useful in people with resistant hypertension.

Side effects of thiazide include low serum sodium level (hyponatremia) and serum potassium level (hyp0kalemia). These side effects can be precipitated or become worse during intercurrent illness or dehydration. Hypokalemia due to thiazide diuretics can be treated with potassium supplements, while hyponatremia due to thiazide diuretics can be a recurring problem and may require replacing thiazide diuretics with other medications. 

Other blood pressure-lowering medications used in people with diabetes and hypertension include beta blockers, alpha blockers, mineralocorticoid receptor antagonists, and medications that work on the central nervous system. These medications are used as additional treatments for blood pressure-lowering if blood pressure is still not controlled with RAAS blockers, calcium channel blockers, and thiazide diuretics.