Understanding the Pharmacotherapy of Hypertensive Disorders

The Importance of Managing Hypertension

Managing hypertension is critical for improving patient health and mitigating the associated risks. Beyond minimizing patient risks, a comprehensive understanding of hypertension management is crucial for enhancing national and global health. The Centers for Disease Control and Prevention (CDC) notes that approximately 48.1% of adults have hypertension; however, less than 25% of hypertensive patients effectively manage their chronic disease.

Uncontrolled hypertension increases the risk of heart disease and stroke, leading causes of death in the United States. The CDC estimates that hypertension contributed to nearly 700,000 deaths in the US in 2021.

Beyond heart attack and stroke, the American Heart Association (AHA) notes that uncontrolled hypertension can contribute to kidney disease or failure, vision loss, sexual dysfunction, angina, peripheral artery disease (PAD), and high cholesterol.

Hypertension Management Strategies

Despite the rate of uncontrolled hypertension, healthcare professionals and patients have many tools at their fingertips to manage these conditions.

The first line of defense to manage hypertension includes lifestyle changes. The World Health Organization (WHO) notes that eating a healthy, low-salt diet, like the Mediterranean diet, can help lower blood pressure. Other lifestyle changes, including maintaining a healthy weight, engaging in physical activity, and quitting tobacco, have effectively reduced blood pressure.

However, some patients cannot control their hypertension through lifestyle changes alone, turning to medications as a management tool.

A guide from the CDC highlights four general principles for prescribing antihypertensives. The first principle reveals that most patients will require two or more medications to manage hypertension and reach their target blood pressure. However, the second and third principles identify contraindications between drug classes. The CDC notes that most patients should not be given two drugs in the same category. Additionally, patients should not take ACE inhibitors with ARBs. The final principle maintains that providers should increase the dose of the initial agent to the most tolerable intensity before adding a second medication to their treatment regimen.

According to the CDC guide, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and diuretics are typically the first in-line medications for managing hypertension.

Diuretics

Diuretics reduce blood pressure by triggering the kidneys to excrete sodium and water, reducing fluid volume, widening blood vessels, and, in turn, reducing blood pressure.

The AHA identifies four categories of diuretics used to manage hypertension: thiazide diuretics, potassium-sparing diuretics, loop diuretics, and combination diuretics. Thiazide diuretics, including chlorthalidone, hydrochlorothiazide, indapamide, and metolazone, are the most common according to Georgetown University’s Department of Medicine.

As one of the earliest antihypertensives, diuretics are well understood, making them easier to manage. For example, the most common side effects resulting from a depletion of mineral potassium include weakness, leg cramps, and fatigue. Other potential side effects include gout and sexual dysfunction.

Often, this class of medications is used in combination with other antihypertensives.

ACE Inhibitors

Angiotensin-converting enzyme inhibitors reduce blood pressure by blocking the production of angiotensin II, a hormonal compound that narrows the blood vessels and increases blood pressure.

This class of drugs includes benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. According to Georgetown University, these drugs are some of the most commonly prescribed medications for hypertension, as they are effective and have a favorable side effect profile.

The drugs do not alter daily functions, including concentration, sleep, exercise abilities, sexual performance, and overall well-being. However, like any drug, these medications come with some side effects.

For example, approximately 10–20% of patients taking these medications have a persistent dry cough that can be reversed when the drug is discontinued. Patients who experience this symptom are often taken off all ACE inhibitors as the side effects are associated with the entire class of medications.

UpToDate notes some less common side effects, including dry mouth, nausea, rash, muscle pain, kidney dysfunction, and elevated blood potassium, may occur. In less than 1% of people, 0.1–0.7%, ACE inhibitors cause angioedema, causing the lips, tongue, and throat to swell.

ARBs

Angiotensin receptor blockers, like ACE inhibitors, effectively block the renin–angiotensin system (RAS). Instead of stopping the production of angiotensin, these medications block the receptors that respond to angiotensin II.

This class of medications includes candesartan, eprosartan, irbesartan, sartan, olmesartan, telmisartan, and valsartan.

Unlike ACE inhibitors, ARBs do not cause a cough or angioedema; however, some side effects include dizziness, kidney damage, low potassium, and really low blood pressure.

Both ACE inhibitors and ARBs are not recommended for pregnant individuals as they can injure or kill a developing fetus.

Calcium Channel Blockers

Calcium channel blockers, like amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, and verapamil, reduce calcium entry into blood vessels. Since calcium is required for contraction, calcium channel blockers cause blood vessels to dilate, reducing blood pressure.

Common side effects of calcium channel blockers include headache, nausea, swollen ankles, and constipation.

The following medications are also utilized as pharmacotherapeutic options for patients with hypertension when the first-line drugs are ineffective:

• Calcium channel blockers
• Beta-blockers
• Vasodilators
• Alpha-blockers
• Direct renin inhibitors
• Aldosterone agonists

Despite the abundance of available medications for managing hypertension, many patients with hypertension do not have it under control. An article published in Hypertension revealed that, between 2015 and 2018, 38.0% of hypertensive patients did not know they had hypertension. Only 46.4% of patients knew they had hypertension and were being treated with medications, leaving 15.6% aware of and untreated for the condition.

“To increase BP control, interventions to increase hypertension awareness should be directed toward younger adults, those without a healthcare visit in the past year and without CVD risk factors. Interventions are also needed to increase BP control among US adults already taking antihypertensive medication, potentially through greater use of single-pill combinations, especially among older adults, non-Hispanic Black and Hispanic adults, and those without a usual source of healthcare,” concluded researchers in the publication.