The five most commonly prescribed classes of blood pressure medication are ACE inhibitors, ARBs, calcium channel blockers, thiazide diuretics, and beta-blockers. The 2025 guidelines from the American Heart Association and American College of Cardiology endorse four of these (thiazide diuretics, calcium channel blockers, ACE inhibitors, and ARBs) as first-line treatments based on strong trial evidence for lowering blood pressure, preventing cardiovascular disease, and being well tolerated. Beta-blockers, while widely prescribed, are now typically reserved for people who have a specific reason to take them, such as a history of heart attack or heart failure.
Here’s what each medication does, what taking it feels like day to day, and how your doctor decides which one fits your situation.
ACE Inhibitors: Lisinopril and Similar Drugs
ACE inhibitors work by blocking your body from producing a hormone called angiotensin II, which narrows blood vessels. Without it, your blood vessels relax and widen, reducing the pressure your heart has to pump against. Lisinopril is the most commonly prescribed drug in this class. It’s typically started at 10 mg once daily, with most people landing somewhere between 10 and 40 mg.
The most distinctive side effect is a persistent dry cough, which affects a significant minority of people and is the number one reason patients switch to a different class. Other common effects include dizziness, fatigue, and headache. If you develop swelling in your face, lips, or tongue, that’s a rare but serious allergic reaction that requires immediate medical attention.
ACE inhibitors are a preferred choice if you have diabetes or chronic kidney disease, because they help protect the kidneys beyond just lowering blood pressure. One important interaction to know: common pain relievers like ibuprofen and naproxen (NSAIDs) can blunt the blood-pressure-lowering effect of ACE inhibitors, so you may need an alternative for pain management.
ARBs: Losartan and Related Medications
ARBs target the same hormonal system as ACE inhibitors but work at a different step. Instead of blocking the production of angiotensin II, they block the receptors where that hormone attaches to blood vessel walls. The practical result is the same: blood vessels relax, and pressure drops. Losartan is the best-known drug in this class, usually started at 25 to 50 mg once daily with a maximum of 100 mg.
The big advantage of ARBs over ACE inhibitors is that they rarely cause the nagging cough. If you tried an ACE inhibitor and couldn’t tolerate it, an ARB is the usual next step. Side effects are generally mild. Like ACE inhibitors, ARBs are preferred for people with kidney disease or diabetes, and they carry the same caution about potassium levels rising. You should not take an ACE inhibitor and an ARB together, as the combination increases risk without added benefit for most people.
Calcium Channel Blockers: Amlodipine
Calcium channel blockers prevent calcium from entering the muscle cells in your blood vessel walls. Without that calcium signal, the vessels can’t squeeze as tightly, so they stay more relaxed. Amlodipine is the most widely used drug in this class, started at 5 mg once daily with a maximum of 10 mg. Its long duration of action means once-a-day dosing works well, and missing a dose by a few hours doesn’t cause a dramatic rebound in pressure.
Ankle swelling is the hallmark side effect, caused by fluid shifting into the lower legs as blood vessels dilate. It’s not dangerous, but it can be bothersome enough that some people switch medications. Other common effects include flushing (a warm feeling in the face), headache, and drowsiness. Calcium channel blockers are a good option for people with diabetes and are often chosen for patients who can’t take ACE inhibitors or ARBs.
One notable interaction: grapefruit juice can increase blood levels of certain calcium channel blockers by interfering with how the liver processes them, potentially intensifying side effects. Amlodipine is less affected than some others in the class, but it’s worth mentioning to your pharmacist if you regularly drink grapefruit juice. These drugs can also alter the way your body clears digoxin, a heart medication, so combining them requires careful monitoring.
Thiazide Diuretics: Hydrochlorothiazide
Thiazide diuretics lower blood pressure by helping your kidneys flush out extra sodium and water. Less fluid in your bloodstream means less pressure on your artery walls. Hydrochlorothiazide (often shortened to HCTZ) is the most recognized name in this class, typically started at just 12.5 mg daily. Most people stay at 12.5 to 25 mg, and higher doses add more side effects without much additional blood pressure benefit.
Because you’re losing extra fluid, increased urination is expected, especially in the first few weeks. Taking the pill in the morning rather than at night helps avoid disrupted sleep. The more important concern is that thiazides can lower your potassium levels over time, which can cause muscle cramps, weakness, or irregular heartbeat. Routine blood work to check potassium and kidney function is standard while you’re on this medication. Some people take a small potassium supplement or eat more potassium-rich foods like bananas and sweet potatoes to compensate.
NSAIDs (ibuprofen, naproxen) can reduce the effectiveness of diuretics, just as they do with ACE inhibitors. Thiazide diuretics are included in the treatment options for people with diabetes, though your provider will keep an eye on blood sugar, since thiazides can modestly raise glucose levels.
Beta-Blockers: Metoprolol
Beta-blockers slow your heart rate and reduce the force of each heartbeat by blocking the effects of adrenaline on the heart. This lowers both your heart rate and the amount of blood your heart pumps per beat, which together bring down blood pressure. Metoprolol is the most commonly prescribed beta-blocker, available in an immediate-release form (typically 50 to 100 mg twice daily) and a sustained-release form (100 to 200 mg once daily).
Fatigue is the side effect people notice most. Your body is used to running at a certain speed, and beta-blockers deliberately slow things down. Dizziness, lightheadedness, upset stomach, and constipation or diarrhea are also common. One important rule: never stop a beta-blocker abruptly. Sudden withdrawal can cause a rebound spike in heart rate and blood pressure that can be dangerous. Your doctor will taper the dose gradually if you need to stop.
While the 2025 guidelines don’t list beta-blockers as first-line for uncomplicated high blood pressure, they remain essential for people with heart failure, a prior heart attack, or certain heart rhythm problems. They interact significantly with some calcium channel blockers (specifically verapamil and diltiazem), and combining them can slow the heart too much. NSAIDs also weaken the blood-pressure-lowering effect of beta-blockers.
How Your Doctor Chooses Between Them
For stage 1 hypertension (systolic pressure between 130 and 139, or diastolic between 80 and 89), guidelines recommend starting with a single medication from one of the four first-line classes and adjusting from there. The choice often comes down to your other health conditions. Kidney disease or diabetes points toward an ACE inhibitor or ARB. A history of heart problems may favor a beta-blocker or ACE inhibitor.
Stage 2 hypertension (140/90 or higher) is a different picture. Current guidelines recommend starting with two medications from different classes, ideally combined into a single pill. Common pairings include an ACE inhibitor with a calcium channel blocker, or an ARB with a thiazide diuretic. The single-pill approach isn’t just convenient: research consistently shows people are more likely to take one pill daily than two, and faster blood pressure control reduces the window of risk.
Race and ethnicity also factor into the decision. The guidelines specifically note that Black adults may respond better to calcium channel blockers or thiazide diuretics as initial therapy compared to ACE inhibitors or ARBs alone, though combination therapy often bridges that gap.
Interactions That Apply Across Classes
A few interactions cut across nearly all blood pressure medications. NSAIDs, the most common over-the-counter pain relievers, can weaken the effect of beta-blockers, diuretics, and ACE inhibitors by interfering with how the kidneys handle sodium. If you take a blood pressure medication and need regular pain relief, acetaminophen is generally a safer choice, though it’s worth discussing with your pharmacist.
Liver metabolism matters too. Many blood pressure drugs, including calcium channel blockers, certain beta-blockers, and some ACE inhibitors, are broken down by the same liver enzyme system. Medications like cimetidine (an older heartburn drug) can slow that breakdown and effectively increase blood pressure drug levels, while seizure medications like phenytoin can speed it up and reduce effectiveness. Any time a new medication is added to your regimen, a quick interaction check with your pharmacist is a practical safeguard.