Additional Medications for Treating High Blood Pressure

If blood pressure cannot be controlled despite multiple combination treatments (triple combination) or if side effects force stopping medications, current guidelines recommend adding a mineralocorticoid receptor antagonist or a different diuretic, or adding an alpha-blocker or a beta-blocker (these can also be considered earlier in treatment if the indication fits).

Alpha blockers

These drugs mainly act on alpha-1 receptors and block the effects of adrenaline and noradrenaline there. Alpha-1 receptors are mainly found on smooth muscle cells, including in blood vessels and the urinary tract. They cause blood vessels to widen and thus lower blood pressure. They are also prescribed for benign prostate enlargement.

Some beta-blockers also have additional alpha-blocking effects, for example carvedilol.

Side effects:

Doxazosin is frequently associated with respiratory and urinary tract infections. Symptoms such as headache, a fast heartbeat and palpitations, as well as stomach and intestinal complaints, are also observed while taking it.

For other side effects, please refer to the manufacturer's package leaflet.

Active ingredients: Doxazosin (Doxacor, Doxagamma etc.), Urapidil (Ebrantil, Urapidil)

Renin inhibitors

Wirkungsweise Renin-Hemmer zur Blutdrucksenkung

Renin inhibitors: How they work

A renin inhibitor acts relatively early in the reninangiotensinaldosterone system. It already blocks the conversion of angiotensinogen to angiotensin I by the enzyme renin.

Renin inhibitors: Side effects

Few side effects have been observed, and they occur relatively rarely.

However, after the early termination of the ALTITUDE study due to interim results, the manufacturer Novartis informed in 2012 about new recommendations for prescribing aliskiren. According to these, aliskiren-containing medicines should not be prescribed in combination with ACE inhibitors or angiotensin receptor blockers. For patients with diabetes mellitus or impaired kidney function, combining aliskiren with ACE inhibitors or angiotensin receptor blockers is contraindicated.

Renin inhibitors: Drugs/Products

The active substance aliskiren is marketed under the following product names:

Rasilez, Rasilez HCT (no longer produced for the German market)

The combination drug Rasilamo (which combined aliskiren with a calcium antagonist) was withdrawn from the market due to insufficient benefit.

Endothelin receptor antagonists (ERAs)

Endothelin receptor antagonists are another class of drugs for treating resistant high blood pressure. However, most preparations are only approved for treating pulmonary arterial hypertension. Only aprocitentan received EU approval in 2024 for the treatment of resistant hypertension.

An endothelin receptor antagonist blocks endothelin from binding to its receptors (ETA and ETB), which reduces endothelin's vasoconstrictive effect. This relaxes the blood vessels and lowers blood pressure.

Endothelin receptor antagonists: Side effects

As with most medications, endothelin receptor antagonists can have side effects. The most common are headaches, edema (fluid accumulation), and dizziness. It is important that patients are regularly monitored by their doctor so side effects can be detected and treated early.

Sources

This article comes from BloodPressureDB – the leading app since 2011 that helps hundreds of thousands monitor their blood pressure every day. Our content is based on carefully researched, evidence-based data and is continuously updated (as of 12/2025).

Author Sabine Croci is a qualified medical assistant with many years of experience in internal medicine and cardiology practices as well as in outpatient care, and has led BloodPressureDB's specialist editorial team since 2015. Thanks to her extensive additional qualifications as a paramedic, first responder and in various therapy and emergency areas, she provides solid, practical and reliably reviewed information.

We hope you found the article helpful. For good blood pressure control, it's important to take your medications correctly. Our app BloodPressureDB will gladly remind you when to take them. It also keeps track of your medication supply and notifies you in time when you're running low. This feature is fully available in the free version as well. Get the free app now.