Alpha-blockers

Overview

What are alpha-blockers?

Alpha-blockers are medications that treat high blood pressure. They can also treat some conditions affecting the circulatory system, prostate, and help with treating certain types of tumors. They work by slowing down specific types of cell activity in your nervous system.

How do they work?

Alpha-blockers work by partially blocking the way some cells in your body receive instructions. They do this by blocking alpha-receptors, which are found on cells in specific areas or organs in your body. Those receptors tell their cells when to squeeze, constrict or tighten. By blocking those receptors, those cells stay relaxed. Because many of those cells line your blood vessels — controlling how wide or narrow those vessels are — keeping them relaxed lowers your blood pressure.

More about alpha-receptors

Your nervous system works by transmitting chemical and electrical signals throughout your body. That chemical communication works very similarly to a lock-and-key system. The chemical signals — also known as neurotransmitters — are the keys. They can travel through your bloodstream to various locations in your body. Receptors are the locks, allowing chemicals to attach and activate the cells.

Some of those receptors found throughout your body are called adrenergic receptors (or sometimes adrenoceptors). They got their name because a chemical your body makes, adrenaline (also called epinephrine), acts as a master key and can activate all adrenergic receptors.

Adrenergic receptors, including alpha-receptors (sometimes identified using the Greek letter α for alpha), come in multiple types and sub-types.

How medications use alpha-receptors

If a chemical has the right structure, it can attach to a receptor. Chemicals that can attach to a receptor are either agonists or antagonists:

• Agonists: These chemicals attach to a receptor and “unlock” it, activating the cell and telling it to take a certain action. They can be chemical signals made by your body, or they can come from medications you take.
• Antagonists: These chemicals can attach to receptor sites but can’t unlock and activate them. Antagonists hold onto the receptor site and prevent their activation. The effect is similar to putting a key into a lock that isn’t quite the right fit. It can go into the lock but can’t open it. Blocking enough receptors on enough cells slows down those cells’ activity.

What do alpha-receptors control?

Alpha-receptors come in two different subtypes, with the subtypes having some overlap but also controlling different functions.

Alpha-1 (A1) receptors

Locations and functions of these receptors include:

• Smooth muscle. This type of muscle forms linings of your blood vessels, which is how they help regulate blood pressure. A1 receptors cause your blood vessels to constrict and cause an increase in your blood pressure.
• Eyes. A1 receptors cause the pupils in your eyes to get smaller, which helps you see in brighter conditions.
• Skin. A1 receptors control the muscles that cause your hair to stand up. This is what causes you to have goosebumps when you feel cold.
• Urinary tract. These receptors are how you control your bladder muscles. They’re also found in the prostate.

Alpha-2 receptors

These receptors are mostly found in the following locations:

• Smooth muscle. The smooth muscle that lines your blood vessels also has A2 receptors in addition to A1 receptors. That’s why A2 receptors also play a role in blood pressure.
• Nervous system. This includes your brain, spinal cord and nerves. A2 receptors in the nervous system help manage your neurotransmitter levels. This is especially true of norepinephrine (also called noradrenaline), a neurotransmitter that works alongside adrenaline.
• Blood. A2 receptors can activate platelet cells in your blood, causing them to clot and bunch together. Platelets are key in your body’s natural response to an injury, helping seal and repair wounds.
• Pancreas. A2 receptors in the beta cells of your pancreas slow and prevent the release of insulin into your body.
• Fat cells. Activating A2 receptors in fat cells stops them from breaking down for use as an energy source.

Are there different types of alpha-blockers?

Some alpha-blockers will target only certain alpha-receptors. This characteristic is “selectivity,” and it is a part of the decision process when choosing an alpha-blocker to treat a condition. Alpha-blockers can be non-selective or selective for A1 receptors. There are — for now — no approved selective alpha-2 blockers.

The following alpha-blockers are currently approved and in use in the United States:

What conditions are treated by alpha-blockers?

Just like the name suggests, alpha-blockers are alpha-receptor antagonists. They attach to alpha-receptors and keep them activating certain cells.

Alpha-blockers have approval from the U.S. Food and Drug Administration to treat the following conditions:

High blood pressure (hypertension)

Alpha-blockers treat high blood pressure by stopping A1 and A2 receptors from activating. Blocking that activation relaxes blood vessels, lowering blood pressure.

Approved alpha-blockers for high blood pressure include:

• Doxazosin.
• Prazosin.
• Terazosin.

Benign prostatic hyperplasia (BPH)

Benign prostatic hyperplasia (also known as benign prostatic enlargement) is a condition that causes the prostate gland to enlarge. When this happens, it can make it hard to urinate (pee) because the prostate presses on the urethra. It can also cause urine to remain in your bladder, causing bladder stones and infections. Over time, it can also lead to kidney failure. Alpha-blockers can cause your prostate muscle to relax, making it easier for urine to pass through.

Approved alpha-blockers for BPH are:

Prostate gland-selective (these have fewer systemic side effects than non-selective)

• Alfuzosin.
• Doxazosin.
• Silodosin.
• Tamsulosin (this is non-selective for the prostate gland).
• Terazosin.

Pheochromocytomas and paragangliomas

These are the same type of tumor but have different names depending on their location. They can be cancerous (malignant) or non-cancerous (benign). These tumors can — but don’t always — create extra adrenaline and norepinephrine. When you have too much of either in your body, it’s like you’re having an overdose on them, with symptoms to match. Those symptoms include headache, sweating, heart problems and more. Alpha-blockers keep the excess neurotransmitters from having an overdose-like effect.

• Pheochromocytomas (fee-oh-crow-mo-sigh-toe-ma): These form on your adrenal glands, located at the top of your kidneys.
• Paragangliomas (para-gang-lee-oh-mas): These are tumors that often grow near the carotid artery in your neck, but can also form around nerves elsewhere in your body.

The following drugs have approval for treating pheochromocytomas and paragangliomas:

• Phentolamine (can also help diagnose these tumors).
• Phenoxybenzamine.

Skin and soft tissue treatments

Phentolamine can prevent damage to areas of skin caused by norepinephrine leaking out of your blood vessels and into the surrounding tissue. It can also reverse the effects of some local anesthetics.

Off-label uses

Alpha-blockers can also treat certain conditions even when not specifically approved by the FDA for those conditions. This is known as “off-label” prescribing. It’s often done when there's evidence a medication can treat a condition, and the benefits outweigh the potential risks. Off-label prescribing is legal, medically acceptable and ethical when done safely and responsibly.

Alpha-blockers are commonly used off-label for the following conditions:

• Prazosin: This can treat nightmares and sleep disruptions caused by post-traumatic stress disorder (PTSD) and treatment of circulation issues caused by Raynaud’s phenomenon.
• Tamsulosin: This can treat chronic prostatitis (prostate inflammation) and chronic pelvic pain syndrome in men, as well as lower urinary tract symptoms in men. It can also help with passing kidney stones and treat symptoms caused by ureteral stents (scaffold-like devices that hold your urethra open, keeping them from being blocked by kidney stones or bladder stones).
• Alfuzosin, doxazosin, terazosin and silodosin: These four alpha-blockers see off-label use to treat kidney stones that have become stuck in the ureters, the tubes that run from your kidneys to your bladder.

Are alpha-blockers commonly prescribed?

Alpha-blockers are very commonly prescribed for certain conditions. In 2019, more than 5.4 million people with Medicare Part D coverage — about 11% of all Medicare Part D beneficiaries — were prescribed an alpha-blocker.