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Everything You Need To Know About Erectile Dysfunction Drugs

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Fast Facts

  • PDE5 inhibitors are medications that are used to treat erectile dysfunction.
  • The drugs attach to an enzyme in the bloodstream and block it from breaking down a chemical compound that enables the blood vessels in the penis to dilate.
  • PDE5 inhibitors are also used to treat conditions including pulmonary hypertension and premature ejaculation.

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Sometimes, the best things in life happen by accident. The discovery of phosphodiesterase 5 inhibitors (PDE5) is one of those times. Researchers actually developed the common erectile dysfunction medication to treat chest pain, high blood pressure and heart problems. But when doctors started noticing their male patients requesting the medication by name to treat erectile dysfunction (ED), scientists knew something was up (pun intended).

If you’ve googled erectile dysfunction, chances are that your search has turned up PDE5 inhibitors. But you still might not be clear on what they are, how they work, and whether or not they can help treat any erection issues you might be having.

Here’s what you need to know about this class of erectile dysfunction medications to help you decide if PDE5 inhibitors might be right for you.

What are PDE5 Inhibitors?

Erectile dysfunction is the most common type of sexual dysfunction in men. ED—defined as the consistent or recurrent inability to acquire or sustain an erection of sufficient rigidity and duration for sexual intercourse or activity (1) —affects at least 12 million men in the U.S. alone. In other words, yes, it really does happen to every guy sometimes.

The Massachusetts Male Aging Study found that ED is increasingly common as men age: about 40 percent of men in their 40s and nearly 70 percent of men in their 70s suffer from ED. And a surprising 26 percent of men under 40 have erectile dysfunction. 

PDE5 inhibitors are a class of medications that are the mainstay of treatment for ED because they’re effective, easy to use, and come with few major side effects.

There are four different PDE5 inhibitors available today: tadalafil (sold under the brand name Cialis), sildenafil (Viagra), vardenafil (Levitra) and avanafil (Stendra).

Unlike over the counter (OTC) meds that claim to cure ED, PDE5 inhibitors can’t be purchased. You can only get them through a pharmacy using a prescription from your doctor.

Related: How to Talk to Your Doctor About ED

How Do PDE5 Inhibitors Work?

PDE5 inhibitors block the action of the enzyme phosphodiesterase type 5, or PDE5.

To better understand how PDE5 inhibitors work and how they can help treat ED, let’s first review how your body gets and sustains an erection.

When you’re sexually stimulated, nerve impulses in your body release neurotransmitters, or chemical messengers, into the corpora cavernosa, two spongy cylinders of tissue that forms the bulk of your penis. These chemical messengers tell the blood vessels in your penis to dilate, so that more blood can enter. As blood flows into the corpora cavernosa, they expand, making your penis firm and causing it to expand. 

Other fibrous tissue in the penis called the tunica albuginea traps the blood in the corpora cavernosa, sustaining the erection during sex.

Related: Why Can’t I Get and Keep an Erection?

The important link to all of this is cyclic guanosine monophosphate (cGMP), a chemical compound that enables the blood vessels in the penis—and other places in the body—to dilate. Cyclic GMP relaxes the smooth muscles inside the blood vessels of your penis and increases blood flow by 20 to 40 times.

PDE5 is an enzyme which binds to and breaks down cGMP, decreasing its effect. PDE5 inhibitors help with erectile dysfunction by attaching to PDE5 in the bloodstream, and block it from being able to contact and degrade cGMP. This allows cGMP to accumulate in the muscle, prolonging arterial dilation in the penis and thus, a prolonged erection.

It’s important to know that PDE5 inhibitors won’t cause you to get erections randomly. You need to be sexually stimulated for the drugs to work. But as many teen boys can attest, getting and sustaining an erection on demand is the best-case scenario.

erectile dysfunction medication Sildenafil
Could Low T Be Causing Your ED?

Hone’s test, which you can take from the privacy of your home, can analyze your testosterone levels.

Why PDE5s Can Help ED

A host of medical conditions can cause erectile dysfunction. Big culprits include diabetes, high blood pressure, and high cholesterol, heart disease, and vascular disease—all of which can decrease blood flow to the extremities, such as the penis.

But other factors are also to blame. Certain medications (prescription and non-Rx), smoking, drinking to excess, and not getting enough sleep or exercise are all linked to ED. Psychological factors can also play a role, including depression, stress, performance anxiety, and relationship issues.

When you talk to your doctor about ED, he or she should do a full workup to find out what’s preventing you from getting and keeping an erection, so that any underlying medical conditions can be identified, and if needed, treated.

PDE5 inhibitors are the first-line medical treatment for ED regardless of the cause. Keep in mind: these medications only treat ED. They can’t boost your libido, or make you more interested in having intercourse. However, ED is a common symptom in men with low testosterone. Testosterone replacement therapy (TRT) can help boost your sex drive, and studies show it can improve erectile function in males with mild ED.

If you’re concerned that you could have low testosterone, ordering Hone’s at-home test can tell you if your levels are in the normal range. If the test shows that your T level is low and ED is one of your symptoms, a Hone physician can help you determine the best treatment, which may include TRT and PDE5 inhibitors.

Erectile dysfunction is the most common type of sexual dysfunction in men.
  • Types of PDE5 Inhibitors

The first PDE5 inhibitors were discovered in 1990 and became available a few years later. Today, there are four FDA-approved PDE5 inhibitors: sildenafil, vardenafil, tadalafil, and avanafil.

The medications listed below are all effective and can be taken anywhere between 15 minutes to an hour before a sexual encounter, depending on the drug. In most cases PDE5 inhibitors should be taken on an empty stomach, so if your planned romantic interlude involves a steak dinner first, you may have to do some careful planning to get the timing right.

There are four PDE5 inhibitors currently approved by the FDA for treating ED:

Sildenafil

As the oldest PDE5 inhibitor on the market, sildenafil is also the most studied—there’s plenty of data from clinical studies regarding its safety. It’s also a popular choice because of its low cost.

  • Sold in generic and under the brand name Viagra
  • The first oral ED medication to be approved by the FDA in March of 1998, it has been used by millions in the decades since.
  • Also FDA-approved approved it for treating pulmonary arterial hypertension—a high blood pressure in the lungs that’s caused by blockage in their small arteries—when marketed under the brand name Revatio.
  • Prescribed in doses from 25-100mg.
  • Should be taken about an hour before sex.
  • Lasts about four hours.

Vardenafil

A PDE5 inhibitor sold under the brand names Staxyn and Levitra, vardenafil was approved by the FDA in August of 2003, and is also available as a generic.

  • Comes in a 10-mg oral disintegrating tablet.
  • Vardenafil’s chemical makeup may require smaller dosing to make you erect.
  • Your erections can last from four to eight hours (2).

Tadalafil

Sold under the brand name Cialis, tadalafil is known for having a longer duration of action than other PDE5 inhibitors.

  • Can provide relief from ED for 24-36 hours per dose.
  • Has been effective 72 hours after taking (3).
  • Standard dose: 10-20mg  at least one to two hours before intercourse.
  • Unlike some other ED meds, it doesn’t need to be taken on an empty stomach.
  • May also significantly boost your self-esteem and confidence (4). 
  • Also used to treat pulmonary arterial hypertension (5) and some studies indicate larger doses can also improve exercise capacity and duration. 
  • A lower daily dose has been shown to help with benign prostatic hypertrophy (BPH)—aka an enlarged prostate.

Avanafil

Sold under the brand name Stendra, avanafil is the newest option on the market. It was approved by the FDA for treating ED in 2012 and there isn’t a generic option available just yet.

Because there isn’t a generic option available yet, avanafil can be more expensive than other PDE5 inhibitors, and some studies suggest that it may not be as effective at lowering blood pressure.

  • Can start to provide relief from erectile dysfunction in as little as 15 minutes.
  • A good option for people whose sexual activity tends to be more spontaneous.
  • Less likely to cause certain side effects such as vision issues.

 

 

Risks and Side Effects

Like any medication, there are risks and side effects associated with PDE5 inhibitors. It’s important to discuss your individual medical history with your doctor before starting treatment. If you have a heart condition, you should also check with your cardiologist before taking PDE5 inhibitors.

Tell your doctor right away if you experience any side effects. The most common side effects of PDE5 inhibitors are headache, flushing, and dyspepsia (stomach upset). But clue him or her in if you experience any of these less common side effects:

Dangerously low blood pressure, especially in those with a history of a heart condition

  • Hearing loss or ringing in your ears
  • Dizziness
  • Altered color vision
  • Back pain
  • Nasal congestion
 

One of the best-known side effects of PDE5 inhibitors is priapism—an erection that lasts longer than four hours—though this is rare.

Who Shouldn’t Take PDE5 Inhibitors?

If you’ve experienced any of these conditions, make sure your doctor knows about them before you discuss using a PDE5 inhibitor, as the medication may not be right for you:

  • Low blood pressure
  • Uncontrolled high blood pressure
  • Heart failure
  • Angina
  • Heart attack within the past 90 days
  • Stroke within the last 6 months
  • Aortic stenosis
  • Penile deformities
  • Nitrate use or alpha blockers
  • Sickle Cell Disease
  • Multiple Myeloma
  • Leukemia

What Additional Conditions Are They Used to Treat?

In addition to treating ED, PDE5 inhibitors are prescribed for other conditions:

Pulmonary Hypertension (PH)

PH occurs when the blood pressure in the vessels of the lungs is elevated. PDE5 inhibitors help alleviate this condition by also dilating the arteries in the lungs, just as they do in the penis (6).

Premature Ejaculation (PE)

PDE5 inhibitors have been shown to relieve symptoms of PE when it is associated with ED. This works by keeping the contractile tissue of the penis and its accessory glands from contracting too soon, which would otherwise cause premature ejaculation (7).

Altitude Sickness

In some studies, sildenafil has been shown to reduce altitude sickness, particularly in people with pulmonary hypertension (8).

Penile Rehabilitation after Radical Prostatectomy

After a radical prostatectomy—surgical removal of the prostate gland and attached seminal vesicles—sildenafil has been found to improve regeneration of the nerve that causes erections, which can be damaged during surgery (9).

Natural Sources of PDE5 Inhibitors

There is some research investigating natural sources of PDE5 inhibitors, such as ginger, Paullinia cupana, muira puama and l- citrulline (10). However, the effects of these substances are being evaluated in animal studies and are not considered safe for human use. 

The FDA warns against supplements for treating ED because supplements are regulated and could contain harmful ingredients. The safety and effectiveness of these supplements also hasn’t been adequately studied. For now, stick to the FDA approved pharmaceuticals.

How Much Do They Cost?

Most PDE5 inhibitors can be found in generic forms and, if prescribed by your doctor, may be covered by your insurance.

The Bottom Line

PDE5 inhibitors are a safe, effective class of medications used to treat erectile dysfunction. If you are struggling to get or keep an erection, speak to a doctor. If you are prescribed a PDE5 inhibitor, take it according to the instructions on the label. 

References:
1. McVary KT (2007). Clinical practice. Erectile dysfunction. https://pubmed.ncbi.nlm.nih.gov/18077811/
2. Porst H, et al (2006). Extended duration of efficacy of vardenafil when taken 8 hours before intercourse: a randomized, double-blind, placebo-controlled study. https://pubmed.ncbi.nlm.nih.gov/16820261/
3. Evans, Jeffery D, and Stephen R Hill (2015). A comparison of the available phosphodiesterase-5 inhibitors in the treatment of erectile dysfunction: a focus on avanafil. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542406/
4.  Li JP, et al (2010). Efficacy of low-dose tadalafil on ED assessed by Self-Esteem and Relationship Questionnaire. https://pubmed.ncbi.nlm.nih.gov/21348208/
5. Henrie, Adam M et al (2015).Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636095/
6. Guazzi M, Samaja M (2007). The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development.  https://pubmed.ncbi.nlm.nih.gov/17691956/https://pubmed.ncbi.nlm.nih.gov/17691956/
7. Martyn-St James, Marrissa et al (2017). Phosphodiesterase Type 5 Inhibitors for Premature Ejaculation: A Systematic Review and Meta-analysis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503121/
8. Xu Y, et al (2014). Meta-analysis of clinical efficacy of sildenafil, a phosphodiesterase type-5 inhibitor on high altitude hypoxia and its complications. https://pubmed.ncbi.nlm.nih.gov/24673534/ 
9. Cohen DJ, Glina S (2015). Penile rehabilitation after radical prostatectomy. https://pubmed.ncbi.nlm.nih.gov/25642716/ 
10. Ferrini MG, et al (2018) Effect of ginger, Paullinia cupana, muira puama and l- citrulline, singly or in combination, on modulation of the inducible nitric oxide- NO-cGMP pathway in rat penile smooth muscle cells. https://pubmed.ncbi.nlm.nih.gov/29551532/ 

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