Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. It refers to the inability to achieve or maintain an erection firm enough for sexual intercourse. While ED becomes more prevalent with age, it can occur at any age and lead to mental stress and relationship problems.

Phosphodiesterase type 5 (PDE5) inhibitors are the first-line oral treatment for ED and have revolutionized treatment since sildenafil (Viagra) was introduced in 1998. This comprehensive guide will cover everything you need to know about using PDE5 inhibitors to treat ED:

What are PDE5 Inhibitors?

PDE5 inhibitors are a class of drugs that work by relaxing the smooth muscle tissue in the penis to enhance blood flow. This makes it easier to get and maintain an erection when sexually aroused.

They inhibit the action of the PDE5 enzyme that breaks down cyclic guanosine monophosphate (cGMP). cGMP is a molecule that helps dilate blood vessels and increase blood flow. By inhibiting PDE5, these medications boost the nitric oxide (NO)-cGMP pathway important for erections.

There are currently four PDE5 inhibitors approved by the U.S. Food and Drug Administration (FDA) for treating ED:

  • Sildenafil (Viagra)
  • Tadalafil (Cialis)
  • Vardenafil (Levitra, Staxyn)
  • Avanafil (Stendra)

While they all work in a similar way, they have slight differences in how long they last and how quickly they start working.

How Do PDE5 Inhibitors Help With ED?

To understand how PDE5 inhibitors treat ED, it helps to understand the erection process. For an erection to occur, the brain sends signals to increase blood flow to the penis when aroused. Blood vessels dilate, more blood flows in, blood gets trapped by erectile tissues, and the penis becomes erect.

An erection requires:

  • Sexual stimulation to release NO
  • NO to activate the enzyme guanylyl cyclase
  • Guanylyl cyclase to produce cGMP
  • cGMP to relax smooth muscle cells and allow blood to fill the penis

PDE5 is responsible for breaking down cGMP. By inhibiting PDE5, more cGMP sticks around, blood vessels stay relaxed, and more blood can flow into the penis. PDE5 inhibitors enhance your natural erection response to sexual stimulation.

They do not cause erections on their own but require you to be sexually aroused. They also do not permanently cure ED but provide on-demand symptom relief.

Who Should Take PDE5 Inhibitors?

PDE5 inhibitors are commonly prescribed for men with:

  • Mild to moderate ED – they don’t work as well for more severe ED
  • Situational ED – occurs occasionally due to stress, anxiety, relationship problems, etc.
  • ED due to atherosclerosis – reduced blood flow to the penis
  • Nerve damage from diabetes, surgery, or injury that causes ED
  • High blood pressure, high cholesterol, obesity, metabolic syndrome
  • Prostate surgery or radiation therapy complications

PDE5 inhibitors are generally not recommended for men taking nitrate medications for heart conditions. Nitrates also lower blood pressure and combining them with PDE5 inhibitors could cause unsafe dips in blood pressure.

Those with severe liver or kidney disease may need dosage adjustments. PDE5 inhibitors are not approved for use in women or children under 18 years old.

Choosing a PDE5 Inhibitor

The four PDE5 inhibitors have many similarities but differ in onset of action, duration of effects, and side effects.

Sildenafil is the generic name for Viagra. It starts working in about 30-60 minutes and lasts around 4-6 hours.

Tadalafil is the active ingredient in Cialis. It kicks in within 30 minutes and can work for up to 36 hours, earning it the nickname “the weekend pill.”

Vardenafil goes by the brand names Levitra and Staxyn. It takes effect in 30-60 minutes and generally lasts 4-6 hours.

Avanafil is sold as Stendra. It’s the newest PDE5 inhibitor and starts working in 15-30 minutes with effects lasting 6-12 hours.

There’s no definitive evidence showing one PDE5 inhibitor works better than the others. Response varies between individuals. Most men end up finding one that provides optimal results for their needs.

Talk to your doctor about trying different medications and doses to find your best option. Consider the duration of action and onset time that works for your lifestyle.

How to Take PDE5 Inhibitors

PDE5 inhibitors come in varying doses and pill strengths. Starting doses are often lower and can be adjusted based on response and side effects.

Here are some general dosing guidelines:

  • Sildenafil: 25-100 mg taken 1 hour before sex
  • Tadalafil: 10-20 mg taken 30 minutes before sex
  • Vardenafil: 5-20 mg taken 1 hour before sex
  • Avanafil: 50-200 mg taken 15-30 minutes before sex

Some important points about using PDE5 inhibitors:

  • Take them on an empty stomach for faster absorption
  • Effects may last longer after a high fat meal
  • Don’t exceed the maximum recommended dose
  • Wait 24 hours between doses of sildenafil or vardenafil
  • Don’t take them daily unless advised by your doctor
  • Plan sexual activity around when the medication is most potent
  • Be patient for multiple attempts to see full effects

Also talk to your doctor about medication interactions and safety. Don’t use PDE5 inhibitors with nitrates or “poppers” containing amyl nitrite.

Side Effects of PDE5 Inhibitors

PDE5 inhibitors are generally safe and well tolerated by most men. Common side effects (affecting 1-10% of users) include:

  • Headache
  • Facial flushing
  • Indigestion
  • Nasal congestion
  • Back pain
  • Muscle aches
  • Nausea
  • Dizziness
  • Rash

Rare but serious side effects include:

  • Priapism – prolonged erection lasting over 4 hours
  • Hearing or vision loss
  • Irregular heartbeat

Seek medical attention if you experience serious side effects. Back pain and muscle aches are more common with tadalafil. Vision issues are more likely with sildenafil and vardenafil.

Overall, PDE5 inhibitor side effects are usually mild and tend to improve over time with continued use. Starting with lower doses can minimize side effects.

Efficacy of PDE5 Inhibitors

Clinical trials have found PDE5 inhibitors effective for most men with ED. About 50-80% of men experience improved erections and sexual performance.

However, they don’t work immediately. It may take 6-8 attempts to see full effects. Be patient and use them properly for optimal results.

Factors that can influence efficacy include:

  • Age – lower response rates with advanced age
  • Baseline ED severity – worse ED means poorer results
  • Cause of ED – better response for vascular-related ED
  • Dose strength – higher doses equal better effects
  • Medication interactions – some drugs reduce PDE5 inhibitor effects
  • Overall health – chronic health conditions may reduce effects

Response also varies individually. If you don’t get results with one PDE5 inhibitor, trying a different one may be helpful. Combining them with other ED treatments also improves efficacy.

How Much Do PDE5 Inhibitors Cost?

The cost of PDE5 inhibitors depends on:

  • Brand vs. generic – brand name Rx are more expensive
  • Dosage strength – higher strength pills cost more
  • Quantity – costs per pill drop with higher quantities
  • Insurance coverage – prescription co-pays lower costs

Here are some average costs in the U.S. for brand name pills:

  • Viagra 100mg: $65 per pill
  • Cialis 20mg: $75 per pill
  • Levitra 20mg: $60 per pill
  • Stendra 200mg: $75 per pill

Generic sildenafil and tadalafil are significantly cheaper, usually under $1 per pill. With insurance coverage, prescription co-pays can lower costs to $10-25 per pill. Shopping around pharmacies can help find the best pricing.

There are also licensed generic versions of Viagra and Cialis available overseas at much lower costs. Their quality and safety standards may not be as stringent. Discuss purchasing international generics with your doctor.

PDE5 Inhibitor Alternatives

Some alternatives if PDE5 inhibitors don’t work for you include:

Other ED Medications

  • Alprostadil – injectable/insertable drug that improves blood flow
  • Papaverine – injectable drug that relaxes penile blood vessels
  • Phentolamine – injectable medicine also for blood vessel relaxation

While effective, injections and inserts may be uncomfortable for some men. Topical and urethral alprostadil are also options.

Natural Supplements

  • L-arginine – amino acid that may enhance nitric oxide
  • DHEA – testosterone precursor hormone
  • Yohimbine – alkaloid that acts as a stimulant
  • Panax ginseng – adaptogenic herb with vasodilating properties

Herbal supplements have modest effects compared to ED drugs for most men. Quality, safety, and long-term effects require further study.

Lifestyle Changes

  • Quit smoking
  • Exercise regularly
  • Lose excess weight
  • Reduce alcohol intake
  • Treat chronic health conditions
  • Relieve stress and anxiety
  • Get good quality sleep

Healthy lifestyle improvements combined with PDE5 inhibitors can enhance arousal, erections, and sexual performance.

Penis Pumps and Extenders

Vacuum erection devices and traction penis extenders can serve as non-drug alternatives for some men. They mechanically draw blood into the penis or apply tension to enlarge it over months of use.

Results vary widely and penis pumps must be used each time before sex. Small penis size or curvature may also be helped by extenders.

Counseling and Psychotherapy

For cases of ED predominantly due to mental or emotional causes, counseling and psychotherapy may help. They can manage issues like stress, anxiety, depression, and relationship conflicts contributing to ED.

Using PDE5 Inhibitors Safely and Effectively

To maximize results from PDE5 inhibitors, consider these tips:

  • Take them correctly at effective doses and times
  • Try different PDE5 inhibitors if one doesn’t work
  • Give them multiple attempts to see full effects
  • Make healthy lifestyle improvements too
  • Manage medical conditions contributing to ED
  • Be patient and keep expectations realistic
  • Open up communication and foreplay with your partner
  • Don’t rely on pills alone for sex – focus on pleasure
  • Seek counseling for mental or emotional issues

Avoid unsafe practices like combining PDE5 inhibitors with nitrates or amyl nitrite. Seek immediate medical help for priapism or sudden vision or hearing changes.

The Bottom Line

PDE5 inhibitors represent a major breakthrough in ED treatment thanks to their ease of use, good safety record, and proven effectiveness for most men. They don’t work instantly or permanently cure ED. However, they reliably produce erections on demand to regain sexual spontaneity and enjoyment.

Choosing a PDE5 inhibitor depends on factors like duration of action, cost, and personal response. Sildenafil and tadalafil are popular first-line options. Trying different medications and proper use can improve results. Combining PDE5 inhibitors with other treatments and healthy lifestyle changes may further optimize your sexual health.

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