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Oral Treatment For Erectile Dysfunction

Home | Oral Treatment for Erectile Dysfunction

Cialis, Levitra and Viagra: How do these drugs work?

Cialis (Tadalafil), Levitra (Vardenafil) and Viagra™ (Sildenafil) work by selectively inhibiting an enzyme in the penis called Phosphodiesterase V (PDE V), a chemical that takes away the erection. By blocking PDE V temporarily, these medications empower the chemical, Nitric Oxide (NO) that occurs naturally with arousal to initiate, produce and maintain an erection. Patients need sexual stimulation and foreplay to release NO initiate an erection in order for these medications to be effective. They are called phosphodiesterase inhibitors.

This class of medication is a safe and effective oral treatment for men with erectile dysfunction of physical, psychological or mixed cause. However, it is important that patients should be aware of the low probability (less than 50%) that intercourse will be possible after the first dose - particularly in severe or advanced cases and especially when using Viagra or Levitra. The majority of men who stop Viagra because of apparent lack of effect will in fact respond and achieve intercourse if they continue to try again, progress from 50 mg to 100 mg, or take the pill without food on an empty stomach (3 hours after eating). Taking Viagra or Levitra on a full stomach will not only reduce their peak concentration in the body by 30 to 50% but in addition will delay their peak concentration by one hour. In other words one may have to wait after intake before initiating sexual activity. Cialis peak concentration and time before reaching maximum absorption is not affected by a full stomach. Because of this it remains my drug of choice for the treatment of ED and I always prescribe it first. In addition many of my patients experience fewer side effects with Cialis then with the other two. Finally Cialis has a long period of activity and patients are successful at intercourse up to 36 hours after taking this pill. This represents a distinct advantage from the patient’s perspective as it diminishes the need for planning. Sex can be more spontaneous and natural. Planning kills the mood. Having sex long after taking the pill makes men feel more normal! For these reasons I will first try Cialis on all my Patients and reserve Viagra and Levitra for those men who do not tolerate Cialis.

The steps illustrated in Table 1 will help optimize the chances of success of Levitra and Viagra.

Reliable safety data gathered in the 10 years since these PDE % inhitors were launched confirm that side effects such as Priapism (prolonged erection), red eyes, painful eyes, syncope(fainting), tachycardia (rapid heart rate), and nausea do occur, but are rare. Back pain and muscle aches occur rarely with Cialis. HIV medications (protease inhibitors) have been shown to raise their blood levels. Certain patient groups are more susceptible to a decrease of their blood pressure, including those with aortic stenosis, hypertrophic obstructive cardiomyopathy, and multiple system atrophy. Finally, all PDE 5 inhibitors remain contraindicated in patients taking nitrates.

A few new safety concerns such as visual and hearing loss have emerged in the past year, however these remain extremely rare reinforcing that these medications are very safe. Indeed, we now know that many patients with cardiovascular disease (CVD) and ED benefit from it.
 

The following can be prescribed a PDE 5 inhibitor (Cialis, Levitra, Viagra) safely without the need for extensive Cardiovascular  investigation²:

  • men who are a symptomatic and have fewer than three  risk factors for coronary artery disease
  • those with controlled hypertension
  • those with mild stable angina
  • patients who have undergone successful coronary revascularisation (bypass or stent placement)
  • men with a history of uncomplicated  heart attack that happened  greater than 6-8 weeks ago
  • those with mild valvular disease of the heart
  • patients with mild left ventricular disease and congestive heart failure (NYHA Class I)
 
Alternative oral therapies for Erectile Dysfunction (availability may vary geographically) are Uprima (apomorphine), and phentolamine. Both Uprima and phentolamine have very low or no efficacies and therefore for present purposes will not be addressed. 

Uprima is approved for the treatment of Erectile Dysfunction in Europe and initial sales have not been very impressive (less than 20% of ED market). Refill rates are dismal supporting lack of efficacy. 

Phentolamine’s application to the FDA was withdrawn and the drug is not available.  

Although Viagra, Levitra and Cialis differ in their biochemical potency and selectivity, and in onset and duration of action, it is important not to extrapolate those findings inappropriately to the clinical setting. For example, greater biochemical potency does not necessarily translate into enhanced clinical efficacy. The same is true of selectivity. In short, there appears to be little biochemical or clinical differences between the three agents except for the lack of food interaction and the duration of activity for Cialis. All three medications are contraindicated in patients who take nitrates.

A recent survey looking at what patients with ED really want from their treatment found that efficacy and a favorable side-effect profile were the highest priorities³ Fast onset was desirable, but there were major differences in what was considered fast. Duration was important only in terms of lasting long enough to complete intercourse. Few men (or their partners) felt that multiple erections, or the ability to achieve them over time, were critical as long as one dose was enough for a successful encounter. Most complaints were about high cost or lack of insurance coverage.

An underlying desire was reported by most couples for initiation of sex to be normal (spontaneous and natural). Few patients fully understood the duration of activity that Viagra can provide, and its advantages. Cialis may indeed fulfill the desire that couples and patients with ED have for the initiation of sex to be normal (spontaneous and natural). Although Viagra, Levitra and Cialis are safe and effective they do, like all medications, have disadvantages. They essentially enhance partial (sexual) erections, rather than initiating them. At best, the response rate among men with advanced ED (for example following radical prostatectomy) is 30%. Fewer than 505 of men with Diabetes will respond. Correct administration of Viagra and Levitra is critical, and if one does not work when taken correctly, no other oral “Viagra like drug” (PDE5 inhibitor like Levitra or Cialis) will either.

In conclusion, the potencies of Viagra, Levitra and Cialis are broadly similar, but each has unique pharmacological properties related to its molecular structure. Viagra is an exemplary PDE-5 inhibitor that, after 10 years of widespread clinical use, is acknowledged to be effective and particularly well tolerated. Cialis and Levitra are the newer medications and are similar to Viagra in their efficacy and contraindications. The only new attributes of clinical significance are the lack of food interaction and the long duration of action of Cialis. This may translate into greater efficacy of the first dose as well as a return to more spontaneous (normal) initiation of sexual activity (broader window of opportunity).  
 

Discussion

Q. Is it possible to identify potential non-responders to oral therapy?
Dr. Eid. No, it is not possible to identify potential non-responders to a PDE 5 inhibitor such as Cialis, Levitra or Viagra, other than by a trial of these medications in the setting of sexual activity. Patients, who appear to be non-responders to Viagra or Levitra, need to repeat a trial on an empty stomach a few different times before giving up. Cialis absorption and onset of action is not affected by food. The 20-30% who still do not respond generally have ED related to an irreversible physical abnormality due to chronic poor blood flow (often smoking-related) or damaged penile tissue (often diabetes, high cholesterol and after prostate cancer surgery). The best option for these patients remains an inflatable penile prosthesis.
Q. You said that the PDE5 inhibitors were comparable in efficacy. What about reports that Levitra is more effective than Viagra in treating ED among men with diabetes?
Dr. Eid. Clinical trial reveals that all three medications have the same success regardless of patient age, underlying medical condition or severity of erectile dysfunction. There is no head-to-head evidence of that, and what literature there is may be misleading. My belief is that clinical experience will show them to be similar.

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References

1. McCullough AR, et al. J Urol 2001. In press.
2. DeBusk R, et al. Am J Cardiol 2000; 86: 175-81.
3. Data from Six Degrees Survey, October 2001.

Table 1. Optimizing Viagra and Levitra therapy:
  • men who require fast onset or better absorption should avoid fatty meals or take these pills on an empty stomach;
  • maximize sexual stimulation and arousal;
  • start foreplay later in older patients (who may need up to 2 hours to absorb the medicicne);
  • consider partner issues;
  • do not give up before making at least 3 attempts at intercourse having at the maximum dose: Viagra 100 mg, Levitra 20mg.
 

More on Cialis, Levitra and Viagra

Cialis (Tadalafil)
Oral medications such as Cialis, Levitra and Viagra are available for the treatment of erectile Dysfunction. They are in a class called PDE 5 inhibitors. They work to restore a normal system of blood flow in the penis so that an erection can occur with sexual stimulation.
Highlights of Cialis:
  • Only ED medicine clinically proven to work up to 36 hours.
  • Works as fast as 30 minutes in some men.
  • Gives you the freedom to choose the moment that is right for you.
Side Effects:
The most common side effects include headache, upset stomach, back pain and muscle aches. The side effects usually go away after a few hours. In the rare event of Priapism seek immediate medical help to avoid long term injury. Another uncommon side effect reported was a sudden decrease or loss of vision.
Who should not take Cialis:
Cialis is contraindicated in patients using nitrates. If you use recreational drugs called “poppers” like amyl nitrate and buty nitrite do not take Cialis. If Cialis is taken with certain Alpha Blockers, it can result in a sudden drop of blood pressure, which could lead to dizziness or faintness. It can however be used with Flomax 0.4mg.

Tell your doctor if you take any other medications including prescription and non-prescription medicines, vitamins or any health supplements as Cialis and these may affect each other adversely.
How to use Cialis:
Cialis is available by prescription only. It is taken orally before sexual activity, not more than once daily. It may be taken with or without food. In some patients, the dose strength and maximum frequency of use may be adjusted.
 

Levitra (Vardenafil)

Levitra is also an FDA approved medication for the treatment of Erectile Dysfunction.
How Levitra works:
Levitra is an oral medicine, available by prescription only, and should be taken approximately 60 minutes prior to sexual activity. It should be taken no more than once daily. It can be taken with or without food.
Side effects:
The side effects are generally mild and do not last very long. The most common side effects are headache, flushing, stuffy or runny nose. In rare cases Priapism and vision changes have been observed.
Contraindications:
Levitra is contraindicated in patients who take any form of medication known as nitrates or recreational drugs called “poppers” like amyl nitra or butyl nitrate. If you are taking any alpha blockers, Levitra is not the right medication for you.
 

Viagra™

Highlights of Viagra™
  • First effective FDA-approved oral medication for the treatment erectile dysfunction
  • Boosts natural process of erection during arousal
  • Works across broad range of Erectile Dysfunction causes
  • Over 6 million patients have tried it
  • Approximately 250,000 doctors have prescribed it
  • Over 14 million prescriptions written
  • Over 100 million tablets dispensed
  • Unlike placebo-like drugs, Viagra™ has high refill rate
How to Use Viagra™
If taken on an empty stomach, it takes about 85 minutes for Viagra™ to be absorbed into the circulation and reach the penis. Some patients (younger men) may experience benefits from the medication as early as 30 minutes after taking it. A high fat meal will delay the absorption of Viagra™, and therefore it is recommended that Viagra™ is taken on an empty stomach or after a lowfat meal. Furthermore, once absorbed, Viagra™ will stay in the circulation for approximately four to six hours, which represents the window of sexual opportunity. If initially not successful, patients should try Viagra™ at 100mg on 3 different occasions before concluding that the medication is ineffective.
Viagra™ Efficacy
Viagra™ is effective in two-thirds of men with erectile dysfunction regardless of age and the severity of Erectile Dysfunction However, certain groups of men using the drug do better than others. For example, spinal cord injured males have better results than patients suffering from cardiovascular disease (e.g. hypertension, high serum fat levels), and patients who have undergone treatment for prostate cancer treatment (e.g. removal of the prostate or radiation therapy) seem to benefit the least.
Viagra™ Side Effects
Most side effects are mild and well-tolerated. The following are the most common reported side effects: headache, flushing of the face, heartburn, and nasal congestion. A small percentage (3%) of people may develop visual disturbance; it may take the form of a blue haze or tinge as well as increased perception of brightness. This effect is very mild, transient, and reversible.
Who Should Not Take Viagra™
Viagra™ is CONTRAINDICATED for patients who take any medications that contain nitrates. This includes patients who need nitrates (including nitroglycerine) on an intermittent basis for the treatment of angina.

In patients used to regular exertion, sexual activity poses no special cardiovascular risk. Even in patients who have a history of myocardial infarction (MI), there is little risk of MI during intercourse for those who exercise regularly. However, there is insufficient information on the cardiovascular risk in previously sexually inactive men who become sexually active. Stress test and/or referral to a cardiologist may be appropriate, and variables such as patient's age, medical history and existing medical conditions may be relevant.