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Cardiac-wise Cialis has the shortest QTc interval and may in fact be the safest to use for cardiac patients although all three drugs are extremely safe. None of them have a QTc interval of greater of 10 milliseconds, which would have caused the drug to fail FDA clearance. The long half-life of approximately 20 hours is not unusual in today's modern health. Most drugs given by general practitioners to their patients have half-lives even greater than 20 hours and there is no concern about side effect profiles. If side effects occur with Cialis, they are usually short duration, mild, and occur within the first 24 hours.

Another concern about Cialis is the fact that it has the greatest affect on the PDE-11 enzyme system, which is found in many organs including the heart, muscle, and testicle. Concerns about fertility have been diminished with several studies of six-months duration/two sperm cycles in which there appears to be no quantitative or qualitative abnormalities in the semen analysis. Longer studies or experiences may be necessary to determine whether or not this drug does in fact have negative effects on fertility in men. In addition, muscle aches and pains particularly in the low back and gluteal area are more common with Cialis (7%) versus Levitra or Viagra (less than 1%). Younger, more muscular and more physically active men, particularly when confined or not physically active for a period of time, get this discomfort, which seems to be related to PDE-5 inhibitors in general and muscular vascular congestion. Physical activity makes the pain disappear and in addition when taking multiple Cialis tablets in time the discomfort disappears.

One interesting study involved PDE-11 knockout rats in which the genetic material to make PDE-11 has been destroyed and the generations of rats that form have no PDE-11 activity. There was found to be no fertility, muscle pathology, or cardiac pathology in these rats indicating that PDE-11 inhibition even though unknown appears not to be detrimental.

Having discussed the basic information about Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil) let us look at the ideal circumstances for using these drugs.

Cialis with its long half-life and relatively long duration of action of 36 to 100 hours appears to be the easiest, most cost effective, spontaneous, and natural of the three drugs. Two or three pills per week may be all that is necessary for function without concern for time and spontaneity.

On the other hand, having the ability to maximize nocturnal erections by using two pills per week of Cialis is extremely advantageous since it maximizes nocturnal blood flow during the three to five erections that every male gets at night, oxygenates the penis, decreases the chances of fibrosis and scarring, and in the process prevents irreversible penile damage and irreversible untreatable erectile dysfunction. As we gain experience, it is possible that the treatment of choice will be to combine Cialis with one of the shorter-acting drugs. A booster of Levitra or Viagra prior to sexual activity after taking Cialis on Tuesday and Friday may be the ideal choice for many patients who do not get an optimal response to 20 mg of Cialis every 36 hours. Lastly, if sexual activity occurs more than twice per week Cialis becomes more cost effective and becomes the drug of choice.

For those patients who have hard-to-treat erectile dysfunction, Levitra may be the drug of choice because of its relatively high potency and effectiveness in these types of patients. Many think of Levitra as a more potent Viagra, however, Levitra has a much longer duration of action and in many men a 20 mg Levitra tablet will be effective with stimulation up to 20 or 24 hours. Levitra tends to work very rapidly with 25% of the patients getting an optimal response within 16 minutes of taking the drug. Certain individuals, such as single men who cannot plan their sexual activity until the last minute, may find Levitra to be their drug of choice.

Viagra has certainly maintained itself over time as the safest "gold standard" of PDE-5 inhibitors. We are really not able to compare Viagra to Levitra and Cialis because the studies on Viagra used improvement in sexual function rather than penetration or sexual satisfaction as their endpoint and therefore the efficacy statistics may be higher than they should be.

On the other hand, Levitra and Cialis used penetration and sexual satisfaction as their endpoint, but disqualified those patients who did not respond to Viagra; therefore their efficacy figures may in fact be higher than they should be. Both inequalities may actually cancel each other out and many feel from an efficacy point of view that the three drugs are fairly close in their ability to produce satisfactory and optimal erections for sexual activity.

Viagra has the longest safety record and profile of just about any drug approved by the FDA. However, Levitra and Cialis have equally safe profiles for a shorter period of time. The overall side effect profile percentages for all three drugs are approximately the same with the exception that there are no eye manifestations or flushing with Cialis and minimal eye manifestations with Levitra. However, there is some question as to whether or not Levitra and Cialis have a milder degree of side effects including headache, stomach upset, and nasal congestion. Cialis rarely causes nasal congestion.

Older men who have less frequent sex and who are happy with the responses using Viagra should certainly continue Viagra. Some patients who do not get optimal responses to Cialis may find that Viagra is more to their liking. In general, all three drugs work and the patients should talk to their doctors about finding the one that works best for them and their sexual lifestyle. (August 2004)

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