Viagra Australia
The most studied of these drugs is sildenafil (Viagra®). In several placebo controlled, randomized trials, this drug has been shown to improve erectile function. The pivotal study for sildenafil was published in 1998, which showed a clinically and statistically significant improvement in IIEF domain scores for men suffering from ED for greater than 5 years. The onset of action of sildenafil is approximately 20 min with a reported t ½ of 3–5 h and duration of action as long as 12 h. The important thing about sildenafil is that it should not be taken with a high fat meal because this will decrease the absorption of the medication.
Levitra
The FDA approved vardenafil (Levitra®) in 2003 after a study of 805 men with ED showed a clinically and statistically significant improvement in IIEF scores when compared to placebo. In this study, different doses were evaluated and men were categorized into mild, moderate, and severe ED. Approximately 40% of the moderate and severe ED men had improvement with the highest dose and over 79% of the mild ED men had improvement. Vardenafil is quickly absorbed with a Tmax of 45 min and a reported t ½ of 4–5 h. Onset of action has been recorded as early as 10 min. Just as in sildenafil, it is recommended that high at meals are avoided.
Cialis
Tadalafil (Cialis®) was approved at the same time as vardenafil and acquired the nickname “the weekend pill” because of the longer halflife than the other two drugs in its class. The Tmax of tadalafil is closer to 2 h and the t ½ is 17.5 h with a clinical efficacy reported of 12–36 h. Several studies showed the efficacy of tadalafil and the most important study involved 1,112 patients with mean duration of ED > 1 year. In this group, over 80% of the men had improved erections up to 36 h after administration of the drug. One other thing that differs from sildenafil and vardenafil is the absorption of tadalafil does not seem to be affected by high fat meals so there are no dietary restrictions.
The side effect profile for these drugs is very similar and is a result of the incomplete selectivity of PDE5 and the other sites that can be affected by inhibiting PDE5. PDE6 and PDE11 are the two most common families also affected by the drugs and contribute to the visual disturbances and myalgias, respectively. These side effects include headache, flushing, dyspepsia, and rhini tis. It has been shown with the continued use of vardenafil that these side effects are reduced significantly after the first few weeks. There is less than a 5% drop out rate secondary to side effects.
There are two things to warn your patients about with the use of PDE5 inhibitors. The first is that these drugs cannot be taken with nitrates. When sildenafil has been used, it is recommended to wait at least 24 h and when tadalafil has been used, 48 h is recommended. The results can be severe hypotension and all patients need to be aware of this contraindication. The second thing is patients need to be counseled to seek medical attention if they have any visual changes. Some visual changes can be mild and transient; however, there is a condition known as nonarteritic anterior ischemic optic neuropathy (NAION) that has been linked to the use of PDE5 inhibitors. This is independent of any effect on PDE6 found in the eye. It is an ischemic event to the optic nerve and is most likely seen in men with risk factors for diabetes, hypercholesterolemia, hypertension, and cardiovascular disease. This link was first made after a few cases were reported in a series of men using sildenafil. A review of all the available clinical trials with more than 13,000 men analyzed has shown no causation. Current recommendations are not to change prescription habits, but to advise patients to seek medical attention if they experience visual changes while taking a PDE5 inhibitor.
Initially there were concerns about the cardiovascular safety of these drugs. It is known that sildenafil can act as a mild vasodilator and there are warnings about orthostatic hypotension with concomitant use of ablockers. The use of PDE5 inhibitors is not contraindicated in men who are also on ablockers; they just need to be stabilized on this blood pressure medication prior to initiation of therapy. There were also concerns that use of PDE5 inhibitors would increase cardiovascular events. The safety of these drugs has been confirmed in several controlled trials with no increase in myocardial ischemic events or overall mortality compared to the general population. While there has been no increase of cardiovascular events associated with the use of these drugs, it is important to do a thorough cardiovascular history and exam prior to prescribing PDE5 inhibitors as the risk factors are shared for ED and cardiovascular disease.