Mr G’s ED Treatment
Oral Phosphodiesterase Inhibitors
Treatment must be tailored to the individual. Some men may not desire treatment at all. Others, perhaps like Mr G, are interested primarily in gathering information about treatment options before initiating therapy.
The oral phosphodiesterase inhibitors — , , and — represent first-line therapy for men with ED. and have similar pharmacokinetic properties, with peak serum concentrations at approximately 1 hour and a half-life of 4 to 5 hours. has a considerably longer half-life of approximately 18 hours, with evidence that erectile function continues to be enhanced for at least 36 hours. Although to date no head-to-head clinical trial results between these drugs have been published, their overall clinical efficacy appears to be fairly similar, with minor differences in results likely due to variations in the patient populations studied. For example, in a double-blind randomized study of 532 men, successful intercourse was achieved in 69% of men receiving 100 mg of compared with 22% of men receiving placebo. In a study of 348 men using (20 mg), 59% successfully reported intercourse at 36 hours, compared with 28% in the placebo group. And in a multicenter, double-blind, placebo-controlled trial, 69% of men receiving (20 mg) successfully reported completing intercourse, compared with 22% receiving placebo.
Approximately half of men with diabetes mellitus or more advanced coronary and peripheral vascular disease report benefit. A success rate of roughly 30% has been noted following radical prostatectomy. An attempt at treatment with oral agents is warranted only if the nerves have been spared, and even then, success is unlikely unless at least partial return of erections has occurred.
Patient education is critical for optimal response to . This includes informing the patient to take the medication on an empty stomach and to time sexual activity so that it occurs within 1 to 6 hours, as well as explaining that sexual activity of some sort is necessary to obtain a positive effect. If an initial starting dose of 50 mg is ineffective, I recommend increasing the dosage immediately to 100 mg: nothing is gained by repeated attempts at a subtherapeutic dose. Similar instructions should be provided for . However, instructions regarding the timing of intercourse may be considerably liberalized for due to its prolonged duration of effect, although peak concentration occurs somewhat later, at 2 hours.
Limitations. Many men who fill prescriptions for never refill them, and many others, like Mr G, receive a prescription but never fill it. Reasons for this include ambivalence about taking a medication for sex, cost, concerns regarding risk, and negative partner attitudes regarding sex or the medication. Many men and their partners believe that sexual activity should be natural and spontaneous, and they object to the planning required for successful use of oral medications. Still others may hope that their own sexual abilities will return with time or with resolution of personal problems.
Risks. The phosphodiesterase inhibitors have undergone extensive clinical study and have a fairly benign safety profile when taken as directed. The single important contraindication is the use of any nitrates, either on a chronic or intermittent basis, due to the potential for significant hypotension. also should not be taken within 4 hours of 
-adrenergic blockers, and should not be used at all with them. The most common adverse effects are headache (15%), flushing (10%), nasal/sinus congestion (8%), dyspepsia (7%), and transient color vision changes (3%). Mr G should be reassured that priapism is extremely rare and treatable, and that he may safely take in combination with his antihypertensive medications, atenolol and hydrochlorothiazide.
Cardiovascular Effects. The relationship of PDE 5 inhibitors and cardiovascular health has been extensively studied. Daily administration of (20 mg) for 26 weeks in healthy men or patients with mild ED resulted in blood pressure changes similar to those observed after placebo administration. studies have revealed a minor reduction in systolic and diastolic pressures of 2 to 8 mm Hg without appreciable change in heart rate.
The cardiac effects of during exercise in men with suspected coronary artery disease was studied in a randomized, double-blind, crossover study of 105 men with ED who underwent supine bicycle echocardiograms 1 hour after taking or placebo. No negative effect of was seen with regard to symptoms, exercise duration, or ischemia. Similar safety was noted in a double-blind single-dose crossover study using (10 mg) or placebo in 41 men with stable exertional angina who underwent exercise tolerance testing. No differences were noted between and placebo with regard to exercise time or time to first awareness of angina, but did significantly prolong the time to ischemic threshold.
A persistent concern among men and their partners is that or its competitors might cause a myocardial infarction, based on early reports of sudden death reported in the lay press. An unquantified number of these anecdotal cases were clearly related to the contraindicated simultaneous use of nitrates. Nevertheless, the data regarding PDE 5 inhibitors and coronary artery disease have been reassuring. Cardiac catheterization for severe coronary artery disease was performed in 14 men before and 45 minutes following administration of (100 mg), resulting in no negative hemodynamic effects. Moreover, an investigation of reports of -associated deaths showed no difference from expected death rates, and the rate of cardiac events in England among users of appeared to be no higher than that of the general population. Nevertheless, it must be recognized that sexual activity itself is associated with a small risk of myocardial infarction, and cardiovascular assessment should be considered prior to treatment of ED in any patient considered at increased risk for a cardiac event.
Since cardiovascular disease often coexists with ED, the Princeton Consensus Panel was convened to review existing data and provide recommendations regarding the treatment of sexual dysfunction in men with heart disease. Those recommendations indicate the need for no additional evaluation prior to treatment for men in a low-risk group, including those with controlled hypertension; mild, stable angina; history of uncomplicated myocardial infarction; and mild valvular disease. A high-risk group was identified in whom treatment of sexual dysfunction should be withheld until further safety data could be accumulated. This group included men with unstable or refractory angina, uncontrolled hypertension, high-grade congestive heart failure, myocardial infarction within the previous 2 weeks, high-risk arrhythmias, obstructive cardiomyopathy, and moderate to severe valvular disease. Men with intermediate risk, eg, those with moderate angina or recent myocardial infarction (<6 weeks), should undergo further cardiac evaluation before restratification into one of the other groups.
Other Treatment Options for ED
Penile injections with vasoactive medications are effective in 70% to 80% of patients, have an onset of action within 10 minutes, and are nearly painless. They represent the most common treatment for men who take nitrates or have had no success with phosphodiesterase inhibitors and are used by approximately 10% of men with ED. Alprostadil is most frequently prescribed but can cause an unpleasant burning sensation in about 20% of men. Papaverine and phentolamine can be used to avoid this problem or used in combination with alprostadil for greater efficacy. In a study of 615 cases of men using penile injection therapy, penile fibrosis was noted in 3%, and 4% of men experienced a prolonged erection, representing 0.3% of injections. Although less than half of men taught to use penile injection therapy continue to use this therapy for more than a few years, satisfaction rates among users are comparable to men who use as therapy for ED.