Pharmacologic Agents
Pharmacologic treatment using vasoactive agents is now coming to the forefront as one of the most effective means of treating impotence. These agents, directly administered into the corpora cavernosum, mimic the vascular phenomenon of erection, eliciting a response within 5–10 minutes that lasts 30 minutes to one hour.
The dose of the drug varies depending on the cause of the impotence, therefore a careful evaluation should be obtained before instituting treatment. Patients with arterial insufficiency, neurological or psychological erectile dysfunction generally respond to lower doses than those with veno-occlusive disease. It is important that both the patient and his partner be included in discussion and instruction regarding erectile dysfunction treatment.
Papaverine, phentolamine and alprostadil are currently used in practice. Papaverine, a smooth muscle relaxant, results in vasodilation; and alprostadil, a synthetic prostaglandin E1, relaxes the corporal smooth muscle leading to engorgement of the corpus cavernosum. Phentolamine, an a-blocker, opposes arterial constriction, increasing arterial inflow.
Adverse effects of these drugs include priapism, fibrosis, penile pain and hematoma at the injection site. Papaverine carries a higher incidence of priapism than alprostadil (4% vs. 2.6%) but alprostadil has a higher rate of penile pain (41% vs. 12.5%).Fibrosis in the cavernosum occurs more frequently with papaverine than alprostadil (25.4% vs. 7.8%), however, it has been suggested that fibrosis may be prevented by careful injection technique and 3–5 minutes of compression at the injection site.
These agents work synergistically and allow a smaller dose of each agent to be used, thereby decreasing side effects.Informed consent needs to be obtained since these drug combinations are not FDA approved specifically for treatment of impotence. Alprostadil, available as Caverject, is the only agent with FDA marketing approval to treat erectile dysfunction. It is packaged as a 10 or 20 mg disposable kit containing a syringe, lyophilized powder and diluent the patient mixes before injecting. Caverject is convenient but costly, approximately $17 for the 10 mcg dose and $22 for the 20 mcg dose, for each single-use kit.
Two formulations commonly used are 1) alprostadil with phentolamine and 2) alprostadil, phentolamine and papaverine combined (Table 3). Our clinic experience is that the three-drug combination produces a better erection in erectile dysfunction of vascular origin than the two-drug mixture. However, the latter is preferred in patients with purely neurogenic or psychologic erectile dysfunction, which requires much smaller doses. The patient and his partner are educated on the causes of erectile dysfunction, informed how the medication works and told of potential side effects. They are given instruction on injection technique and what to do in case of an adverse event.
After signing an informed consent, the patient undergoes an in-office titration beginning with a dose of 0.01 to 0.03 mL (using a 1/2“ 29-gauge 1/2 cc insulin syringe, which corresponds to 1–3 units). The patient or his partner is instructed on injection technique and performs the titration dosing under supervision. Injections are given on the side of the shaft of the penis, in the first one-half area closest to the body, taking care to avoid visible blood vessels and alternating sides with each injection. Following injection, pressure is applied to the injection site for five minutes.
This minimizes the chance of hematoma formation and may decrease fibrosis. If the response is partial, an additional 0.01 to 0.03 mL is given after approximately 15 minutes. A maximum of two doses per visit is given until a satisfactory erection is achieved. The patient is advised that he may require a lower dose at home in a more relaxed setting. No more than three injections per week may be administered no sooner than 24 hours apart. The cost of these formulations is approximately $5 per injection.
After an appropriate dose is determined, the patient is given a prescription and instructed to report any adverse event with at-home use. Patients are advised not to inject if the penis is partially erect since this increases penis outflow and medication is carried away and thus less effective in developing and sustaining an erection. Follow-up is at two weeks and every 2–6 months thereafter.
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Other pharmacological interventions for the treatment of erectile dysfunction include yohimbine hydrochloride, an alpha-2-adrenergic blocking agent. Yohimbine has long been considered an aphrodisiac. In a prospective double-blind placebo-controlled study in patients with predominately organic disease, including patients with diabetes related impotence, yohimbine did not show a statistically significant response rate over placebo control.
Twenty-one percent of patients did have some response with yohimbine. Treatment of erectile dysfunction due to diabetes with hormones is effective only if the patient also suffers from hypogonadal disorders or hyperprolactinemia. Testosterone replacement therapy in treating diabetes related erectile dysfunction should only be prescribed if a proper workup of the patient has been done. Oral administration of testosterone is unpredictable and therefore, parenteral administration is often prescribed as testosterone enanthate, which is administered intramuscularly in doses of 200–300 mg every 2–3 weeks.
Iprostadil
Phentolamine
Alprostadil
Papaverine
Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.