Erectile Dysfunction Medications
Drug therapy for erectile dysfunction was revolutionized with the introduction of phosphodiesterase-5 inhibitors. Until this time it was either a matter of luck with intraurethral alprostadil or a painful and risky procedure of intracavernosal injection with drugs like alprostadil and papaverine. The current treatment approaches primarily revolve around the phosphodiesterase-5 inhibitors like sildenafil.
Phosphodiesterase-5 (PDE-5) inhibitors
Sildenafil, taladafil and vardenafil are the selective PDE-5 inhibitors currently available commercially. All are prescription medicines in the United States and are available as oral tablets. The cyclic-GMP PDE-5 enzyme is believed to be the primary type of phosphodiesterase enzyme present in the cavernosal tissue of the penis. Sexual stimulation leads to increased levels of GMP in the cavernosal tissue of the penis. Cyclic GMP is a muscle relaxing chemical which allows for increased blood flow to the penis and filling of the corpora cavernosa.
Inhibition of the PDE-5 enzyme results in persistence of the GMP and its effects on cavernosal tissue. This results in the enhanced rigidity and enlargement of penis. Therefore PDE-5 inhibitors are an effective therapeutic option in erectile dysfunction. More than 50% of the patients suffering from erectile dysfunction find improvement with PDE-5 inhibitors. Individuals suffering from erectile dysfunction resulting from spinal cord injuries, radiotherapy of pelvis and diabetes mellitus may also experience some improvement with PDE-5 inhibitors. Men with erectile dysfunction due to reduced testosterone (hypogonadism) and low libido may be treated with a combination of testosterone therapy with PDE-5 inhibitors. PDE-5 inhibitors do not have any significant benefit in the absence of any sexual stimulation.
Side Effects and Contraindications
Headache, flushing, dyspepsia and nasal congestion are some of the common side effects seen with PDE-5 inhibitors as with many other drugs. Allergic reactions may be occur with the use of PDE-5 inhibitors and present with rashes and itching of the skin. Simultaneous intake some of the antifungal drugs (like itraconazole), antibiotics (like clarithromycin) and anti-HIV drugs (like ritonavir) are known to increase levels of the PDE-5 inhibitors. Hence dosage adjustment for PDE-5 inhibitor is required when patients are on thesedrugs. PDE-5 inhibitors may also sometimes be associated with some serious side effects as discussed below.
One of the serious adverse effects is a severe fall in blood pressure and the patients usually manifest with giddiness, fainting and palpitations which is more likely to arise in patients using nitrates (angina pain relief medication). PDE-5 inhibitors are generally contraindicated in individuals on nitrates. Patients on nitrates may still be given short acting PDE-5 inhibitors (like sildenafil) with at least 6 hours of gap between use of the nitrate and the ingestion of PDE-5 inhibitor. Individuals on other vasodilators (antihypertensive drugs including alpha-blockers that may also be given for prostate problems) are prescribed PDE-5 inhibitors with caution. There is risk of cardiac events during sexual activity in a person with heart disease. This also makes PDE-5 inhibitor therapy inadvisable in individuals at risk of cardiac events.
Rarely PDE-5 inhibitors can cause painful erection (priapism) or prolonged erection. Medical attention is recommended for priapism and erections that are longer than 4 hours. Delay in seeking medical assistance in these conditions may lead to damage to penile tissue and even permanent loss of potency.
Visual disturbances, altered color vision, and sudden loss or impairment of vision in one or both the eyes may be rarely associated with use of PDE-5 inhibitors. This may be due to development of a condition called as NAION (non-arteritic anterior ischemic optic neuropathy). Individuals past 50 years of age, smokers, diabetics, those with uncontrolled hypertension or with a history visual disturbances are at an increased risk of developing non-arteritic anterior ischemic optic neuropathy. A similar rare association with hearing loss or impairment in hearing is also seen with use of PDE-5 inhibitors.
Sildenafil was the first of the PDE-5 inhibitors to be introduced for erectile dysfunction. The recommended starting dose of sildenafil is 50 mg. The dose may be increased by 25 mg up to a dose of 100 mg or decreased 25 mg based on the response and side effects. It is taken when there is a need for an erection (on demand). The beneficial effects may be obtained when it is taken half an hour to 4 hours before sexual intercourse but it is ideally taken about one hour before the act. Only one dose is recommended in a day. Sildenafil is better avoided within one hour after intake of food.
Vardenafil is a PDE-5 inhibitor which is very much similar to sildenafil, except that vardenafil produces effects for slightly longer duration (about 6 hours). The treatment is usually started at a dose of 10 mg. The dose may be increased to a maximum of 20 mg per day or reduced to 5 mg, depending on the response and side effects. Vardenafil is recommended only once a day and is ideally taken one hour before intercourse. Vardenafil is not affected by food and may be taken before or after meals. It is also available as orally disintegrating tablets (Staxyn), which is placed under the tongue.
Taladafil is a quick-acting and long-acting PDE-5 inhibitor. The effect of the drug appears with in 15 minutes of ingestion and lasts for up to 36 hours. Taladafil may be used daily at a low dose of 2.5 mg. It may be taken at anytime without considering the timing for sexual intercourse. It may also be used on demand but at a higher dose of 10 mg. The dose may be increased up to 20 mg or decreased to 2.5 mg based on the clinical response and side effects.
Alprostadil is a prostaglandin E1 analogue. In the United States it is available for injection in the cavernosa and as intraurethral suppository. In some countries, it is also available as topical cream to be applied over the penis. Alprostail produces erection by its local vasodilatory effect on the cavernosal vessels. It is considered as a second line drug in erectile dysfunction.
It is may produce an erectile response in men who have failed to respond satisfactorily to PDE-5 inhibitors. Alprostadil is a fast acting drug that can be placed in the urethra or injected into the cavernosa about 10 to 15 minutes before the sexual intercourse. Some preparations of injectable alprostadil are available in combination with papaverine or phentolamine. The main drawback of injectable alprostadil is the painful injection that is required. Alprostadil use is generally associated with penile pain that is usually tolerable. Some individuals may suffer from priapism and prolonged erection with use of alprostadil.
Papaverine is an alkaloid obtained from the poppy plant. It is primarily used an antispasmodic drug. It is believed to exert its effects through inhibition of phosphodiesterase enzymes. Direct injection of the drug into the cavernosa produces prominent relaxation of smooth muscles and dilatation of cavernosal blood vessels. This results in the erection of penis.
Papaverine is useful in many patients with erectile dysfunction who are not responding to oral PDE-5 inhibitors. It is not available in certain countries. Pain during injection, priapism and prolonged erection are major drawbacks of papaverine. The papaverine injection may be combined with an alprostadil injection or phentolamine injection.
Phentolamine is an alpha-blocker. It is mainly used for treating hypertensive emergencies. It may be occasionally used for erectile dysfunction. It increases the blood flow to penis when administered by injection into the cavernosa.
Off-label use means that the medication, like apomorphine or trazadone, is not indicated for erectile dysfunction but may have some benefit in treating the condition. This, however, has not been conclusively proven.
Apomorphine has been found to stimulate the central nervous system (CNS) resulting in an arousal response with erection. However, the erection response produced with apomorphine no to the same degree as that btained with PDE-5 inhibitors. Apomorphine exerts its effects through the dopamine receptors in the CNS which increases the desire but not the blood flow to the penis. It may, however, be of use in individuals with diminished libido but not necessarily erectile dysfunction. The drug is not approved for use in the every country and is being discontinued in many countries where it was approved.
Trazodone is an antidepressant which may be occasionally used off-label for erectile dysfunction. It shows benefit in some men with ED. Sedation is an important side effect of trazadone and it is also known to produce priapism as a side effect.
Herbal remedies are based more often on empirical knowledge of its uses without scientific evidence to prove its beneficial effects for erectile dysfunction. Yohimbe and ginseng are some of the widely used herbal remedies used for ED.
Yohimbine is an alpha2-adrenergic blocker obtained from the plant Yohimbe. It has been reported to have beneficial effects in erectile dysfunction and is available in several herbal preparations meant for treatment of sexual dysfunction.
Ginseng is herbal product which is available in several countries as an aphrodisiac. It is believed to facilitate the erection of the penis and to enhance libido and the sexual performance.