Erectile Dysfunction Medication

  • Author: Edward David Kim, MD, FACS; Chief Editor: Edward David Kim, MD, FACS   more...
 
Updated: May 1, 2012
 

Medication Summary

An increasing array of medications is available to assist in the management of erectile dysfunction (ED). New agents are still undergoing clinical testing, and more are in the early phases of development.

For any medication to be effective, the physiologic components involved in the erectile process must be functional. Serious impairments render the medication either completely or partially ineffective.

An ideal agent should be rapidly effective, easy to administer, affordable, applicable to a wide range of patients, and minimally toxic. The types of medications can be divided into oral, topical, injectable, and intraurethral insertion. Phosphodiesterase (PDE) type 5 inhibitors are the principal oral agents used in ED.[61]

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Phosphodiesterase-5 Enzyme Inhibitors

Class Summary

At least 7 phosphodiesterase (PDE) classes are known, many with subtypes identified by structure and function. This drug class consists of sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis), and avanafil (Stendra). Sildenafil was the first in this series of PDE inhibitors. The newer agents are more specific and potent cGMP inhibitors than sildenafil. All of the agents are PDE-5 inhibitors, but the newer drugs in the class are significantly more selective in their inhibition. PDE-5 is cGMP specific and is a major cGMP-hydrolyzing enzyme in the vascular smooth muscle of the penis. The agents rely on the role of nitric oxide (NO) in inducing vasodilatation. NO relaxes the smooth muscle of the corpora cavernosa peripherally by stimulating guanylyl cyclase activity, which raises the intracellular concentrations of the cyclic nucleotide cGMP, which, in turn, induces vasodilation.

Intracellular cGMP is hydrolyzed by PDEs, terminating their action. PDEs are a diverse family of enzymes with different tissue distributions and functions, but all exert their effect by lowering intracellular cyclic nucleotide levels.

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Sildenafil (Viagra)

 

Sildenafil is a PDE-5 selective inhibitor. Inhibition of PDE-5 increases cGMP activity, which increases vasodilatory effects of NO.

Sildenafil is most effective in men with mild-to-moderate ED. It is to be taken on an empty stomach approximately 1 hour before sexual activity. Sexual stimulation is necessary to activate response.

Sildenafil is available as 25-, 50-, and 100-mg tablets. The onset of action varies from 15-60 minutes, with a duration of action of 4-6 hours. Its half-life is 4-5 hours.

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Vardenafil (Levitra)

 

Vardenafil is a PDE-5 selective inhibitor. Inhibition of PDE-5 increases cGMP activity, which increases vasodilatory effects of NO.

Vardenafil is effective in men with mild-to-moderate ED. It is to be taken on an empty stomach approximately 1 hour before sexual activity. Sexual stimulation is necessary to activate response. Increased sensitivity for erections may last 24 hours.

It is available as 2.5-, 5-, 10-, and 20-mg tablets. Vardenafil acts within 15-30 minutes and can be taken with food, although a high-fat meal can inhibit absorption. Its half-life is 4.8-6 hours.

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Tadalafil (Cialis)

 

Tadalafil is a novel PDE-5 selective inhibitor chemically unrelated to sildenafil and vardenafil. It is most effective for mild-to-moderate ED of varying etiologies, including both organic and psychogenic causes.

PDE-5 inhibition increases cGMP activity, which increases vasodilatory effects of NO. Sexual stimulation is necessary to activate response. Because sexual stimulation is required to initiate local release of NO, tadalafil has no effect in the absence of sexual stimulation. Increased sensitivity for erections may last 36 hours with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (eg, twice weekly); men can attempt sexual activity at any time between daily doses.

Tadalafil is available as 2.5-, 5-, 10-, and 20-mg tablets. The major difference between tadalafil and the other PDE-5 inhibitors is its longer half-life of 17.5-21 hours compared with sildenafil (4-5 h) and vardenafil (4.8-6 h). In patients who respond, coitus has been recorded from 30 minutes to 36 hours after administration.

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Avanafil (Stendra)

 

Avanafil is a PDE-5 inhibitor that inhibits cGMP degradation and, thereby, enhances the effects of NO in smooth muscle relaxation of the corpus cavernosum.

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Vasodilators

Class Summary

Some agents injected directly into the penis exert their relaxant effect directly on the corpora cavernosal smooth muscle. They can be used as single agents or in combination. The most commonly used agents include alprostadil (prostaglandin E1 [PGE1]), papaverine, and phentolamine. The dose and most effective combination of these agents must be determined for each patient.

These medications can be obtained commercially as Caverject and Edex or can be formulated according to the physician's request by compounding pharmacies. Patients can be supplied with vials of a single agent or a combination of agents mixed in a single vial. Patients must be instructed in the proper technique for administration.

A single intraurethral agent, PGE1, which has been formulated into a small suppository, is commercially available as Medicated Urethral System for Erections (MUSE). This agent was available prior to the introduction of sildenafil and is still used by a select group of men.

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Alprostadil (Caverject, Edex, MUSE)

 

Alprostadil is identical to naturally occurring PGE1 and has various pharmacologic effects, including vasodilation and inhibition of platelet aggregation. When injected into the penile shaft, it relaxes trabecular smooth muscle, dilating cavernosal arteries, which, in turn, promotes blood flow and entrapment in the lacunar spaces of the penis, causing penile erection. Various doses have been used.

Commercially, Caverject is available in doses of 10-40 mcg, but a number of pharmacists and physicians prepare PGE1 in doses appropriate to the individual patient.

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Papaverine

 

Papaverine is a benzylisoquinoline derivative with direct nonspecific relaxant effect on vascular, cardiac, and other smooth muscle.

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Phentolamine

 

Phentolamine is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on the alpha-receptors.

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Androgens

Class Summary

Androgens are primarily of benefit in men with low levels of serum testosterone. Men with hypogonadism who desire a restoration of libido and who wish to become sexually active usually benefit from the exogenous supplementation of androgens. This can be accomplished with injections, cutaneous application via gel or skin patches, or oral administration.

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Testosterone (AndroGel, Axiron, Depo-Testosterone, Testopel, Testim, Androderm, Striant, Fortesta)

 

Testosterone promotes and maintains secondary sex characteristics in androgen-deficient males. Depot injections can produce high levels of serum testosterone when administered in adequate doses.

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Contributor Information and Disclosures
Author

Edward David Kim, MD, FACS  Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, Sexual Medicine Society of North America, and Tennessee Medical Association

Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching

Coauthor(s)

Stanley A Brosman, MD  Clinical Professor, Department of Urology, University of California, Los Angeles, David Geffen School of Medicine

Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for Cancer Research, American Association for the Advancement of Science, American College of Surgeons, American Medical Association, American Society of Clinical Oncology, American Urological Association, Association of Clinical Research Professionals, International Society of Urological Pathology, Société Internationale d'Urologie (International Society of Urology), Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, and Western Section American Urological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Martha K Terris, MD, FACS  Professor, Department of Surgery, Section of Urology, Director, Urology Residency Training Program, Medical College of Georgia; Professor, Department of Physician Assistants, Medical College of Georgia School of Allied Health; Chief, Section of Urology, Augusta Veterans Affairs Medical Center

Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mark Jeffrey Noble, MD  Consulting Staff, Urologic Institute, Cleveland Clinic Foundation

Mark Jeffrey Noble, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Kansas Medical Society, Sigma Xi, Society of University Urologists, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Chief Editor

Edward David Kim, MD, FACS  Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, Sexual Medicine Society of North America, and Tennessee Medical Association

Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching

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These images depict penile anatomy. Note the sinusoidal makeup of the corpora and thick fascia (ie, Buck fascia) that covers the corpora cavernosa. The major blood vessels to the corpora cavernosa enter through tributaries from the main vessels running along the dorsum of the penis.
Vascular anatomy of the penis.
This penile tumescence monitor is placed at the base and near the corona of the penis. It is connected to a monitor that records a continuous graph depicting the force and duration of erections that occur during sleep. The monitor is strapped to the leg. The nocturnal penile tumescence test is conducted on several nights to obtain an accurate indication of erections that normally occur during the alpha phase of sleep.
The presence of normal skin sensation adequate to produce an erection is measured with this device.
A vasodilator such as prostaglandin E1 can be injected into one of the corpora cavernosa. If the blood vessels are capable of dilating, a strong erection should develop within 5 minutes.
Erectile dysfunction. This diagram depicts a cross-section of penile anatomy and is used to instruct patients in the technique of administering intracorporeal medications.
The Medicated Urethral System for Erections (MUSE) is a small suppository placed into the urethra with this device.
This image depicts a vacuum device used to produce an erection (also see next image). In this image, the elements are shown. They include the cylinder, a pump to create a vacuum, and a constriction ring to be placed at the base of the penis after an erection has been obtained in order to maintain the erection.
This image demonstrates the vacuum device in place (see previous image). Note the presence of the constricting ring at the base of the penis.
This is one of many types of constricting devices placed at the base of the penis to diminish venous outflow and improve the quality and duration of the erection. This is particularly useful in men who have a venous leak and are only able to obtain partial erections that they are unable to maintain. These constricting devices may be used in conjunction with oral agents, injection therapy, and vacuum devices.
Two rigid cylinders have been placed into the corpora cavernosa. This type of implant has no inflation mechanism but provides adequate rigidity to the penis to allow penetration.
This inflatable penile prosthesis has 3 major components. The 2 cylinders are placed within the corpora cavernosa, a reservoir is placed beneath the rectus muscle, and the pump is placed in the scrotum. When the pump is squeezed, fluid from the reservoir is transferred into the 2 cylinders, producing a firm erection. The deflation mechanism is also located on the pump and differs by manufacturer.
Table 1. Diseases and conditions associated with ED
Vascular causesAtherosclerosis



Peripheral vascular disease



Myocardial infarction



Arterial hypertension



Vascular injury from radiation therapy



Vascular injury from prostate cancer treatment



Blood vessel and nerve trauma (eg, due to long-distance bicycle riding)



Medications for treatment of vascular disease



Systemic diseasesDiabetes mellitus



Scleroderma



Renal failure



Liver cirrhosis



Idiopathic hemochromatosis



Cancer and cancer treatment



Dyslipidemia



Hypertension



Neurologic causesEpilepsy



Stroke



Multiple sclerosis



Guillain-Barré syndrome



Alzheimer disease



Trauma



Respiratory diseaseChronic obstructive pulmonary disease



Sleep apnea



Endocrine conditionsHyperthyroidism



Hypothyroidism



Hypogonadism



Diabetes



Penile conditionsPeyronie disease



Epispadias



Priapism



Psychiatric conditionsDepression



Widower syndrome



Performance anxiety



Posttraumatic stress disorder



Nutritional statesMalnutrition



Zinc deficiency



Hematologic diseasesSickle cell anemia



Leukemias



Surgical proceduresBrain and spinal cord procedures



Retroperitoneal or pelvic lymph node dissection



Aortoiliac or aortofemoral bypass



Abdominal perineal resection



Proctocolectomy



Transurethral resection of the prostate



Radical prostatectomy



Cryosurgery of the prostate



Cystectomy



MedicationsAntihypertensives



Antidepressants



Antipsychotics



Antiulcer agents (eg, cimetidine)



5-Alpha reductase inhibitors (eg, finasteride, dutasteride)



Cholesterol-lowering agents



Table 2. Penile Implants for Erectile Dysfunction
Treatment Advantages Disadvantages
Semirigid or malleable rod implantsSimple surgery



Relatively few complications



No moving parts



Least expensive implant



Success rate of 70-80%



Highly effective



Constant erection at all times



May be difficult to conceal



Does not increase width of penis



Risk of infection



Permanently alters or may injure erection bodies



Most likely implant to cause pain or erode through skin



If unsuccessful, interferes with other treatments



Fully inflatable implantsMimics natural process of rigidity-flaccidity



Patient controls state of erection



Natural appearance



No concealment problems



Increases width of penis when activated



Success rate of 70-80%



Highly effective



Relatively high rate of mechanical failure



Risk of infection



Most expensive implant



Permanently alters or may injure erection bodies



If unsuccessful, interferes with other treatments



Self-contained inflatable unitary implantsMimics natural process of rigidity-flaccidity



Patient controls state of erection



Natural appearance



No concealment problems



Simpler surgery than fully inflatable prosthesis



Success rate of 70-80%



Highly effective



Sometimes difficult to activate the inflatable device



Does not increase width of penis



Mechanical breakdowns possible



Long-term results not available



Risk of infection



Relatively expensive



Permanently alters or may injure erection bodies



If unsuccessful, interferes with other treatments



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