by Georgina Lee, PharmD 2011 | firstname.lastname@example.org
Have you ever played a game at the arcade where the more accurately a person fires a steady stream of water into a target, the faster their object rises to the top? Imagine the person who sits down and pulls the trigger only to find the water stuck in the barrel. Do you blame the player for their inability to get their object to rise or do you blame the faulty water gun? For some men, having a faulty water gun can be both frustrating and debilitating, especially when it comes to bedroom activities. That’s probably why those little blue pills, otherwise known as Viagra, are flying off pharmacy shelves. These pills may not have Avatar-like abilities but they do serve as a miracle to some who suffer from one of nature’s most vexing problems.
What is erectile dysfunction (ED)?
The National Institutes of Health (NIH) defines male erectile dysfunction as the “inability to achieve or maintain an erection sufficient for satisfactory sexual performance.” Let’s not confuse ED, however, with other disorders such as premature or delayed ejaculation, anorgasmia (inability to achieve orgasm) or infertility. Essentially, there are four physiological systems that are necessary for a normal penile erection: vascular, neurologic, psychogenic and hormonal.
1. Vascular Stimuli
Erections are the result of shifting blood flow in the body. Most of the blood that is contained in the penis during an erection is in the corpora cavernosa (erectile tissues that lay along the penis shaft). Within the corpora cavernosa are multiple interconnected sinuses or sacs that can fill with blood to produce an erection. In the flaccid state (i.e. not erect), the arterial and venous blood flow into and out of the corpora are balanced. During an erection, however, arterial blood flow going into the corpora increases and blood fills the sinuses resulting in penile swelling and elongation. A neurotransmitter known as acetylcholine helps this process by enhancing production of nitric oxide and cAMP, which are substances that induce smooth muscle relaxation and vasodilation (widening of blood vessels). The erection is prolonged by a decrease in venous outflow from the corpora (so more blood stays in the penis). The take home message is that sufficient blood flow into the penis will cause an erection. Easy, right?
2 & 3. Neurologic and Psychogenic Stimuli
Of course blood flow is not the only important aspect of an erection. If you ask most men (or their wives), chances are some will have an erection while they are sleeping. This type of erection is mediated by a sacral nerve reflex arc. In the conscious person, however, sexual stimulation mediates erections via the central nervous system (the motherboard of nerves). In other words, someone who is awake can be stimulated by their senses (for example, if they see an attractive person, hear certain things, smell a particular scent, taste or touch a particular object…you see where this is going). No wonder the adult entertainment business is a billion dollar industry! The individual’s brain processes this sensory information and a nervous impulse is carried down the spinal cord to peripheral nerves (these nerves communicate via the neurotransmitter, acetylcholine). These nerves trigger an increase in the blood supply to the corpora and, like that, an erection is born! So what happens after an erection? The party has to stop at some point! A different neurotransmitter called norepinephrine is released. This chemical constricts vascular smooth muscle, decreasing arterial inflow to the corpora and increasing venous outflow (i.e. more blood leaves the penis). The end result is your standard flaccid penis, as good as new.
4. Hormonal Stimuli
The fourth system that is involved in the process of an erection has to do with testosterone which stimulates libido or sexual drive in males (or “Mojo” in the words of Austin Powers). Approximately one third of men older than 50 have a condition called hypogonadism that is characterized by low serum testosterone levels. When libido is decreased, a person may not develop erections and erectile dysfunction is considered secondary to a decreased libido. However, serum testosterone levels do not always correlate with ED so don’t kick down your doctor’s door demanding testosterone injections just yet.
Erectile dysfunction can manifest from any single or combination of abnormalities of the four systems necessary for a normal penile erection (and you used to think it was so simple). In addition, diseases that compromise vascular flow such as arteriosclerosis (stiffening of blood vessels), impair nerve conduction to the brain (i.e. stroke) or nerve conduction in the periphery (i.e. diabetes), mental disorders, hypothyroidism and others can all cause ED. Social habits such as smoking and drinking as well as certain medications have also been linked to performance problems (see it does happen to other guys).
How do I treat ED?
According to the American Urological Association (AUA), identifying underlying causes including disease states and psychosexual dysfunctions should be initiated followed by a heart-healthy lifestyle complete with a proper diet and regular exercise. If the person’s ED is not reversed after such changes, then the following pharmacological treatments can be considered by you and your primary care provider.
Phosphodiesterase Type 5 Inhibitors (PDE-5)
Most of us know what Viagra, Levitra, and Cialis are used for (thanks to their cuddly commercials) but how do they work? As mentioned earlier, acetylcholine helps release nitric oxide which causes vasodilation so more blood can flow into the penis in order to cause an erection. Nitric oxide does this by stimulating an enzyme that makes a substance called cGMP, which helps to produce a penile erection. Viagra, Levitra, and Cialis are all PDE-5 inhibitors meaning they block the enzyme (phosphodiesterase) that breaks down cGMP (making it inactive). When you take one of these medications, cGMP stays around longer and more blood goes into the penis to maintain an erection. In terms of efficacy, all three drugs are comparable depending on the person’s tolerance and satisfaction. Approximately 30-40% of patients do not respond to PDE-5 inhibitors mainly due to noncompliance issues. By “noncompliance issues” we mean:
Patients must engage in sexual stimulation for the best response
Sildenafil (Viagra) must be taken on an empty stomach at least 2 hours before meals (does not apply to Vardenafil (Levitra) or Tadalafil (Cialis))
Taking Viagra or Levitra with a fatty meal can decrease the absorption rate (Cialis is not affected)
Patients who do not respond to the first dose should continue with the drug for at least 5-8 doses before failure is declared, as increasing success rates are reported with sequential dose administration
Some patients require dosage titration up to 100mg of Viagra, 20mg of Levitra or 20mg of Cialis for a response
In general, Viagra and Levitra are similar in that they have a 1-hour onset of action, short duration of action and oral absorption that is significantly delayed when the drugs are taken within 2 hours of a fatty meal. In contrast, Cialis has a delayed onset of action of 2 hours, a prolonged duration of action of up to 36 hours and food does not affect its rate of absorption. People taking these medications should avoid alcohol as it may result in orthostatic hypotension (low blood pressure upon standing up) and cause symptoms such as lightheadedness and dizziness. The most common side effects for these medications include headache, facial flushing, dyspepsia (stomach irritation) and dizziness (super sexy, right?). Also, people taking nitrates (nitroglycerin or isosorbide dinitrate) for chest pain should not take these medications.
Intra-Cavernosal & Intra-Urethral Alprostadil (Caverject, Edex, and MUSE)
Alprostadil is a drug that stimulates production of cAMP which causes smooth muscle relaxation of the arterial blood vessels of the penis, enhancing blood flow. It can be injected either directly into the corpora cavernosum (side of the penis) or into the urethra (front of the penis). Yes, we did just say “injected.” Although it is highly efficacious, 30-50% of patients voluntarily discontinue therapy during the first 6-12 months due to inconvenience of administration, an unnatural nonspontaneous erection, needle phobia, loss of interest, and cost of therapy. We would wager that “needle phobia” is the big winner in that group. Typically, the onset of action occurs within 5-15 minutes and the duration can last for up to an hour…assuming you don’t pass out from the needle.
Testosterone Replacement Agents
Testosterone replacement regimens restore testosterone levels to the normal range (300-1,100 ng/dL) which can correct symptoms of hypogonadism (symptoms include malaise, loss of muscle strength, depressed mood, and decreased libido). In addition, testosterone can stimulate nitric oxide which can enhance blood flow into the penis. Testosterone can be administered orally, parenterally (injection), or transdermally (gel or patch). Injectable testosterone is the preferred treatment for symptomatic patients because the injections are effective, inexpensive, and not associated with major side effects. Although convenient for the patient, testosterone patches and gels are much more expensive than other forms and should be reserved for patients who completely refuse injectable testosterone (you didn’t hear that from us). Side effects from gels/patches include weight gain, high blood pressure, gynecomastia (man boobs). Also, FYI, the patches and gels should not be used when in close contact with pregnant women.
Hopefully we’ve opened your eyes to solutions out there beyond the little blue pill. That being said, we have a few more tricks up our sleeve before we wrap up. First, the vacuum erection device (VED) is a pump that is activated by the patient producing a vacuum pressure to draw arteriolar blood into the corpora cavernosa. The onset of action is comparatively slow (30 minutes), which requires patience and planning from both the patient and the sexual partner. Not to mention the fact that VEDs are not very discreet (read: hard to hide). Other unapproved agents include trazodone, yohimbine, papaverine and phentolamine. The most invasive treatment for ED is the surgical insertion of a penile prosthesis used for people who do not respond to oral or injectable treatments. Penile prostheses provide penile rigidity suitable for vaginal intercourse and are associated with a greater than 90% patient satisfaction rate (generally higher than that observed with any other drug treatment or VED). Much easier to use, a number of device options to choose from but, at the same time, an invasive procedure to say the least. We’ll let you make the final call.
A possible and potentially dangerous side effect of all of the above treatments is known as priapism (a prolonged and painful erection lasting for more than 1 hour). This complication becomes most dangerous when an erection persist beyond 4 hours (sounds painful) and people are thus advised to seek medical attention immediately since priapism is considered an urological emergency. Most importantly, seek professional medical advice from your primary care provider before starting any treatment. Erectile dysfunction is a very personal issue and difficult to discuss yet the condition is very manageable with proper medical examination and treatment. With your ED under control, we’ll leave you with one more valuable piece of medical advice: Always remember to practice safe sex (don’t be a fool, wrap your tool)!
Questions? E-mail the Author: email@example.com
DiPiro, Joseph T. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill, 2008. 1369-385. Print.
American Urological Association Education and Research. “AUA Guideline on the Management of Erectile Dysfunction: Diagnosis and Treatment Recommendations.” AUA – Home. 2005. Web. 03 June 2010. <http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines>.
NIH Consenus Conference. NIH Consensus Development Panel on Impotence. Impotence. JAMA 1993;270:83-90.
Stimmel & Gutierrez. Counseling about sexual issues. Pharmacotherapy 2006;26: 1608-1615.