Browsing Posts published in June, 2013

Vasoactive Medications

The penis is composed of two twin erectile chambers, the corpora cavernosa, which are surrounded by an elastic membrane called the tunica albuginea that stretches with an erection until the cavities become three times larger in size as this covering reaches its limit of stretch. The components of these two cavities are numerous cul-de-sacs, or endothelial-lined spaces surrounded by smooth muscle. For further information on the anatomy and physiology of the penis, see the chapters in Part I of this volume.

Agents that cause relaxation of this smooth muscle are very effective in allowing blood to flow into the penis, expanding the sinusoids and compressing subtunical venules to hold blood in the penis and to generate an erection. Conversely, agents that cause contraction of the smooth muscle are effective in reducing a prolonged erection (priapism). In recent years, a number of agents have emerged in various forms that affect the smooth muscle surrounding the sinusoids. As with many muscle cells elsewhere in the body, when the calcium content of the cell is lowered, the penile smooth muscle will relax. There are various transmitter substances, which, when released from nerve endings, will diffuse across the intercellular space to stimulate the enzyme systems within these smooth-muscle cells, eventually resulting in the loss of calcium from the cell and producing muscle relaxation. Nitric oxide has recently been discovered as one of the major transmitters that affects this action in penile smooth-muscle cells.

Oral Medications

The recent introduction of sildenafil citrate new zealand (Viagra) and subsequently vardenafil (Levitra) and tadalafil (Cialis) has revolutionized the treatment of erectile dysfunction. These compounds are type V phosphodiesterase inhibitors, and under the influence of sexual stimulation, have been found to be beneficial in enhancing and prolonging erections. When nitric oxide is released from nerve terminals, it diffuses across the interspace to the penile smooth-muscle cell, where it influences the guanyl cyclase enzyme system. This converts GTP to cyclic GMP, which results in decreased intracellular calcium concentration and smooth-muscle relaxation. Type V phosphodiesterase is the enzyme that degrades cyclic GMP to its metabolite. When this enzyme is inhibited by these compounds, cyclic GMP levels stay high, calcium stays out of the cell, and the smooth muscle stays relaxed.

For the three available type V phosphodiesterase inhibitors to work effectively, sexual stimulation is necessary and the penile nerves need to be intact in order to release nitric oxide. Absorption of these agents in the gastrointestinal tract is relatively rapid, and effects are sometimes seen in as short a time as 20 minutes after ingestion. Peak absorption occurs at 0.8 hours, and the drug’s half-life is between four and five hours for sildenafil and vardenafil. The window of opportunity for sexual activity with both of these agents is usually even beyond the five-hour half-life noted. By 24 hours, they are completely gone from the body. Tadalafil has a longer half-life of 17 hours and may be effective for up to 36 hours after ingestion. Overall, the success rate with the type V phosphodiesterase inhibitors has been 80% in psychogenic impotence and about 60% in organic erectile dysfunction.

Generally, the two groups of patients who do not respond as well to phosphodiesterase inhibitors are those with diabetes mellitus and those who have had radical prostatectomy. In clinical trials, the response in the latter group was 43%.

– If bilateral nerve-sparing prostatectomy has been performed, the response rate with sildenafil in patients who were previously potent is 72%.

– If only one nerve was spared during the prostate ablative procedure, the response rate with sildenafil falls to the range of 50%.

– If both nerves were removed during the prostatectomy, only a 15% positive response is seen.

These drugs have also been effective to some degree in patients whose erections have been diminished following brachytherapy or external beam radiation.

Side effects of these medications include headache, flushing, and dyspepsia. These side effects are uncommon and usually very well tolerated. They also tend to diminish with time as patients continue to take the medication. There have been a number of deaths reported in conjunction with the use of these drugs, but more recent studies have shown that they have no significant effect on the heart. A study of patients with cardiac disease measured cardiac dynamics before and after ingestion of sildenafil and found no difference— i.e., no effect of this medication on the heart muscle and function.

It should be noted, however, that there has been some synergy of type V phosphodiesterase inhibitors with nitrates in lowering the blood pressure, and for this reason, the American College of Cardiology has recommended that nitrates and these medications not be used simultaneously. In addition, phosphodiesterase inhibitors should be used with extreme caution in patients with congestive heart failure, myocardial disease, or in those on a complex antihypertensive regimen. In one set of clinical trials, no priapism was seen in patients using sildenafil; this was, however, a controlled group, and the medications that patients were taking in addition to the trial drug were limited. Now that these compounds are readily available, patients are using cocktails or mixtures with other treatments that enhance erections. In addition, they may be using these medications combined with other medicines that predispose to priapism, such as thioridazine (Mellaril), trazodone, or the phenothiazine compounds. Under these circumstances, prolonged, painful, and unwanted erections have been seen. The advent of sildenafil in 1998 has broadened the awareness of erectile dysfunction as a problem related to various disease processes. This awareness has brought many new patients into the clinic for treatment. Before the introduction of sildenafil, yohimbine (Yocon) was the most commonly prescribed treatment for erectile dysfunction. Most studies, however, have failed to demonstrate any significant benefit of yohimbine over placebo in the treatment of poor erections. A number of other oral preparations are now under study and in clinical trials for the treatment of erectile dysfunction. Intracorporal Injections – viagra sydney australia.

At the American Urological Association meeting in Las Vegas in 1983, Dr. Giles Brindley, a British pharmacologist, dramatically and memorably illustrated the effectiveness of intracorporal injections of papaverine by demonstrating to the audience his own erection induced by this medication. Following this graphic display, the use of this agent and other intracorporal injections rapidly gained popularity. Now, papaverine, phentolamine, and prostaglandin E1 (PGE1) (Caverject) (EDEX) alone or in combination are used effectively in generating an erection with up to 80% success. Both papaverine and PGE1 act directly on penile smooth-muscle cells via the cyclic AMP pathway to cause smooth-muscle relaxation by decreasing intracellular calcium. When injected into one portion of the penis, this effect is rapidly spread throughout the entire length of both corporal bodies by gap junction or cell-to-cell transmission. Phentolamine is a selective α-adrenergic adrenoceptor blocker that inhibits sympathomimetic amines such as norepinephrine and blocks contraction of penile smooth-muscle cells. It acts synergistically with papaverine and PGE1, but has not been practically effective by itself in generating an erection by intracorporal injection.

Almost 90% of patients following nerve-sparing radical prostatectomy will respond to intracavernosal PGE1, in contrast to only 66% of patients who have had non–nerve-sparing procedures. In addition, nearly 25% of the nervesparing prostatectomy patients who have responded did so at a low dose of PGE1, in contrast to those with non–nerve-sparing procedures, who required high doses of the same medication.

PGE1 may result in pain in some patients, and this is particularly distressing in cases of neurapraxia, which may be seen following prostatectomy. Montorsi et al. have shown that instituting intracavernous injections of PGE1 very shortly (two months) after performing radical prostatectomy will result in a return of spontaneous erections without medication at one year in 67% of patients. In a controlled group that was not treated with intracavernous injections of PGE1, only 20% of patients noted the spontaneous return of erections by that time interval. The exact mechanism for this is unknown, but it may be related to the prevention of a buildup of transforming growth factor in the low oxygen states associated with reduced penile blood flow. This leads to the occurrence of fibrosis in penile muscles. In the aging patient, it is well known that the more erections are used, the better they tend to work. Abstinence from sexual activity for a period of time as is necessitated by a surgical procedure and the subsequent recovery period is certainly contributory to sexual dysfunction in this regard. When approaching patients who are impotent before nerve-sparing prostatectomy, the surgeon should be aware that pharmacotherapy afterward will be more effective if the nerves have been spared. Priapism or prolonged painful erection has been seen about 7% of the time with papaverine and phentolamine and about 1% of the time using PGE1. Such erections are usually easily reversed using dilute sympathomimetic amine solutions such as epinephrine or phenylephrine injected intracorporally. The incidence of development of corporal fibrosis (i.e., penile plaques) varies from 1.9% to 16% in patients using a pharmacologic erection program. This can be minimized by less frequent use (less than twice a week), varying the site of injection, and compressing the site of injection for a period of about 30 seconds to prevent internal bleeding. Long-term follow-up studies with patients on intracorporal injections show a relatively high dropout rate in the range of 70% over three years. Reasons for discontinuation of therapy include a desire for a permanent treatment alternative, fear of injections with needles, poor response, lack of a suitable partner, comorbid health conditions precluding comfortable positions for intercourse, and loss of sexual spontaneity.

Ejaculation

As men age or undergo surgical procedures that result in the loss of erection, ejaculation is usually preserved. This function consists of two components: “emission,” or the placement of semen in the prostatic urethra, and “ejaculation,” or the forceful expulsion of semen to the urethra and out the urethral meatus in a rhythmic fashion. During emission, the bladder neck or internal sphincter closes, and the prostatic muscles contract with the resultant expressing of semen or prostatic fluid into the prostatic urethra. During the ejaculatory phase, the rhythmic contraction of the vas deferens propels sperm to the prostatic urethra to mix with the seminal fluid and the rhythmic contraction of the bulbocavernosus and ischiocavernosus muscles propels the semen in spurts along the urethra and out the meatus.

With radical prostatectomy, the emission phase is lost, since there is no prostate to expel semen into the urethra and the vas deferens has been ligated. The ejaculatory phase, however, may be preserved and patients following radical prostatectomy will frequently reach climax – female viagra canada with adequate sexual stimulation. There is a feeling of pleasure and relief with the rhythmic contractions of the bulbous muscles but no elimination of fluid.

Other forms of treatment for prostate cancer, such as external beam therapy and brachytherapy do not significantly affect ejaculation per se. Premature ejaculation does not seem to be age dependent because it appears to be equally prevalent in younger and older men. Less direct, tactile stimulation prior to penetration, the use of distracting maneuvers such as the squeeze technique , and biofeedback exercises have all been used in the past with modest success. Recently, it has been found that the selective serotonin reuptake inhibitors (SSRIs) such as Paxil (paroxetine) 20 mg, given two to four hours prior to ejaculation, have been effective in 80% of the cases in prolonging ejaculatory latency.

Counseling

As mentioned previously, prostate cancer is a disease of aging and is almost unheard of before the age of 40. As men reach this milestone, erections become less reliable. It should be noted, however, that each man’s particular environmental circumstance plays a major role in whether erection can be satisfactorily achieved. For example, if the patient is rested, erections will be easier to produce than when he is tired. Similarly, if the patient is distracted by pain, career or financial worries, or other such concerns, he will be unable to focus on sexual activity. This is in contrast to a man’s younger years—i.e., the teens and twenties—during which concentration is not very necessary to achieve an erection. In young men, only slight stimulation is necessary to achieve a complete erection rapidly. Also, as one ages, the importance of a partner’s participation becomes greater, and with the partner’s help, an erection will be more readily achieved. In addition to these environmental influences, comorbid features such as smoking, obesity, diabetes mellitus, hypertension, and hyper lipidemia that may further contribute to erectile dysfunction should be discussed and appropriate treatment and a change in lifestyle advised. Even though the treatments of prostate cancer may have a detrimental effect on erections, such counseling may be very beneficial in improving marginal erectile function. To fight erectile dysfunction buy Kamagra Australia.

Male Hormone Replacement

Male hormone, testosterone, is below the normal level in 7% of men below age 60 and 20% of men above age 60. The gradual decline of testosterone levels with age, termed “andropause,” occurs at about 1% per year. If this circumstance occurs, sex drive may be low, erections may be problematic, and energy level or enthusiasm for the activities of life may be reduced. Replacement of the male hormone may improve each of these three problems. As previously discussed, one treatment of advanced prostate cancer is the reduction/removal of testosterone. To date, such a study has never been done, but by inference, testosterone in the normal range—or even in the supraphysiologic range, which may occur with intramuscular replacement—may stimulate the growth of prostate cancer. Hence, it is recommended that patients with known prostate cancer not be given testosterone replacement as a treatment for sexual dysfunction unless the cancer is considered cured and it is believed that the individual patients in question would comply completely with follow-up evaluations.