Etiology and Risk Factors of ERD – Online Pharmacy News

Etiology and Risk Factors of ERD

Vascular disease is the most common etiology of ERD in elderly men. The risk of vascular ERD increases with smoking, hyper-cholesterolemia, and diabetes. In addition, many diseases, such as diabetes, stroke, and Parkinson’s disease, can cause autonomic dysfunction. This can impair the penile arterial vasodilatation, maintaining the vascular constriction, and therefore preventing erection. Furthermore, a number of medications have been associated with ERD. Medications with anticholinergic properties, such as antidepressants, anti-psychotics, and antihistamines, block parasympathetic-mediated penile artery vasodilatation and trabecular smooth muscle relaxation.⁸ Causes contributing to ERD may be related to a number of disorders, which are listed in Table 2.

ERD is clearly a symptom of many conditions, and certain risk factors have been identified, some of which may be preventable. Diabetes mellitus, hypogonadism, hypertension, vascular disease, high cholesterol or low-density lipoprotein cholesterol, alcohol ingestion, depression, lack of sexual knowledge, poor sexual techniques, and many chronic diseases have all been identified as risk factors. In addition, age is a strong indirect risk factor because it may be associated with increased likelihood of direct risk factors. Smoking is another indirect risk factor that may increase the effects of other risk factors, such as hypertension or vascular disease. Knowledge of the risk factors can guide patients to prevention strategies.

Diagnosis of ERD

ERD may be associated with several abnormalities of the endocrine, neurological, and vascular system. Thus, an appropriate evaluation of all men with ERD should include a medical and sexual history, physical exam, psychosocial evaluation, and appropriate laboratory studies.³

Endocrine evaluation includes hemoglobin A1C, a morning serum testosterone, prolactin, luteinizing hormone, and follicle-stimulating hormone (FSH) levels. Other tests, such as complete blood count, urinalysis, creatinine, lipid profile, fasting blood sugar, and thyroid function may be indicated to exclude an unrecognized underlying systemic disease. Neurologic causes may be associated with a history of diabetes, spinal injury, or cerebrovascular accident; a detailed medical history will be essential to identify them. In addition, nocturnal penile tumescence testing may be useful when a primary psychogenic ERD is suspected. An erectile response to an intracavernosal injection of pharmacological test dose of a vasodilatory agent, such as papaverine or PGE1, indicates adequate arterial and veno-occlusive function. For patients who favor noninvasive treatments, such as the oral PDE5 inhibitors, pharmacological injection, intraurethral suppository, or vacuum constrictor devices, no further diagnostic tests are necessary. On the other hand, for patients with unsatisfactory response, penile implant surgery or further diagnostic tests may be appropriate.³

■■ III. Pharmacology/Pharmacodynamics

FDA-Approved Therapy

Alprostadil (Caverject, Edex, and MUSE)

Prostaglandin E1 (alprostadil) is one of the prostaglandins, naturally occurring acidic lipids with a variety of pharmacological effects, including vasodilatation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle. It acts by relaxing the trabecular smooth muscles of the corpus cavernosum and increasing the diameter of cavernous arteries, and this leads to erection. In animal studies, the degree and duration of cavernous smooth muscle relaxation appears to be dose dependent.^11-13

^{TABLE 3} Selectivity Ratios for PDE5 Inhibitors Versus Other PDE Isoenzymes^14-18

PDE5 Inhibitors ( Viagra for sale myviagrainaustralia.com, Vardenafil, and Tadalafil)

The mechanism of penile erection involves relaxation of the corpus cavernosal smooth muscle. This occurs through release of nitric oxide during sexual stimulation, which results in increased concentrations of cGMP. Sildenafil, vardenafil, and tadalafil are all competitive inhibitors of the type 5 cGMP-specific PDE5 enzyme.^14-16 The result is an enhancement of the effect of nitric oxide secondary to a decrease in degradation of cGMP. PDE5 inhibitors have no effect in the absence of sexual stimulation.

There are 11 families of phosphodiesterase isoenzymes that have been identified in mammalian tissue. While PDE1 through 6 have been extensively studied, PDE7 through 11 have been recently discovered, and thus less is known regarding their distribution and function in the human body.

Sildenafil, vardenafil, and cialis australia are all more selective for the PDE5 isoenzyme than for all other PDE isoenzymes. However, degrees of selectivity vary among the agents, depending on the isoenzyme in question. As illustrated in Table 3, sildenafil is 80 times more selective for PDE5 than for PDE1, but greater than 80 times more selective for PDE6, an isoenzyme heavily concentrated in the retina of the eye.^17,18 In contrast, tadalafil is greater than 700 times more selective for PDE5 than for the PDE6 isoenzyme. This selectivity ratio pattern may explain why the side effect of blue-tinged vision or changes in blue-green color discrimination is reported with sildenafil canadian pharmacy but is not expected to occur with tadalafil use. On the other hand, tadalafil is only 14 times more selective for the PDE5 than the PDE11 isoenzyme than sildenafil and vardenafil, which have much higher selectivity ratios. The low selectivity ratio of tadalafil for PDE11, an isoenzyme heavily concentrated in the testes and skeletal muscle, led investigators to conduct safety studies to ascertain what effect tadalafil would have on sper-matogenesis. However, 6-month, daily-dosing, placebo-controlled studies with 10 and 20 mg/day of tadalafil produced no clinically relevant effect on spermatogenesis as measured by sperm count and sperm morphology and motility. Additionally, no effect was observed on hormones related to spermatogenesis (luteinizing hormone, FSH, testosterone) with chronic tadalafil use.¹⁹