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Benign Prostatic Hyperplasia

Posted by admin on July 11th, 2011 No Comments

Definition Benign prostatic hyperplasia, a nearly ubiquitous condition, is the most common benign neoplasm of American men and occurs as a result of hormone-driven prostate growth. Pathophysiology The prostate gland comprises three types of tissue: epithelial or glandular, stromal or smooth muscle, and capsule. Both stromal tissue and capsule are embedded with О±1-adrenergic receptors. The precise pathophysiologic mechanisms that cause Benign prostatic hyperplasia are not clear. However, both intraprostatic dihydrotestosterone and type II 5 О±-reductase are thought to be involved. Benign prostatic hyperplasia commonly results from both static (gradual enlargement of the prostate) and dynamic (agents or situations that increase О±-adrenergic tone and constrict the gland's smooth muscle) factors. Examples of drugs that can exacerbate symptoms include testosterone, О±-adrenergic agonists (e.g., decongestants), anticholinergics (e.g., antihistamines, phenothiazines, tricyclic antidepressants, anticholinergic antispasmodics, Read more [...]

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Prostatitis: Advanced Therapy

Posted by admin on June 21st, 2011 No Comments

Prostatitis is one of the most perplexing disease entities with which the practicing urologist must contend. Also, the treatment of this disease is the least gratifying in that the patients often are labeled as "crazy" and have a poor response. In many ways, there are some significant similarities with interstitial cystitis, and perhaps some of the patients with complaints of prostatitis actually have interstitial cystitis, as has been suggested. Indeed, many of the symptoms and physical findings are similar and are outlined in Table 71-1. As in the case of interstitial cystitis, prostatitis has also been difficult to study, being a disease that lacked a formal and specific definition. Therefore, the National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDKD) convened a consensus group to define prostatitis, expressly for the purpose of describing the different prostatitis syndromes in such a way that they could be investigated, and ultimately treated, in a more efficacious fashion. These new definitions, while not being radically different from the old criteria, serve the purpose of Read more [...]

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Options for Treatment of Benign Prostatic Hyperplasia: Alpha-Blockers

Posted by admin on June 21st, 2011 No Comments

Benign prostatic hyperplasia is one of the most common benign tumors affecting men over 40 years of age. The mean age at which patients develop symptoms is between 60 to 65 years. Ninety percent of men in their eighties exhibit histologic evidence of disease, 81% will experience symptoms due to benign prostatic hyperplasia, and 10% will develop acute urinary retention. The aging of the population also increases the number of men at risk for benign prostatic hyperplasia. In the past year, more than 1.7 million men have made an office visit to the urologist and these numbers continue to increase. In the last 10 years, there has been a major shift in both the physician's and patient's perception of benign prostatic hyperplasia. From being considered a disease of aging, requiring intervention only to prevent potential complications, an emphasis shift has occurred. Today, benign prostatic hyperplasia is considered more a disease that affects quality of life; therefore, both evaluations and treatments are currently designed to relieve symptoms and reduce side effects. In this context, the use of medical Read more [...]

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Pharmacophysiologic Rationale for the use of Alpha-Blocker Drugs

Posted by admin on June 21st, 2011 No Comments

The prostate gland is often referred to as being composed of five distinct lobes during fetal development — anterior, posterior, median, and two lateral lobes. In the adult prostate, this distinction is usually abolished and the prostate is considered to be composed of three concentric layers: the outer layer (the external prostate gland proper) and the two inner layers (the periurethral glands). Prostate cancer tends to arise in the outer layers of the glands while benign prostatic hyperplasia starts in the inner periurethral glands. Benign prostatic hyperplasia is believed to arise from fibrostromal proliferation in the periurethral glands. As the gland progresses in size, patients will present with lateral and/or median prostatic lobe(s) enlargement. This latter will result in (a) compression, narrowing, and elongation of the prostatic urethra; (b) growth of the median lobe into the bladder, causing a ball-valve effect and possibly an increase in irritative symptoms; (c) a bladder response to obstruction that may result initially in hypertrophy and subsequently in decompensation, stasis Read more [...]

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Long-Acting Antagonists

Posted by admin on June 21st, 2011 No Comments

Terazosin Terazosin, an antihypertensive drug, is a selective alpha-1 adrenergic antagonist that has been studied extensively and is currently approved by the FDA for treatment of benign prostatic hyperplasia. This long-acting agent allows a once-a-day dosing schedule. Lepor and associates published the first randomized, placebo-controlled, phase II trial of terazosin, the largest experience to date with terazosin in the treatment of benign prostatic hyperplasia. This multicenter study included 285 men with symptomatic benign prostatic hyperplasia who were randomly assigned in equal proportions to receive placebo or 2, 5, or 10 mg of terazosin administered once daily. Of the 285 men, 237 patients completed the 4-week, single-blind, placebo lead-in period and the 12-week, double-blind treatment period. All terazosin treatment groups exhibited a significantly greater decrease in total Boyarsky symptom scores compared with the placebo cohort (p < .001). The increase in peak urinary flow rate for the 10 mg group was 3.0 mL per second, a significant change compared to baseline (p < .001). This Read more [...]

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Cardiovascular Effects

Posted by admin on June 21st, 2011 No Comments

By blocking the alpha-1 adrenoceptor, these drugs cause peripheral vasodilation, which reduces total peripheral vascular resistance and thereby lowers high blood pressure. Indeed, reduction in blood pressure was the primary indication for which alpha-1 adrenoceptor antagonists were developed. The effects of selective alpha-1 blockade on the blood pressure of patients with benign prostatic hyperplasia are important in terms of the risk of adverse effects related to hypotension, both in normotensive patients and in those treated with other anti-hypertensives. Given that both benign prostatic hyperplasia and hypertension become more prevalent with increasing age, and that one would expect to find that a large proportion of older men have both conditions, these are very real concerns. Clinicians are often faced with the dilemma of what to do when treating a patient with benign prostatic hyperplasia who already has hypertension controlled by an agent other than alpha-blockers. Should the existing antihypertensive agent be withdrawn or the alpha-blockers be given in addition to existing medication? Read more [...]

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Prevention of the Progression and Long-Term Complications of Benign Prostatic Hyperplasia

Posted by admin on June 21st, 2011 No Comments

Benign prostatic hyperplasia is a common condition in men, second only to cataract surgery as the most common reason for a surgical procedure among elderly men. In 1995, over 5.5 million men in the United States above the age of 50 years were estimated to meet criteria proposed for discussing therapy for benign prostatic hyperplasia according to treatment and diagnostic guidelines. The lifetime risk for medical or surgical intervention for benign prostatic hyperplasia in a 50-year-old man has been estimated at 40%. Benign prostatic hyperplasia represents a significant burden on health care, particularly in light of the aging of the general population. The three components of benign prostatic hyperplasia, namely palpable enlargement of the prostate, lower urinary tract symptoms (lower urinary tract symptoms), and obstruction, overlap to varying degrees in individual patients. Despite the high prevalence of benign prostatic hyperplasia, standard clinical diagnostic criteria are yet to be developed. This limits the ability to characterize the natural history in untreated patients, and to identify Read more [...]

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Pharmacologic Strategies for Prevention

Posted by admin on June 21st, 2011 No Comments

Alpha-Blockers Alpha-adrenergic blockers have been shown to rapidly alleviate symptoms and improve urinary flow rates in men with lower urinary tract symptoms but do not appear to alter the disease process in such a way as to prevent progression. Alpha-blockers may induce apoptosis in the prostate gland but longitudinal data do not show a measurable effect on prostate volume. Alpha-blockers have not been typically studied in long-term controlled trials, and there are therefore only limited data available on long-term effects on outcomes. Only two controlled studies longer than 3 months have reported on outcomes such as acute urinary retention or benign prostatic hyperplasia-related surgery; only one of these, the 1-year placebo-controlled HYCAT study, had a predefined objective of evaluating resource utilization although the high proportion of patients who discontinued the study (42%) and had no follow-up information limits interpretation. In HYCAT, no significant difference was found in the number of patients who underwent prostatectomy during the 1-year trial (48 in the placebo and 41 in the Read more [...]

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Alpha Blockers

Posted by admin on May 10th, 2011 No Comments

Overview Hyperplasia of the stromal tissue may or may not lead to significant enlargement of the prostate, but it usually leads to dynamic benign prostatic hyperplasia by increasing prostatic smooth muscle, which triggers increased smooth-muscle tension and resistance to urine flow. (The dynamic and static components of benign prostatic hyperplasia are discussed in the "Etiology and Pathophysiology" section.) Alpha1-adrenergic receptors in the bladder neck and prostatic capsule mediate tension in these muscles. Although the alpha1-adrenergic antagonists, or alpha blockers, currently used to block these receptors (e.g., doxazosin [Pfizer/AstraZeneca's Cardura/Cardura XL, generics] and terazosin [Abbott's Hytrin, generics]) reduce benign prostatic hyperplasia symptoms and resistance to urine flow, some of them also cause cardiovascular side effects. The latest entrants in this field (e.g., tamsulosin [Astel-las/Boehringer Ingelheim/Abbott's Harnal/Flomax/Omnic, others] and alfuzosin [Sanofi-Aventis's Xatral/Xatral SR/Uroxatral, others]) are prostate-specific or uroselective alpha blockers that reduce Read more [...]

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Finasteride

Posted by admin on May 10th, 2011 No Comments

The search for specific inhibitors of 5-alpha-reductase led to the discovery of finasteride (Merck's Proscar), which has been marketed in the United States and Europe since 1992 and is now the leading agent of this class. Merck licensed finasteride to Yamanouchi and Banyu, a Merck subsidiary, in Japan, but no development has been reported since 1994. Finasteride inhibits dihydrotestosterone synthesis and thereby prevents enlargement of the prostate. It acts predominantly via suppression of the type 2 isoenzyme of 5-alpha-reductase, preventing conversion of testosterone to dihydrotestosterone and reducing serum and prostatic tissue dihydrotestosterone levels by 70% and 85%, respectively. Because 5-ARIs reduce prostate size, the subset of patients with static benign prostatic hyperplasia is most likely to benefit from this type of therapy. The clinical benefits and risks of finasteride treatment are best described by the Proscar Long-Term Efficacy and Safety Study (PLESS). In this four-year, double-blind, placebo-controlled trial, 3,040 men with moderate to severe symptoms of benign prostatic Read more [...]

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