Benign Prostatic Hyperplasia

Archive for the ‘Benign Prostatic Hyperplasia’ Category

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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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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Alpha-1 Adrenoceptor Antagonists

Posted by admin on June 21st, 2011 No Comments

Short-Acting Antagonists Phenoxybenzamine Phenoxybenzamine was the initial alpha-adrenergic blocking drug used for management of benign prostatic hyperplasia; however, it was a nonselective alpha-1 and alpha-2 receptor irreversible antagonist that produced many side effects. It did improve prostatic symptoms but had significant cardiovascular side effects in 30% of patients. It has also been shown to have mutagenic properties in animal studies. This drug is therefore no longer used in managing benign prostatic hyperplasia. Prazosin Prazosin was the next selective alpha-1-blocker used to manage benign prostatic hyperplasia, at which time it was already being used for treating hypertension. Prazosin had fewer side effects and responded better than phenoxybenzamine. This drug, however, did have its setbacks; it was dispensed twice daily, which caused significant first-dose effect and vascular side effects during the morning dosage. In long-term studies, > 32% of patients discontinued use of prazosin due to various adverse effects. Prazosin must be given three times per day to be effective 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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Alpha-1A Subtype Selective Alpha-Adrenergic Antagonist

Posted by admin on June 21st, 2011 No Comments

Tamsulosin Tamsulosin is a newly developed member of this class of drugs, is suitable for once-a-day dosing schedule, and is currently being studied extensively in the treatment of benign prostatic hyperplasia. Tamsulosin is a (-)-S-[2-[[2-(o-ethoxyphenoxy) ethylamino] propyl]-2-methoxybenzenesulfonamide HC1, a sulphamoylphenethylamine derivative which possesses potent and selective alpha-1A receptor antagonism. In preclinical trials, tamsulosin has been shown to have 13 times more efficacy for prostatic smooth muscle as compared to urethral smooth muscles. Other studies have revealed a 10 to 12 times higher affinity for prostatic receptors as opposed to vascular and extraprostatic tissue. Recent changes in nomenclature of alpha-blockers reveal the alpha-1A receptors to predominate in the prostate while alpha-IB and alpha-ID receptors predominate in the vascular smooth muscle. Tamsulosin belongs to a class of alpha-lA-receptor antagonists that have preferred selectivity for prostatic smooth muscle although it does have some binding to vascular smooth muscle receptors as well. Tamsulosin binding 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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Findings from Community Studies and Clinical Trials

Posted by admin on June 21st, 2011 No Comments

Symptoms It is well known that the prevalence of urinary symptoms increases with age. Based on cross-sectional community-based studies, age-related increases in the prevalence of lower urinary tract symptoms have been consistently found in numerous countries in studies using similar questionnaires, despite cross-cultural differences in the prevalence of moderate to severe symptoms. Few longitudinal studies have explored the progression of lower urinary tract symptoms by following untreated men over time. Recent longitudinal findings from the community-based Olmsted County Study of Urinary Symptoms and Health Status Among Men suggest a measurable progression in symptom severity, on average, over 3.5 to 4 years accompanied by high intraindividual variability The age-related changes found in this study were consistent with autopsy prevalence studies relating prostate volume to age. Another community study has also documented symptom progression over 3 years. Continued follow-up of such community-based cohorts of men should better characterize the rate of progression of urinary symptoms over longer Read more [...]

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Long-Term Complications

Posted by admin on June 21st, 2011 No Comments

Untreated, benign prostatic hyperplasia may lead to complications such as acute or chronic urinary retention, renal failure, serious or recurrent urinary tract infections, bladder decompensation, hydronephrosis, and calculi, particularly bladder calculi. Few studies, however, have quantified the long-term risk of these complications. Several authors have reviewed the available literature on the incidence and risk of such complications in detail. Acute Urinary Retention and Associated Risk Factors Bladder outlet obstruction may progress to acute urinary retention, a painful, sudden inability to urinate. Many patients consider this to be the most serious outcome of untreated benign prostatic hyperplasia, and it often requires emergency medical attention. Some clinicians considered acute urinary retention to be an absolute indication for surgical intervention while others have proposed catheterization and a voiding trial.' The recurrence of acute urinary retention within 1 week of catheterization is high, however. The etiology of acute urinary retention is not well understood. Based on previous studies, Read more [...]

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Archive for the ‘Benign Prostatic Hyperplasia’ Category

Symptoms and Treatment

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