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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 [...]

Posted in Benign Prostatic Hyperplasia

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 [...]

Posted in Benign Prostatic Hyperplasia

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 [...]

Posted in Benign Prostatic Hyperplasia

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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Silodosin

Posted by admin on May 10th, 2011 No Comments

Among the drugs in the pipeline for benign prostatic hyperplasia, silodosin (Figure 10), also known as KMD-3213, is in the most advanced stage of development. The agent is being codeveloped by Kissei and Daiichi in Japan. In June 2004, a new drug application (NDA) was submitted to the Pharmaceuticals and Medical Devices Agency (PMDA), and in 2004, Daiichi announced an expected launch date of 2006 in Japan. In April 2004, Kissei entered a licensing agreement with Watson Pharmaceuticals, which will develop and market silodosin in Mexico, Canada, and the United States, where Phase III clinical trials were in progress in 2005. In December 2004, Kissei granted Recordati exclusive rights to the development of silodosin in 45 countries in Europe. Silodosin is a highly selective, twice-daily oral alpha blocker that preferentially inhibits the activity of alpha1A-adrenergic receptors, which are predominantly located in the prostate. Other alpha blockers that are considered uroselective, such as tamsulosin, block not only alphai A-adrenoceptors but also other adrenergic receptor subtypes found in Read more [...]

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Benign Prostatic Hyperplasia: Alpha Blockers

Posted by admin on May 10th, 2011 No Comments

Overview Numerous alpha blockers have been approved for the treatment of benign prostatic hyperplasia in the major pharmaceutical markets (United States, France, Germany, Italy, Spain, United Kingdom, and Japan), largely replacing the need for surgical treatment in the past ten years. Alpha blockers, with tamsulosin as the leading agent, currently constitute the largest segment of the benign prostatic hyperplasia drug market. Alpha-blocker drugs may differ in terms of their relative inhibitory potency and specificity for alpha1-adrenergic receptors, but most seem to exhibit the same degree of efficacy in benign prostatic hyperplasia patients . However, the propensity for inducing side effects, such as orthostatic hypotension and retrograde ejaculation, often distinguishes one alpha blocker from another. Nevertheless, alpha-blocker activity is sustained over several years of therapy, thereby eliminating the need for dose increases that could increase side effects. Mechanism Of Action Alpha blockers inhibit the activity of adrenergic receptors (also known as adrenoceptors), which cause smooth-muscle Read more [...]

Posted in Benign Prostatic Hyperplasia

Tamsulosin

Posted by admin on May 10th, 2011 No Comments

Tamsulosin (Astellas/Boehringer Ingelheim/Abbott's Harnal/Flomax/Omnic), the leading alpha blocker, is a long-acting alpha blocker that is selective for alpha1A- and alpha1A-adrenoceptors found predominantly in the prostate. Astellas (formerly Yamanouchi) initially marketed tamsulosin in an immediate-release formulation (Harnal) in Japan and Europe. Boehringer Ingelheim also markets tamsulosin in the United States as a delayed-release formulation (Flomax) to provide more consistent drug levels after each dose. In 1999, Abbott entered an agreement with Boehringer Ingelheim to comarket Flomax in the United States. Tamsulosin selectively binds to alpha1A- and alpha1D-adrenergic receptors, thereby blocking activation by norepinephrine. This highly selective drug reduces the incidence of adverse events because it does not affect alpha ib -adrenoceptors located in blood vessels, spleen, or lungs to a significant extent. Tamsulosin's efficacy is only marginally better than that of other alpha blockers, but it offers a superior side-effect profile. In a 13-week, parallel-design, double-blind Read more [...]

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Benign Prostatic Hyperplasia:Current Therapies

Posted by admin on May 10th, 2011 No Comments

Treatment of benign prostatic hyperplasia (benign prostatic hyperplasia) is directed primarily toward managing symptoms and improving patients' quality of life (QoL). The two dominating classes of pharmacological agents used to treat benign prostatic hyperplasia are alpha Mockers and 5-alpha-reductase inhibitors (5-ARIs). Both drug classes are effective in alleviating lower urinary tract symptoms (lower urinary tract symptoms ) associated with benign prostatic hyperplasia, thereby improving patients' comfort level. Alpha blockers are most useful in alleviating symptoms related to dynamic benign prostatic hyperplasia; 5-ARIs are used for the treatment of static benign prostatic hyperplasia. The dynamic and static forms of benign prostatic hyperplasia are discussed in the "Etiology and Pathophysiology" section. Alpha blockers work by relaxing prostatic muscle involved in dynamic benign prostatic hyperplasia; they cannot stop further growth of the prostate. 5-ARIs and gonadotropin modulators (used only in Japan) reduce the cellular growth seen in static benign prostatic hyperplasia. lower Read more [...]

Posted in Benign Prostatic Hyperplasia

Posts Tagged ‘Prazosin’

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