Alfuzosin

Posts Tagged ‘Alfuzosin’

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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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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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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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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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 [...]

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Doxazosin

Posted by admin on May 10th, 2011 No Comments

Doxazosin (Pfizer's Cardura/Cardura XL, generics) is a long-acting alpha blocker selective for alpha1-adrenergic receptors; this agent has been used to treat hypertension since 1991. At the end of 2001, a once-daily formulation, Cardura XL (doxazosin GITS [gastrointestinal therapeutic system]), had been launched for benign prostatic hyperplasia and hypertension in 13 countries, including France, Germany, Spain, and the United Kingdom. Pfizer filed for approval of Cardura XL in April 2001 in the United States and was approved in 2005. Although doxazosin is not as selective as some of the newer alpha blockers, it has comparable efficacy and is a good alternative for patients who may have difficulty covering the cost of tamsulosin or alfuzosin. Since publication of Medical Therapy of Prostatic Symptoms (MTOPS), a study of the effects of combination therapy on benign prostatic hyperplasia progression, doxazosin is now implicated as an inhibitor of prostatic development when used in combination with finasteride. The study is described later in this section in conjunction with the 5-ARI finasteride. The Read more [...]

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Terazosin

Posted by admin on May 10th, 2011 No Comments

Terazosin (Abbott's Hytrin, generics) is a long-acting, alpha1-adrenergic-receptor blocker with a prolonged half-life that permits once-daily dosing. Abbott markets terazosin in the United States and several European countries; Mitsubishi-Tokyo Pharmaceuticals is the licensee in Japan. In March 2000, the FDA granted Mylan approval to market its generic version of terazosin; since then, several other generics have launched. The Hytrin Community Assessment Trial (HYCAT), a 12-month, multicenter study, was conducted in the United States to investigate the clinical effectiveness of terazosin therapy. Two thousand and eighty-four patients with AUASI scores greater than 12 (moderate to severe symptoms of benign prostatic hyperplasia) were randomized to terazosin, titrated to 10 mg, or to placebo. For patients unable to tolerate high-dose terazosin,5 mg tablets were administered instead of 10 mg. Periodic assessments during the 12-month treatment period showed a significant difference in AUASI scores between the active treatment group and the placebo group at every follow-up visit. The researchers Read more [...]

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Posted by admin on May 10th, 2011 No Comments

The original formulation of alfuzosin, marketed in Europe since 1997, is a uroselective agent that is taken three times daily. In 2000, Sanofi-Synthelabo (now Sanofi-Aventis) launched a twice-daily, sustained-release formulation of alfuzosin, Xatral SR, in the United Kingdom, Spain, and Germany. A once-daily, controlled-release formulation of alfuzosin — called Xatral OD in the United States and Xatral XL in Europe — was developed using SkyePharma's Geomatrix technology. Xatral XL has been launched in the United Kingdom, France, Italy, and Germany. The initial European approvals triggered a milestone payment to SkyePharma from Sanofi-Aventis; SkyePharma will also receive royalty payments from product sales. In the United States, the FDA approved a new drug application (NDA) for Xatral OD in June 2003, and the agent launched in November 2003. Alfuzosin has been licensed to Astellas Pharma in Japan and is currently undergoing clinical investigation. Alfuzosin's uroselectivity appears to be achieved through preferential distribution in prostate tissue, which allows it to have efficacy and safety Read more [...]

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Posts Tagged ‘Alfuzosin’

Symptoms and Treatment

Drugs. Meds