Prostatic hyperplasia, benign

N-Heterocycles as drugs for the treatment of benign prostatic hyperplasia 97JMC1293. 

Ornithine decarboxylase is a pyridoxal dependent enzyme. In its catalytic cycle, it normally converts ornithine (7) to putrisine by decarboxylation. If it starts the process with eflornithine instead, the key imine anion (11) produced by decarboxylation can either alkylate the enzyme directly by displacement of either fluorine atom or it can eject a fluorine atom to produce viny-logue 12 which can alkylate the enzyme by conjugate addidon. In either case, 13 results in which the active site of the enzyme is alkylated and unable to continue processing substrate. The net result is a downturn in the synthesis of cellular polyamine production and a decrease in growth rate. Eflornithine is described as being useful in the treatment of benign prostatic hyperplasia, as an antiprotozoal or an antineoplastic substance [3,4]. 

TRPV5 and TRPV6, also known as the epithelial Ca2+ channel or ECaC (TRPV5) and Ca2+transporter 1 or Ca2+ transporter-like (TRPV6), are the only two Ca2+-selective TRP channels identified so far. They may function in vitamin D-dependent transcellular transport of Ca2+in kidney, intestine and placenta. TRPV6 is also expressed in pancreatic acinar cells, and in prostate cancer, but not in healthy prostate or in benign prostate hyperplasia. 

Saw palmetto (cabbage palm, fan palm, scrub palm) Serenoa repens %mptoms of benign prostatic hyperplasia Generally well-tolerated occasional gastrointestinal effects May interact with hormones such as oral contraceptive drugs and hormone replacement therapy. 

HABERMANN H, RAY V, HABERMANN w and PRiNS G s (2001) Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer. J Urol 166(6) 2267-72. 

The expression of TRPVl in the bladder is, however, not restricted to afferent nerves urothelium, detrusor muscle and fibroblasts also express TRPVl in the human bladder [140]. The implication of these findings for intravesical vanilloid therapy is unclear [141], but the increase in TRPVl immunoreactivity in the urothelium in patients with neurogenic detrusor overactivity (that occurs in concert with increased TRPVl in bladder af-ferents) is a very intriguing finding [142]. In the male urogenital system, TRPVl is also present in testicles, prostate and scrotal skin [143], and it was postulated that TRPVl ligands may be beneficial in the treatment of benign prostatic hyperplasia [144]. 

Explain the pathophysiologic mechanisms underlying the symptoms and signs of benign prostatic hyperplasia. 

List the desired treatment outcomes for a patient with benign prostatic hyperplasia. 

Compare and contrast a-adrenergic antagonists versus 5a-reductase inhibitors in terms of mechanism of action, treatment outcomes, adverse effects, and interactions when used for management of benign prostatic hyperplasia. 

Formulate appropriate counseling information for patients receiving drug treatment for benign prostatic hyperplasia. 

O The lower urinary tract symptoms and signs of benign prostatic hyperplasia are due to static, dynamic, or detrusor factors. The static factor refers to anatomic obstruction of the bladder neck caused by an enlarged prostate gland. The dynamic factor refers to excessive stimulation of a-adrenergic receptors in the smooth muscle of the prostate, urethra, and bladder neck. The detrusor factor refers to irritability of hypertrophied detrusor muscle as a result of long-standing bladder outlet obstruction. 

Surgical intervention should be reserved for patients with severe lower urinary tract symptoms of benign prostatic hyperplasia or those with complications of disease (such as recurrent urinary tract infections, renal failure, and bladder calculi). 

When monitoring efficacy of drug treatment for benign prostatic hyperplasia, subjective endpoints include relief of obstructive and irritative voiding symptoms. Objective endpoints include improvements of urinary flow rates, decreased post-void residual urinary volume, and decreased complications of disease. 

Enlarged prostate on digital rectal exam check for prostate nodules or induration, which would suggest prostate cancer instead of benign prostatic hyperplasia as the cause of the patient s voiding symptoms... 

Urinalysis to rule out infection as a cause of the patient s voiding symptoms also check urinalysis for microscopic hematuria, which typically accompanies benign prostatic hyperplasia. 

TABLE 49-2. Objective Tests Used to Assess the Size of the Prostate and Complications of Benign Prostatic Hyperplasia (BPH)... 

FIGURE 49-1. Algorithm for selection of treatment of BPH based on symptom severity. (From Lee M. Benign prostatic hyperplasia. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 

AUA, American Urological Association BPH, benign prostatic hyperplasia DRE, digital rectal exam PVR, post-void residual urine volume. 

Chappie CR. Pharmacological therapy of benign prostatic hyperplasia/ lower urinary tract symptoms an overview for the practicing clinician. BJU Int 2004 94 738-744. 

Djavan B, Chappie C, Milani S, Marberger M. State of the art on the efficacy and tolerability of alpha, adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology 2004 64 1081-1088. 

Flanigan RC, Reda DJ, Wasson JHM, et al. 5 year outcome of surgical resection and watchful waiting for men with moderately symptomatic benign prostatic hyperplasia a Department of Veterans Affairs cooperative study. J Urol 1998 160 12-17. 

Larson TR. Current treatment options for benign prostatic hyperplasia and their impact on sexual function. Urology 2003 61 692-698. 

Marberger M, Harkaway R, de la Rosette J. Optimising the medical management of benign prostatic hyperplasia. Eur Urol 2004 45 411-419. 

McConnell JD, Roehrborn CG, Bautista OM et al. The long term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl 1 Med 2003 349 2387-2398. 

Milani S, Djavan B. Lower urinary tract symptoms suggestive of benign prostatic hyperplasia latest update on a, adrenoceptor antagonists. BJU Int 2005 95(Suppl 4) 29—36. 

Unless the sphincter mechanism is compromised by surgery or trauma, SUI is exceedingly rare in males. The most common surgeries predisposing to SUI in males are radical prostatectomy for prostate cancer and transurethral resection of the prostate for benign prostatic hyperplasia. 

Benign prostatic hyperplasia (BPH) is one of the most common problems of elderly men, affecting more than 40% of men over age 70. BPH results in the urinary symptoms of hesitancy and frequency. Since prostate cancer affects a similar age group and often has similar presenting symptoms, the presence of BPH often complicates the diagnosis of prostate cancer, although it does not appear to increase the risk of developing prostate cancer.2,5... 

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