ࡱ> jlcdefghi@ -Pbjbj "Tuuc$88t :vh9j9j9j9j9j9j9$;R=9999h9h906\8 0T6|890 :7\>F>0\8>\8 0" &99Pharmacotherapy of ____Benign Prostatic Hyperplasia_______________ Barry VanDenHeuvel, PharmD Candidate 2007 Epidemiology The prevalence of histopathologic BPH is age dependant. BPH is very rare in men younger than 50 By 60 years of age, its prevalence is greater than 50%, by the age of 85; its prevalence is as high as 90%. About one half of men who have a histological diagnosis have moderate to severe lower urinary tract symptoms (LUTS) BPH accounts for more than 400,000 hospital stays each year. In 2000, approximately 4.5 million visits to physicians offices were made for a primary diagnosis of BPH, and nearly 8 million doctor visits were made with either a primary or secondary diagnosis of BPH. BPH is an expensive disease, with treatments costing more than $4 billion USD per year. As the male population ages, the cost of BPH is expected to increase even further. BPH costs $1.1 billion annually in direct expenditures for medical services provided at hospital inpatient and outpatient settings, emergency departments, and physicians offices. Disease State Definition Benign prostatic hyperplasia is defined histologically as a disease process characterized by stromal and epithelial cell hyperplasia beginning in the periurethral zone of the prostate The chief complaint of the patient with BPH is usually bothersome LUTS typified by urinary frequency, urgency, nocturia, decreased and intermittent force of stream and the sensation of incomplete bladder emptying. The relationship between BPH and LUTS is complex, however, because not all men with histological evidence of BPH will develop LUTS. In addition, LUTS are neither specific to nor exclusive of BPH; other conditions in the lower urinary tract and elsewhere may be causative. Moreover, not all patients with BPH and LUTS will have prostate enlargement, and prostate enlargement may exist in the absence of LUTS. Patho-physiology While the precise pathophysiologic mechanisms that cause BPH remain unclear, the role of intraprostatic DHT and type II 5a-reductase in the development of BPH is evidenced by several observations: BPH does not develop in men who are castrated before puberty. Castration causes an enlarged prostate to shrink. Patients with type II 5a-reductase enzyme deficiency do not develop BPH. Administration of testosterone to orchiectomized dogs of advanced age produces BPH. The pathogenesis of BPH is often described as resulting from both static and dynamic factors. Static factors relate to anatomic enlargement of the prostate gland, which produces a physical block at the bladder neck and thereby obstructs urinary outflow. Dynamic factors relate to excessive a-adrenergic tone of the stromal component of the prostate gland, bladder neck, and posterior urethra, which results in contraction of the prostate gland around the urethra and narrowing of the urethral lumen. Symptoms of BPH disease may result from static and/or dynamic factors, and this must be recognized when drug therapy is considered. Clinical Presentation General Patient is in no acute distress unless he has severe complications of BPH Symptoms Urinary frequency, urgency, intermittency, nocturia, decreased force of stream, hesitancy, and straining. Signs Digital rectal examination reveals an enlarged prostate (>20g). Laboratory Tests Increased BUN and serum creatinine, elevated PSA. Other Diagnostic Tests Increased AUA Symptoms Score and decreased urinary flow rate (<10 ml/s), and increased postvoid residual urine volume. Risk Factors Age the risk of BPH increases with age, beginning at about age 45 Ethnic background the risk of BPH begins to rise in African-American men about five years earlier than it does for white American men. This condition is less common among men living in Asian countries. Gender male sex. BPH does not occur in women.Diagnosis LUTS is not always associated with BPH and can be caused by other disease states. Nonprostatic causes of symptoms can be excluded in a significant number of patients on the basis of a medical history, physical examination, and urinalysis. 1. In the initial evaluation of all patients presenting with LUTS suggestive of BPH a medical history should be taken to identify other causes of voiding dysfunction or comorbidities that may complicate treatment. The medical history should focus on the urinary tract, previous surgeries, medical conditions and family history. A voiding diary can be very helpful. 2. A physical examination, including both a digital rectal examination (DRE) and a focused neurologic examination, should be performed. The presence of locally advanced prostate cancer, which also can produce LUTS, should be excluded by DRE. 3. A urinalysis should be performed by dipstick testing or microscopic examination of the sediment to screen for hematuria and urinary tract infection (UTI). Bladder cancer, carcinoma in situ of the bladder, UTIs, urethral strictures, distal urethral stones, and bladder stones can produce LUTS in aging men. Although hematuria or pyuria is not universally present in these conditions, a normal urine examination makes these diagnoses less likely. Measurement of the serum prostate-specific antigen (PSA) should be offered to the following patients: 1. Those with at least a 10-year life expectancy and for whom knowledge of the presence of prostate cancer would change management; or 2. Those for whom the PSA measurement may change the management of their voiding symptoms. Baseline renal insufficiency appears to be no more common in men with BPH than in men of the same age group in the general population. The AUA Symptom Index (identical to the seven symptom questions of the International Prostate Symptom Score [IPSS]) should be used as the symptom-scoring instrument in the initial assessment of each patient presenting with BPH. Most patients who seek treatment for BPH do so because symptoms alter quality of life. This will help to determine how bothersome the patient finds that symptoms and will help to develop a therapeutic plan. Following the initial evaluation of the patient, urinary flow-rate recording and measurement of postvoid residual urine (PVR) may be appropriate. These tests usually are not necessary prior to the institution of watchful waiting or medical therapy. However, they may be helpful in patients with a complex medical history (e.g., neurologic or other diseases known to affect bladder function or prior failure of BPH therapy) and inthose desiring invasive therapy. Desired Therapeutic Outcomes* *Reference of Guidelines Used The primary therapeutic outcome of BPH therapy is restoration of adequate urinary flow without adverse effects. As a disease in which therapy is directed at those symptoms the patient finds most bothersome, assessment of outcomes likewise depends on how the patient perceives the effectiveness and acceptability of therapy. The use of a validated, standardized instrument, such as the AUA Symptom Index, for assessing patient quality of life is important in this process. Guidelines: American Urological Association Clinical Guidelines, Management of BPH.Treatment Options** (Non-drug and Drug Therapy include all therapeutic classes/agents available and preferences per treatment guidelines) **See Treatment Options Table Patients with only mild symptoms or moderate to severe symptoms that are not bothersome generally will not benefit from therapy because these symptoms do not significantly impact quality of life. In addition, the risks of medical therapy outweigh the benefits of symptom improvement in this group of men. For these patients, watchful waiting is recommended. Treatment options for patients with moderate to severe symptoms of BPH Watchful Waiting Includes yearly monitoring, education, and lifestyle modifications Medical Therapies- only considered interim measures that only delay complication and the need for surgery. Alpha-adrenergic blockers Alfuzosin, Doxazosin, Tamsulosin, Terazosin 5 Alpha-reductase inhibitors Dutasteride, Finasteride Combination therapy (alpha blocker and 5 alphareductase inhibitor) Minimally Invasive Therapies Transurethral microwave heat treatments CoreTherm"!, Prostatron, Targis, TherMatrx"!* Transurethral needle ablation UroLume stent Surgical Therapies Transurethral resection of the prostate Transurethral electrovaporization Transurethral incision of the prostate Transurethral holmium laser resection/enucleation Transurethral laser vaporization Transurethral laser coagulation (e.g., visual laser ablation) Open prostatectomy. Monitoring (Efficacy and Toxicity Parameters) Efficacy Validated Survey Tool Score, eg. AUA Symptom Index Score Digital Rectal Exam Urinary Flow Rate Postvoid Residual Urine Volume Chem 7: BUN, serum creatnine Toxicity Erectile dysfunction (all) Nausea, abdominal pain, asthenia, dizziness, flatulence, headache, rash, muscle weakness, and gynocomastia. (5a-reductase inhibitors) Orthostatic hypotension, dizziness, tiredness, ejaculatory problems, and nasal congestion. (alpha blockers) UTI, bleeding, infection, hematuria, urinary retention, incontinence, erectile or ejaculatory problems. (major or minor surgical procedures.)  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