BPH

• Watchful waiting (observation)
• Alpha-Adrenergic Antagonists
  • Background:
    • There are at least three a-1 adrenergic receptor subtypes in human tissues that have been identified by pharmacologic studies and receptor cloning.
    • The current nomenclature recognizes a-l_A, a-1B, and a-1_D.
    • All three subtypes have been found in prostatic stromal tissue.
    • The a-1_A receptor comprises 60 to 85 percent of the a-1 population.
  • Potential side effects include orthostatic hypotension (said to occur primarily in patients with hypertension), dizziness, fatigue, nasal stuffiness, and ejaculatory disturbances
  • Agents classified according to:
    • The degree of a-1 receptor selectivity
    • Dosing requirements
      • Determined by serum half life
  • All of the classic a-1 blockers appear to be very similar in terms of clinical efficacy and safety.
  • The maximal response to alpha blockade occurs within 2 weeks of dose escalation
  • Agents:
    • Phenoxybenzamine
      • A nonselective alpha blocker (blocks (a-1 and a-2 receptors)
      • First agent used to treat BPH.
    • Prazosin
      • Relatively selective a-1 blocker
      • Requires 3 times daily dosing
    • Terazosin/doxazosin
      • Relatively selective a-1 blockers
      • Half lives that permit once daily dosing
    • Tamsulosin
      • Superselective blocker for the a-1A subtype
      • Of the three molecularly cloned subtypes of the a-1 receptor, the a-1_A seems responsible for prostate smooth muscle tension
      • Once daily dosing
• 5-a Reductase Inhibitors
  • Finasteride
    • Competitive selective inhibitor of type II 5 a reductase
    • Does not reduce DHT levels to castrate values
    • Reduces prostatic DHT by 80 to 90 percent
    • Does not lower plasma testosterone.
    • Reduces group mean serum PSA levels by approximately 50 percent but the effect on individual levels is highly variable
    • Approximately 12 percent of patients develop sexual side effects including decreased libido (3.4 to 4.7 percent), ejaculatory disorder (2.7 percent), and impotence (1.7 to 3.7 percent).
    • The drug does seem to be effective in the management of BPH-related hematuria.
    • The drug is optimally effective in men with prostate volumes over 40 to 50 mL.
    • Studies:
      • Finasteride reduces prostate volume approximately 20 percent
      • The overall treatment related improvement in symptom score varies from 0.6 units to 2.2 units
      • Peak flow rate improvement ranges from 0.2 to 1.8 mL/sec
  • Dutestaride
    • Blocks Type I and Type II 5 a reductase
    • Similar efficacy and side effect profile to finasteride

Male LUTS

• Therapy to Facilitate Urinary Storage and Bladder Filling
  • Bladder related - inhibiting bladder contractility, decreasing sensory input and/or increasing bladder capacity
    • Anticholinergic agents
    • Musculotropic relaxants
    • Calcium antagonists
    • Potassium channel openers
    • Prostaglandin inhibitors
    • B-Adrenergic agonists
    • a-Adrenergic antagonists
    • Tricyclic antidepressants
    • Dimethylsulfoxide (DMSO)
    • Polysynaptic inhibitors
    • Capsaicin, resiniferatoxin, and similar agents
  • Outlet related
    • a-Adrenergic agonists
    • Tricyclic antidepressants
    • B-Adrenergic antagonists, agonists
  • Therapy to Facilitate Bladder Emptying and Voiding
    • Bladder related (increasing intravesical pressure or facilitating bladder contractility)
      • Parasympathomimetic agents
      • Prostaglandins
      • Blockers of inhibition a-Adrenergic antagonists
      • Opioid antagonists
    • Outlet related (increasing outlet resistance)
    • At a site of anatomic obstruction - Decrease prostate size or tone
      • a-Adrenergic antagonists
      • 5-a Reductase inhibitors
      • LHRH agonists/antagonists
      • Antiandrogens
      • Prostatectomy
      • Prostatotomy (diathermy, heat)
    • At the level of the smooth sphincter
      • a-Adrenergic antagonists
      • B-Adrenergic antagonists
      • At the level of the striated sphincter
      • Skeletal muscle relaxants
      • a-Adrenergic antagonists
      • Botulinum A toxin (injection)

References

• Abrams P: In support of pressure-flow studies for evaluating men with lower urinary tract symptoms. Urology 44:153-155, 1994.
• Ball AJ, Fenely RCL, Abrams PH: The natural history of untreated "prostatism " Br J Urol 53:613-616, 1981.
• Barry MJ: Epidemiology of benign prostatic hyperplasia. AUA Update Series 16:274-279, 1997.
• Barry MJ, Fowler FJ, Bin L, et al: The natural history of patients with benign prostatic hyperplasia as diagnosed by North American urologists. J Urol 157:10-15, 1997.
• Barry MJ, Fowler FJ, Jr., O'Leary MP, and the Measurement Committee of the AUA: The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 148:1549-1557, 1992.
• Barry MJ, Williford WO, Chang Y, et al: Benign prostatic hyperplasia specific health status measures in clinical research: How much change in the AUA symptom index and the BPH impact index is perceptible to patients? J Urol 154:1770-1774, 1995.
• Blaivas J: The bladder is an unreliable witness. Neurourol Urodyn 15:443-445, 1996.
• Denis L, Griffiths K, Khoury S, et al, eds. 4th International Consultation on Benign Prostatic Hyperplasia (BPH). Plymouth, United Kingdom, Plymbridge Distributors, Ltd., 1998.

  Chapter 3: Regulation of prostatic growth. Cockett ATK, Coffey D, DiSant Agnese A, et al.
  Chapter 5: Initial evaluation of LUTS. Artibani W, Correa R, Desgranchamps F, et al.
  Chapter 6: Quantification of symptoms, quality of life and sexuality. Adolfsson J, Barry M, Batista JE, et al.
  Chapter 7: The urodynamics of LUTS. Abrams P, Buzelin JM, Griffiths D, et al.
  Chapter 10: Interventional therapy. Altwein J, Baba S, Blute M, et al. Chapter 11: Endocrine treatment. Akaza H, Bartsch G, Calais daSilva F, et al. Chapter 12: Alpha-blocker therapy. AldoBono V, Andersson KE, Chapple C, et al.
  Chapter 15: BPH 1997-New treatment strategy. ElHilali M, Kirby R, McConnell J.
  Lepor H, Williford WO, Barry MJ, et al: The efficacy of terazosin, finasteride, or both in BPH. N Engl J Med 335:533-539, 1996.

• McConnell J: Why pressure flow studies should be optional and not mandatory for evaluating men with benign prostatic hyperplasia. Urology 44:156-158, 1994.
• McConnell JD, Barry MJ, Bruskewitz R, et al: Benign prostatic hyperplasia: Diagnosis and treatment. Clinical Practice Guideline, no. 8, AHCPR publication No. 94-0582, Rockville, Md., Agency for Health Care Policy Research, Public Health Service, US Dept. Of Health and Human Services, 1994.
• Walsh PC, Retik AB, Vaughan ED Jr., Wein AJ, eds: Campbell's Urology, 7th ed. Philadelphia, Saunders Company, 1998. Chapter 45: The molecular biology, endocrinology, and physiology of the prostate and seminal vesicles. Partin AW, Coffey DS.

  Chapter 46: Epidemiology, etiology, pathophysiology, and diagnosis of benign prostatic hyperplasia. McConnell JD.
  Chapter 47: Natural history, evaluation, and nonsurgical management of benign prostatic hyperplasia. Lepor H.
  Chapter 48: Minimally invasive treatment of benign prostatic hyperplasia. McCullough DL.
  Chapter 49: Transurethral surgery. Mebust WK.

• Wasson JH, Reda DJ, Bruskewitz RC, et al: A comparison of transurethral surgery with watchful waiting for moderate symptoms of BPH. N Engl J Med 332:75-79,1995.
• Wein AJ: Criteria for assessing outcome following intervention for benign prostatic hyperplasia. In: Lepor H, ed. Prostatic Diseases. Philadelpha, Saunders, 1999, pp 210-231.

Please log-in or register in order to submit comments.

Powered by AkoComment!