SOPH 411: Pathophysiology and Therapeutics II (BPH) PDF

SOPH 411: PATHOPHYSIOLOGY AND THERAPEUTICS II (BENIGN PROSTATIC HYPERPLASIA – BPH) EBENEZER WIAFE PhD, MPharm, Pharm D, QPPV, ECBA, MPSGH DEPARTMENT OF PHARMACY PRACTICE, SCHOOL OF PHARMACY, UNIVERSITY O...

SOPH 411: PATHOPHYSIOLOGY AND THERAPEUTICS II (BENIGN PROSTATIC HYPERPLASIA – BPH) EBENEZER WIAFE PhD, MPharm, Pharm D, QPPV, ECBA, MPSGH DEPARTMENT OF PHARMACY PRACTICE, SCHOOL OF PHARMACY, UNIVERSITY OF HEALTH AND ALLIED SCIENCES, HO, GH CENTRE OF EXCELLENCE FOR PHARMACOVIGILANCE IN SOUTHERN AFRICA, SCHOOL OF PUBLIC HEALTH, UNIVERSITY OF THE WESTERN CAPE, BELLVILLE, SA DISCIPLINE OF PHARMACEUTICAL SCIENCES, COLLEGE OF HEALTH SCIENCES, UNIVERSITY OF KWAZULU-NATAL, DURBAN, SA EMAIL: [email protected] || TEL.: +233 501364131/249160931  DISCLOSURE STATEMENT I, EBENEZER WIAFE, DECLARE THAT I; HAVE NO CONFLICTS OF INTEREST. DO NOT OWN ANY OF THE IMAGES IN THIS PRESENTATION DOCUMENT. OUTCOMES – A After this engagement, you should be able to: appreciate the epidemiology, aetiology, pathophysiology, signs and symptoms and diagnosis. justify medication choice, set therapeutic objectives/goals and predict outcomes. OUTCOMES – B Identify/solve problems of drug therapy. recommend non-pharmacological therapeutic interventions. identify patient-specific parameters relevant in initiating drug therapy, and monitoring therapy. prepare individualised therapeutic plans  THE PROSTATE - A Walnut-sized gland (about 30 grams). Has 5 lobes: anterior, posterior, 2 lateral and a median. Location: bladder (below), penis (base), rectum (in front), surrounds the urethra (middle). Produces ejaculate (enzymes, zinc and THE PROSTATE - B  DEFINITION AND EPIDEMIOLOGY - A Benign prostatic enlargement (BPE) is extremely common. It has been estimated that about half of all men aged 80 years and over will have lower urinary tract symptoms (LUTS) associated with bladder outlet obstruction (BOO) due to BPE. BPO – benign prostatic obstruction. DEFINITION AND EPIDEMIOLOGY - B Subjected 111 men, 40 – 70 years, to the International Prostate Symptoms Score (IPSS) questionnaire and ultrasonographic imaging of the prostate volume (PV). LUTS prevalence: IPSS  42.3%; IPSS + PV  27.0%. BPE: LN subjects  41.98%; LP  100% DEFINITION AND EPIDEMIOLOGY - C Benign prostatic hyperplasia (BPH) is the histological abnormality that underlies BPE. BPH is nonmalignant growth of the prostate stroma and epithelial glands that causes enlargement of the prostate gland. Microscopic: histologic evidence of  DEFINITION AND EPIDEMIOLOGY - D BPH has also been referred to as; hyperplasia. benign prostatic hypertrophy. adenomatous hypertrophy. glandular hyperplasia. stromal hyperplasia.  AETIOLOGY - A Age: the most well-reported risk factor. Sex Steroid Hormones: ↑serum conc of DHT. Genetics: larger PV and younger age of onset. Metabolic Syndrome (MS): serum C- reactive protein level, a feature of MS, may be associated with intraprostatic  AETIOLOGY - B Cardiovascular Disease: possible pathophysiologic relationship between BPH and hypertension. Diabetes and Alterations in Glucose Homeostasis: ↑PV. Lipids: although conflicting, it is implicated in obesity, MS.  AETIOLOGY - C Sedentary Lifestyle: moderate to vigorous physical activity reduced the risk of BPH by as much as 25% relative to a sedentary lifestyle. Inflammation: linked to the development of BPH and prostate cancer. Race: controversial topic but stronger pieces of evidence exists for prostate  PATHOPHYSIOLOGY - A The development of BPH requires testicular androgens as well as aging. Castrated before puberty/disorders of impaired androgen production/action ≠ BPH. The prostate maintains its ability to respond to androgens throughout life  cell proliferation and differentiation in  PATHOPHYSIOLOGY - B Androgens may actively inhibit cell turnover/death. Androgenic hormone, testosterone (80 – 90% of prostatic testosterone)  active metabolite dihydrotestosterone (DHT) by the enzyme 5α-reductase. Two subtypes of 5α-reductase (type 1 and type 2) have been described.  PATHOPHYSIOLOGY - C In the stromal cell, DHT acts in an autocrine fashion and in a paracrine fashion after diffusing into nearby epithelial cells. The nuclei of prostatic cells are rich in androgen receptors. Prostatic levels of DHT remain high with aging even though peripheral levels of PATHOPHYSIOLOGY - D PATHOPHYSIOLOGY - E  PATHOPHYSIOLOGY - F Prostatic smooth muscle represents a significant proportion of the gland. Smooth muscle cells in the prostate - at the bladder neck and in the prostatic capsule - are richly populated with α- adrenergic receptors. Contraction of the prostate and bladder neck are mediated by α1-adrenergic  PATHOPHYSIOLOGY - G Clinically detectable BPH nodules arise from a variety of adenomas in the transitional and periurethral zones  PROSTATIC CAPSULE.  SYMPTOMS - A Voiding/emptying symptoms; impairment in the size and force of the urinary stream hesitancy and/or straining to void intermittent or interrupted flow sensation of incomplete emptying terminal dribbling.  SYMPTOMS - B Filling/storage symptoms; nocturia daytime frequency urgency urgency incontinence. Emptying/voiding symptoms are the most prevalent, but filling/storage symptoms are  SIGNS Detectable anatomic enlargement of the prostate on physical examination or imaging. Bladder changes secondary to obstruction can occur. Upper tract changes of ureterectasis, hydroureter, and/or hydronephrosis can result.  DIAGNOSIS – A Essentials of diagnosis includes; History digital rectal examination focused physical examinations urinalysis urine cytology in those with significant irritative symptoms  DIAGNOSIS – B serum creatinine renal ultrasound if creatinine is abnormal standardised symptom assessment American Urological Association Symptom Score (AUASS) International Prostate Symptom Score (IPSS)  DIAGNOSIS – C Digital Rectal Exam (DRE) DIAGNOSIS – D DIAGNOSIS – E  DIAGNOSIS – F A  DIAGNOSIS – G B  DIAGNOSIS – H Urodynamics of bladder outlet obstruction Residual urine volume/post-void residual volume (PVR)  50 to 100 mL represents the lower threshold to define abnormal. Uroflowmetry  15 mL/sec – no obstruction; and 10 to 15 mL/sec – equivocal.  INDICATION FOR THERAPY Certain absolute or near-absolute indications exist; refractory or repeated urinary retention related azotemia significant recurrent gross hematuria related recurrent or residual infection a large unreduced residual urine volume  THERAPEUTIC GOALS Most men seek treatment for BPH because of the bothersome nature of their symptoms that affect the quality of their lives. DISCUSS PHARMACOTHERAPY – A PHARMACOTHERAPY – B PHARMACOTHERAPY – C  PHARMACOTHERAPY – D Alpha-adrenergic antagonists: tamsulosin 5-alpha reductase inhibitors: finasteride Combined therapy: finasteride plus tamsulosin Anticholinergic agents (M2 and M3): oxybutynin  MONITORING AND OUTCOMES Symptoms and symptom scores Quality-of-life indices Correction of undesirable sequelae (e.g., azotemia) Urodynamic indices Size (for bulk-reducing therapy) Alteration of natural history  COM. AND ALT. MEDICINE (CAM) Complimentary and alternative medicine (CAM) for the treatment of LUTS generally consists of phytotherapeutic preparations; saw palmetto plant (Serenoa repens) Stinging nettle (Urtica dioica) PROSTACURE TEA NON-PHARMACOLOGICAL THERAPY Minimally invasive; transurethral microwave thermotherapy (TUMT) transurethral needle ablation (TUNA) water vapor thermal therapy prostatic urethral lift (PUL) transurethral electrosurgical incision of the NON-PHARMACOLOGICAL THERAPY Surgical; simple prostatectomy (open or robotic) transurethral resection of the prostate (TURP) holmium laser enucleation of the prostate (HoLEP) thulium laser enucleation of the prostate THERAPEUTIC CONCORDANCE COUNSELLING CLASS DISCUSSION HEALTH PROMOTION COUNSELLING CLASS DISCUSSION  REFERENCES Asare, G. A., Sule, D. S., Oblitey, J. N., Ntiforo, R., Asiedu, B., Amoah, B. Y.,... & Botwe, B. O. (2021). High degree of prostate related LUTS in a prospective cross-sectional community study in Ghana (Mamprobi). Heliyon, 7(11). Russo, G. I., Urzì, D., & Cimino, S. (2018). Epidemiology of LUTS and BPH. In Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia (pp. 1-14). Academic Press. Fode, M., Sønksen, J., McPhee, S. J., & Ohl, D. A. (2010). Chapter 23. Disorders of the male reproductive tract. Pathophysiology of Disease. 6th ed. New York, NY: McGraw-Hill. Guzzo, T. J., Kovell, R. C., Ziemba, J. B., Weiss, D. A., & Wein, A. J. (Eds.). (2023). Penn Clinical Manual of Urology, E-Book. Elsevier