Benign Prostatic Hyperplasia: Pathogenesis and Medications Aging -> Increased Testosterone -> Testosterone metabolized into DHT by type II 5-a-reductase in prostate -> DHT binds to androgen receptor in prostate cell nuclei -> Hyperplasia of the prostate -> Prostate encapsulated by fibromuscular tissue, therefore grows inwards -> Prostatic urethral compression and bladder outlet obstruction -> Increased Bladder pressures -> Bladder smooth-muscle hyperplasia (detrusor thickening) -> Increased Sensitivity (i.e. overactive detrusor) -> Decreased Volume to first detrusor contractio -> LUTS - alpha-1 blockers (e.g. tamsulosin) -> Bladder and prostate smooth-muscle alpha-1 receptor antagonism Relaxation of bladder outlet and prostate smooth-muscle -> Improved urinary outflow - PDE-5 inhibitors (e.g. tadalafil) -> Decr PDE-5-mediated cGMP degradation in prostate smooth-muscle and associated vascular supply -> Relaxation of prostate smooth-muscle -> Improved urinary outflow - 5-ARIs (e.g. dutasteride) -> Decr 5-a-reductase activity -> Decr Conversion of testosterone into DHT -> Decr Progression of LUTS - LHRH receptor antagonists (e.g. cetrorelix) -> GnRH antagonism -> Decr LH secretion from pituitary -> Decr Testosterone secretion from testicular Leydig cells -> Decr DHT production -> Decr progression of LUTS - ß3-adrenergic agonists (e.g. mirabegron) -> Relaxation of detrusor muscle -> Incr Bladder capacity -> Improved LUTS - anticholinergics (e.g. oxybutynin) -> Acetylcholine antagonism at muscarinic receptors -> Relaxation of bladder outlet smooth-muscle -> Incr volume to first detrusor contraction -> Improved LUTS - NSAlDs -> Decr COX activity -> Decr Prostaglandin release -> Analgesia and Decreased Prostatic inflammation #BPH #Benign #Prostatic #Hyperplasia #Prostate #Pathophysiology #Medications #Pharmacology #Urology
