BPH and ED Treatment: Alpha Blockers, 5-alpha Reductase Inhibitors - PDF

Benign prosta-c Hyperplasia (BPH): enlargement of prostate gland (symptoms or not) Risk increases with age. Sta'c: increased sizeà blockage of flow Androgen derived Dynamic: increased smooth muscle contrac-on Excessive alpha-adrenergic tone Staging: BPHà BPEàBPO Treatmen...

Benign prosta-c Hyperplasia (BPH): enlargement of prostate gland (symptoms or not) Risk increases with age. Sta'c: increased sizeà blockage of flow Androgen derived Dynamic: increased smooth muscle contrac-on Excessive alpha-adrenergic tone Staging: BPHà BPEàBPO Treatment op-ons 1. Alpha-1 antagoniststamsl.sc 2. 5 alpha reductase inhibitors (helps reduce complica-ons)finess 3. PDE5is tm 4. An-cholinergics on 5. B3 agonists 6. Surgery (mod to severe BPO) Key factors contribu-ng to BPH 1. Age > 40 years Birth: pea size 1gà puberty(15-20g by age 25-30)àage > leads to BPE 2. S-mulatory effect of androgens Testosteroneà converted by 5 alpha reductase à DHT DHT will promote prostate growth & stability (key for most) 3. Increased alpha-adrenergic tone in prostate & urethra Alpha 1A adrenergic receptors s-mulated by NE 4. Chronic inflamma-on Poten-al triggers (Dyslipidemia Low serum testosterone Hypoestrogenism) approach to treatment goals: symptom control, prevent disease progression & complica-ons, delay need for surgery AUA symptom score (>3 point decrease) Increase in peak urinary flow rate Normaliza-on of PVR to 40g or PSA > 1.4ng/mL Preferred for enlarged prostates (> 40g) Reduce the risk of disease progression and complica-ons Can be used as combo w/ #1 blockers for faster symptoms relief. MOA inhibit conversion of testosterone to DHT à ↓prostate growth Reduces intrapros-c DHT by 80-90% ↓prostate size & risk of acute urinary reten-on, ↑urinary flow rate, DHT suppression: o finasteride: targets type II enzyme (prostate predominant) § chemopreven-on o Dutasteride : targets type I & II enzymes (broader suppression) § Chemopreven-on ADEs Rarer: gynecomas-a, depression, dizziness & rash. Can also cause persistent sexual dysfucniton Decreased libido erec-le dysfunc-on ejaculatory disorders Contraindica-ons Precau-ons Pregnancy à teratogenic effect on male fetus Avoid having pregnant pa-ents handling. PSA monitoring for prostate cancer risk ADME onset of ac-on/ symptom improvement in 6-12months Max effects seen @ 12months. Long term use (4-6 years) needed for sustained benefit. Monitoring ↓ PSA by 50 % aeer 6-12monthhs Adjustment: double PSA for accurate prostate cancer screening get baseline PSA & DRE before star-ng repeat at 6 months and annually 5 alpha reductase inhibitors Medchem TC an--BPH agent MOA stops DHT conversion CC 4-azasteroids  An'cholinergics/ An'muscarinics Darifenacin, festoterodine, oxybutynin, solifenacin, tolterodine, trospium Indica-ons Overac've bladder (OAB) w/urgency, frequency, urge incon-nence Urge urinary incon-nence (z) Neurogenic detrusor overac-vity MOA: block muscarinic receptors(M2,3) Bladder effects: increases bladder capacity, decreases urgency/incon'nence M3: reduces bladder contrac-ons. M2: affects heart rate~ minor role in bladder ADEs + precau-ons Contraindica'ons Common ADEs Serious ADEs Narrow-angle glaucoma Dry mouth (sugar free gum/water) Cogni-ve decline in elderly Urinary reten-on Cons-pa-on (fiber rich diet/ac-vity) QT prolonga-on Gastric reten-on Blurred vision Acute urinary reten-on Severe GI mo-lity issues Dizziness Dosing: Adults: -trate prn Older adults: use w/cau-on, slow -trate to avoid CNS effects Renal/hepa'c impairment: will need needed ADME : has transdermal Extended release/ DR to minimize Side effects (Oxybutynin crosses BBB)/ Trospium (doesn’t cross BBB) Receptors interac-ons: compe--ve Antagonist of muscarinic receptors Dose response rela-onship: dose dependent reduc'on in bladder contrac-ons & ADEs Peak effect will take weeks to occur An'cholinergic Medchem SAR will mimic acetylcholine. 2nd gen are more uroselec-ve. Ades- SLUDGE TC An--OAB agents PC muscarinic cholinergic receptor antagonists CC amino alcohol esters5 Beta 3-adrenergic agonists Mirabegron (Myrbetriq) & Vibegron (Gemtesa) Indica-ons (can be combo w/an-muscarinics for enhanced efficacy ) Overac-ve Bladder (OAB) urgency, frequency urge incon-nence alterna-ve to An-cholinergics  MOA agonism of beta3 receptors in bladderàincrease cAMPàrelax àenhance bladder storage Reduces irriitving voiding symptoms Increases bladder capacity & interval between voiding Will take 4-8 weeks for efficacy ADME Mirabegron (myrbetriq): plasma concentra-on:3.5hrs. Half-life: 50hrs 25mgà 50mg maintenance Contraindica-ons: severe uncontrolled HTN. Cau-on: HF, cardiomyopathy, older adults (> 80years) Avoid in severe hepa-c impairment ESRD ADEs: QT-prolonga-on (rare) Hypotension (monitor BP @ home) Headache UTI Medchem of beta-3 agonists TC an--OAB agents PC/MOA adrenergic receptor agonists CC artlethanolaminesdd Vibegron (Gemtesa): plasma concentra-on:1-3.5hrs. Half-life: 30hrs 75mg once daily (tablets can be crushed if needed) Contraindica-ons & precau-ons: fewer CV precau-ons ADEs mild fewer CV than Mirabegron Surgery: TURP Vascular system & erec'on Nitric oxide pathway: Achà NO releaseà cGMP produc-onà ↓intracellular Ca2+à smooth muscle relax. cAMP pathway Ach/ prostaglandin E à cAMP produc-onà ↓intracellular Ca2+àsmooth muscle relax. Nervous system psychogenic s'muli Neural pathways Hypothalamic role Efferent nerve pathways Reflexogenic erec'ons: mediated by sacral Dopamine: pro- erectogenic Sympathe'c: inhibitory reflex arc Alpha2-adrenergic s'mula'on Parasympathe'c: Pro-erectogenic Psychogenic erec'ons: ini-ated via CNS Maintains flaccidity Soma'c: pro-erectogenic processing of sensory s-muli  ED: persistent/ recurrent failure to achieve or maintain erec-on for sa-difactory intercourse LASTING: > 3 months Medical condi'ons: HTN, arteriosclerosis, DLD, DM, metabolic syndrome, psychiatric disorders Penile arteries affected earlier than coronary or caro-d arteries. DM: autonomic neuropathy Psychogenic: Mental health factors, age Medica'ons: diure-cs, other chronic diseases An-cholinergic, Dopamine, estrogen, CNS depressants & 5-ARi. Types of ED: Diagnos'cs evalua'ons for ED: Organic ED: vascular, neurologic or hormonal Severity of ED (interna-onal index of erec-le func-on) Psychogenic ED: poor response to sexual s-muli Medical, psychological, surgical history (med condi-ons) Review of current meds () Cardiac reserve assessment Select lab test (4hrs Intracavernosal: no more than 3 -mes per week Intraurethral: no more than 2 doses per day