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1、Alpha1-adrenoceptors and BPHA.G.Ramage D.Sc.Department of PharmacologyUniversity College LondonRoyal Free Campus,Urinary Symptoms in Men,80,70,60,50,40,30,20,10,0,-49,50-59,60-69,70-79,80-84,Homma et al 1994,Prevalence(%),Urinary Symptoms in Women,60,50,30,20,10,0,-49,50-59,60-69,70-79,80-84,Homma e
2、t al 1994,Prevalence(%),40,Innervation of Lower Urinary Tract,Sympathetic Nerves from T10 to L2,Hypogastric Nerve,PelvicNerve,PudentalNerve,T10,T11,T12,L1,L2,L3,L4,L5,Parasympathetic and Somatic Nerves from the 2nd,3rd and 4th Sacral Segments,ProstateGland,External Urethral Sphincter,Role of the Sym
3、pathetic,Not essential-for either storage or release-role in the control of bladder capacity and outlet resistance during storage,Sympathetic input to the bladder is tonically active during filling,Surgical or pharmacological blockade of sympathetic pathways to the bladderurethral resistance bladder
4、 capacity bladder wall compliance frequency and amplitude of bladder contractions,mediate by alpha adrenoceptors,Distribution of Alpha1-Adrenoceptors,Pelvic Floor,External Sphincter,Internal Sphincter,Trigone,Detrusor,Prostate Gland,Physiological Consequence of a-adrenoceptor blockade,FALL IN BLOOD
5、PRESSURE POSTURAL HYPOTENSIONNASAL STUFFINESSFAILURE OF EJACTULATIONMIOSISUrinary incontinence?,Reflex to BP Fall-Tachycardia-Sodium&Water retention(Renin),b1-adrenoceptor antagonists,Alpha Adrenoceptor Classification a-a1 and a2 adrenoceptors,Observation-phenoxybenzamine caused an increase in the r
6、eleaseof noradrenaline from sympathetic nerves,Phenoxybenzamine,Selective a1-adrenoceptor antagonist-less postural hypotension-less tachycardia,Cause Central sympathoinhibition,Available a1adrenoceptor antagonists:-Prazosin;Doxazosin;Terazosin Terazosin;Alfuzosin;Tamsulosin;Indoramin!,a1-adrenocepto
7、r receptors and the lower urinary tract,Trigone&Sphincter muscles-contraction,a1-adrenoceptor can be divided into:-1A,1B and 1D,a1L,Role 1B unknown really 1A and 1D,Reduces Severity and Bothersomeness of SymptomsImprovement in Key Urinary Symptoms of BPH with Doxazosin,Urgency*,Nocturia*,Hesitancy*,
8、Weak Stream*,Frequency,p0.5 vs placebo Adapted from:Chapple CR et al.Br J Urol 1994,Correlation Plots,Human Prostate&1 Subtypes,7.0,Low,Affinity,High,Chon JK et al 1999 J Urol 161(6):2002-8doxazosin does the same,Effect of Terazosin on Prostate Apoptosis in Clinical Biopsies,Treatment period in months,The Sympathetic Cascade and the Pathophysiology of Disease,Treatment of the Whole PatientA Balancing Act,BP,Lipid Profile,HDL to LDL Ratio,Tissue Proliferation,Anti-proliferative,Blood Pressure Control,Symptoms Flow,Balance Is Beneficial,A,D,A,D,B,D,B,A,B,A,A,A,
