资源描述
Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Alpha,1,-adrenoceptors,and BPH,A.G.Ramage D.Sc.,Department of Pharmacology,University College London,Royal Free Campus,Urinary Symptoms in Men,80,70,60,50,40,30,20,10,0,-49,50-59,60-69,70-79,80-84,Weak Stream,Urgency,Frequency,Nocturia,Homma et al 1994,Prevalence(%),Urinary Symptoms in Women,60,50,30,20,10,0,-49,50-59,60-69,70-79,80-84,Weak Stream,Urgency,Frequency,Nocturia,Homma et al 1994,Prevalence(%),40,Innervation of Lower Urinary Tract,Sympathetic Nerves from T10 to L2,Hypogastric Nerve,PelvicNerve,Pudental,Nerve,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 Sympathetic,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 bladder,urethral resistance,bladder capacity,bladder wall compliance,frequency and amplitude of bladder contractions,mediate by alpha adrenoceptors,Distribution of Alpha,1,-Adrenoceptors,Pelvic Floor,External Sphincter,Internal Sphincter,Trigone,Detrusor,Prostate Gland,Physiological Consequence of,a,-adrenoceptor blockade,FALL IN BLOOD PRESSURE,POSTURAL HYPOTENSION,NASAL STUFFINESS,FAILURE OF EJACTULATION,MIOSIS,Urinary incontinence?,Reflex to BP Fall -Tachycardia,-Sodium&Water retention(Renin),b,1,-adrenoceptor antagonists,Alpha Adrenoceptor Classification,a,-,a,1,and,a,2,adrenoceptors,Observation-phenoxybenzamine caused an increase in the release,of noradrenaline from sympathetic nerves,Phenoxybenzamine,Selective,a,1,-adrenoceptor antagonist,-less postural hypotension,-less tachycardia,Cause Central sympathoinhibition,Available,a,1,adrenoceptor antagonists:-,Prazosin;Doxazosin;Terazosin,Terazosin;Alfuzosin;Tamsulosin,;,Indoramin!,a,1,-adrenoceptor receptors,and the lower urinary tract,Trigone&Sphincter muscles -contraction,a,1,-adrenoceptor can be divided into :-1A,1B and 1D,a,1L,Role 1B unknown really,1A and 1D,Reduces Severity and Bothersomeness of Symptoms,Improvement in Key Urinary Symptoms of BPH with Doxazosin,Urgency*,Nocturia*,Hesitancy*,Weak Stream*,Frequency,p0.5 vs placebo,Adapted from:Chapple CR et al.Br J Urol 1994,Correlation Plots,Human Prostate&,1,Subtypes,10,9,8,7,6,10,9,8,7,6,10,9,8,7,6,6,7,8,9,10,6,7,8,9,10,6,7,8,9,10,pKi,pKi,pKi,Prazosin,Terazosin,Indoramin,SNAP-1069,5-methylurapidil,SK&F104856,RS 17053,A,B,D,Prostate pA,2,Forray et al 1995,Ford et al 1996,Doxazosin,7.0,9.0,8.5,8.0,7.5,In Vivo,Profile,Dox,Ter,Alf,Tam,5-MU,Prostate Pressure,Blood Pressure,Pseudo pA,2,Subtype Selectivity,9.5,9.0,8.5,8.0,7.5,7.0,Dox,Ter,Alf,Tam,5-MU,alpha 1A,alpha 1B,alpha 1D,pKi,Low,Affinity,High,Chon JK et al 1999 J Urol 161(6):2002-8,doxazosin does the same,Effect of Terazosin on Prostate Apoptosis,in Clinical Biopsies,Treatment period in months,The Sympathetic Cascade and the Pathophysiology of Disease,Urethral Resistance,De-Tumescence,Tissue Proliferation,Blood Pressure,Treatment of the Whole PatientA Balancing Act,A,D,B,A,D,B,D,B,A,BP,Lipid Profile,1A?,1B?,1D?,HDL to LDL Ratio,Tissue Proliferation,1A?,1B?,1D?,Anti-proliferative,1A,1B,1D,Blood Pressure Control,1A,1B?,1D?,Symptoms Flow,Balance Is Beneficial,A,D,A,D,B,D,B,A,B,A,A,A,
展开阅读全文