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1、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,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(%),Uri
2、nary 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 an
3、d 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 d
4、uring 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
5、,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
6、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 sympa
7、thoinhibition,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 rea
8、lly,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
9、,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,S
10、ubtype 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 P
11、athophysiology 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,
Alpha1adrenoceptors and BPH
