Alpha-adrenoceptor antagonists (α-blockers) are efficacious in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), also termed symptomatic benign prostatic hyperplasia (BPH), causing bladder outlet obstruction (BOO). There is little difference among the various α-blockers in terms of efficacy in treating LUTS. However, conventional quinazoline derivatives such as terazosin, doxazosin and alfuzosin, originally developed for hypertension, have inherent cardiovascular extension effects, which influence the well being and safety of patients with LUTS by impairing physiological blood pressure (BP) control, even when their effect on unchallenged BP may be quite low. Preclinically, tamsulosin, a sulphonamide-substituted phenethylamine, has a relative selectivity for the α1-adrenoceptors of the lower urinary tract. Clinically, this is associated with fewer cardiovascular extension effects with tamsulosin (modified release capsule) 0.4 mg once daily. This allows the use of convenient regimens of 0.4 mg tamsulosin administered once daily after breakfast from initiation of treatment without the need for ‘step-up’ increases of dose to avoid ‘first-dose’ hypotension. Extensive investigation, including multiple orthostatic stress testing (which otherwise is unusual in the characterization of α-blockers because of their inherent safety), confirms that tamsulosin 0.4 mg definitely carries a lower risk of impaired BP control.

Keywords:
Tamsulosin, Terazosin, Doxazosin, Alfuzosin, Orthostatic hypotension, Benign prostatic obstruction, Lower urinary tract symptoms
1.
Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, Hamburger RJ, Fye C, Lakshman R, Gottdiener J et al: Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. New Engl J Med 1993;328:914–921.
2.
Guyton AC, Montani JP, Hall JE, Davis Manning R Jr: Computer models for designing hypertension experiments and studying concepts. Am J Med Sci 1988;295:320–326.
3.
Awan NA, Needham KE, Evenson MK, Amsterdam EE, Mason DT: Therapeutic application of prazosin in chronic refractory congestive heart failure. Tolerance and ‘tachyphylaxis’ in perspective. Am J Med 1981;71:153–160.
4.
Donnelly R, Elliott HL, Meredith PA, Reid JL: Concentration-effect relationships and individual responses to doxazosin in essential hypertension. Br J Clin Pharmacol 1989;28:517–526.
5.
Donnelly R, Meredith PA, Elliott HL: Pharmacokinetic-pharmacodynamic relationships of alpha-adrenoceptor antagonists. Clin Pharmacokinet 1989;17:264–274.
6.
Grimm RH Jr: Treating hypertension and cardiovascular risk: are there trade-offs? Am Heart J 1990;119:729–732.
7.
Nash DT: Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. Clin Cardiol 1990;13:764–772.
8.
Carruthers SG: Adverse effects of alpha 1-adrenergic blocking drugs. Drug Saf 1994;11:12–20.
9.
de Mey C, Breithaupt K, Schloos J, Neugebauer G, Palm D and Belz GG: Dose-effect and pharmacokinetic-pharmacodynamic relationships of the β1-adrenoceptor blocking properties of various doses of carvedilol in healthy man. Clin Pharmacol Ther 1994;55:329–337.
10.
de Mey C, Enterling D: Assessment of the hemodynamic response to single passive upright tilt by non-invasive methods in normotensive subjects. Meth Fund Exptl Clin Pharmacol 1986;8:449–457.
11.
Eckberg DL: Parasympathetic cardiovascular control in human disease: a critical review of methods and results. Am J Physiol 1980;239: H581–H593.
12.
Glick G, Braunwald E: Relative roles of the sympathetic and parasympathetic nervous systems in the reflex control of heart rate. Circ Res 1965;16:363–375.
13.
Marin Neto JA, Gallo L, Manco JC, Rassi A, Amorim DS: Mechanisms of tachycardia on standing: studies in normal individuals and in chronic Chagas’ heart patients. Cardiovasc Res 1980;14:541–550.
14.
Epstein SE: The role of the capacity and resistance vessels in vasovagal syncope. Circulation 1968;37:524–533.
15.
Glick G, Yu PN: Hemodynamic changes during spontaneous vasovagal reactions. Am J Med 1963;34:342–351.
16.
Mets TF: Drug-induced orthostatic hypotension in older patients. Drugs Aging 1995;6:219–228.
17.
Patel A, Maloney A, Damato AN: On the frequency and reproducibility of orthostatic blood pressure changes in healthy community-dwelling elderly during 60-degree head-up tilt. Am Heart J 1993;126:184–188.
18.
Tilvis RS, Hakala SM, Valvanne J, Erkinjuntti T: Postural hypotension and dizziness in a general aged population: a four-year follow-up of the Helsinki Aging Study. J Am Geriatr Soc 1996;44:809–814.
19.
Shannon RP, Maher KA, Santinga JT, Royal HD, Wei JY: Comparison of differences in the hemodynamic response to passive postural stress in healthy subjects greater than 70 years and less than 30 years of age. Am J Cardiol 1991;67:1110–1116.
20.
Poller U, Medelka G, Radke J, Pönicke K, Brodde O-E. Age-dependent changes in cardiac muscarinic receptor function in healthy volunteers. J Am Coll Cardiol 1997;29:187–193.
21.
King MB, Tinetti ME: A multifactorial approach to reducing injurious falls. Clin Geriatr Med 1996;12:745–759.
22.
Jonsson PV, Lipsitz LA, Kelley M, Koestner J: Hypotensive responses to common daily activities in institutionalized elderly. A potential risk for recurrent falls. Arch Intern Med 1990;150:1518–1524.
23.
Cummings SR, Nevitt MC: Falls. N Engl J Med 1994;331:872–873.
24.
Stewart RB, Moore MT, May FE, Marks RG, Hale WE: Nocturia: a risk factor for falls in the elderly. J Am Geriatr Soc 1992;40:1217–1220.
25.
Allander E, Gullberg B, Johnell O, Kanis JA, Ranstam J, Elffors L and the MEDOS Study Group: Falls and hip fracture. A reasonable basis for possibilities for prevention? Some preliminary data from the MEDOS study. Scan J Rheumatol 1996;25(suppl 3):49–52.
26.
Cummings SR, Nevitt MC, Kidd S: Forgetting falls. The limited accuracy of recall of falls in the elderly. J Am Geriatr Soc 1988;36:613–616.
27.
Avorn J: Including elderly people in clinical trials. Better information could improve the effectiveness and safety of drug use. Br Med J 1997;315:1033–1034.
28.
Coffey DS: Controversies in the management of lower urinary tract symptoms: an overview. Br J Urol 1998;81(suppl 1):1–5.
29.
de Mey C, Enterling D: Variant responses impair the usefulness of passive upright tilt in drug research. Meth and Find Exptl Clin Pharmacol 1988;10:57–64.
30.
Chapple CR: Pharmacotherapy for benign prostatic hyperplasian-rule the potential for alpha1-adrenoceptor subtype–specific blockade. Br J Urol 1998;81(suppl 1):34–47.
31.
Wilde Ml, Fitton A, Sorkin EM: Terazosin: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs Aging 1993;3:258–277.
32.
Fulton B, Wagstaff AJ, Sorkin EM: Doxazosin: an update on its clinical pharmacology and therapeutic applications in hypertension and benign prostatic hyperplasia. Drugs 1995;49:295–320.
33.
Wilde MI, Fitton A, McTavish D: Alfuzosin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs 1993;45(3):410–429.
34.
Sega R, Marazi ME, Bombelli M, Vulpis V, Antonacci A, Leto di Priolo S, Pirrelli A, Libretti A: Comparison of the new alpha-1 blocker alfuzosin with propranolol as first-line therapy in hypertension. Pharmacol Res 1991;24:41–52.
35.
Leto di Priolo S, Priore P, Cocco G, Sfrisi C, Cazor JL: Dose titration study of alfuzosin, a new alpha-1-adrenoceptor blocker, in essential hypertension. Eur J Clin Pharmacol 1988;35:25–30.
36.
Fawzy A, Braun K, Lewis GP, Gaffney M, Ice K, Dias N: Doxazosin in the treatment of benign prostatic hyperplasia in normotensive patients: a multicenter study. J Urol 1995;154:105–109.
37.
Lepor H, Auerbach S, Puraz-Baez A, Narayan P, Soloway M, Lowe F, Moon T, Leifer G, Madsen P: A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. J Urol 1992;148:1467–1474.
38.
Roehrborn CG, Oesterling JE, Auerbach S, Kaplan SA, Lloyd LK, Milam DF, Padley RJ: The Hytrin community assessment trial study: a one-year study of terazosin versus placebo in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). Urology 1996;47:159–168.
39.
Brawer MK, Adams G, Epstein H: Terazosin in the treatment of benign prostatic hyperplasia. Terazosin Benign Prostatic Hyperplasia Study Group. Arch Fam Med 1993;2:929–935.
40.
Lepor H, Kaplan SA, Klimberg I, Mobley DF, Fawzy A, Gaffney M, Ice K, Dias N: Doxazosin for benign prostatic hyperplasia: long-term efficacy and safety in hypertensive and normotensive patients. The Multicenter Study Group. J Urol 1997;157:525–530.
41.
Itskovitz HD: Alpha-1-blockade for the treatment of hypertension: a megastudy of terazosin in 2214 clinical practice settings. Clin Ther 1994;16:490–504.
42.
Hytrin® Prescribing Information, Abbott Laboratories, North Chicago, IL 60064, USA, October 1996.
43.
Lefevre-Borg F: Alfuzosin, a selective alpha-1-adrenoceptor antagonist in the lower urinary tract. Br J Pharmacol 1993;109:1282–1289.
44.
Buzelin JM, Herbert M, Blondin P, the Prazalf Group: Alpha blocking treatment with alfuzosin in symptomatic benign prostatic hyperplasia: comparative study with prazosin. Br J Urol 1993;72:922–927.
45.
Jardin A, Bensadoun H, Delauche-Cavallier MC, Attali P, the BPH-ALF-Group: Alfuzosin for treatment of benign prostatic hypertropy. Lancet 1991;337:1457–1461.
46.
Jardin A, Bensadoun H, Delauche-Cavallier MC, Attali P, the BPH-ALF-Group: Long term treatment of benign prostatic hypertrophy with alfuzosin: a 12–18 month assessment. Br J Urol 1993;72:615–620.
47.
Jardin A, Bensadoun H, Delauche–Cavallier MC, Stalla Bourdillon A, Attali P, the BPH-ALF-Group: Long term treatment of benign prostatic hyperplasia with alfuzosin: a 24–30 month survey. Br J Urol 1994;74:579–584.
48.
Lukacs B, Blondin P, MacCarthy C, Du Boys B, Grippon P, Lassale C: Safety profile of 3 months’ therapy with alfuzosin in 13,389 patients suffering from benign prostatic hypertrophy. Eur Urol 1996;29:29–35.
49.
Buzelin JM, Roth S, Geffriaud-Ricouard C, Delauche-Cavallier MC and the ALGEBI Study Group: Efficacy and safety of sustained release alfuzosin 5 mg in patients with benign prostatic hyperplasia. Eur Urol 1997;31:190–198.
50.
Buzelin JM, Delauche-Cavallier MC, Roth S, Geffriaud-Ricouard C, Santoni JP: Clinical uroselectivity: evidence from patients treated with slow-release alfuzosin for symptomatic benign prostatic obstruction. Br J Urol 1997;79:898–904.
51.
Honda K, Nakagawa C: Alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 in rabbit lower urinary tract and prostate. J Pharmacol Exp Ther 1986;239:512–516.
52.
Honda K, Nakagawa C, Terai M: Further studies on (+/–)-YM-12617, a potent and selective alpha1-adrenoceptor antagonist, and its individual optical enantiomers. Naunyn Schmiedebergs Arch Pharmacol 1987; 336:295–302.
53.
Yamada S, Ashizawa N, Ushijima H, Nakayama K, Hayashi E, Honda K: Alpha1-adrenoceptors in human prostate: characterization and alteration in benign prostatic hypertrophy. J Pharmacol Exp Ther 1987;242:326–330.
54.
Wilde MI, McTavish D: Tamsulosin: A review of its pharmacological properties and therapeutic potential in the management of symptomatic benign prostatic hyperplasia. Drugs 1996;52:883–898.
55.
Soeshi Y, Kobori M, Kobayashi S, Higuchi S, Arima H, Sullivan HR, et al: Absorption, distribution and excretion of 14C-tamsulosin hydrochloride in rats and dogs. Pharmacometrics 1990;40:101–109.
56.
Ohkura T, Yamada S, Matsushita M, Tanaka C, Deguchi Y, Kimura R et al: In vivo measurements of alpha-1- adrenoceptors (ADR) in rats by [3H]-tamsulosin (TAM), Jpn J Pharmacol 1995;67(suppl 1):217P(abstract P2–208).
57.
Flomax® Prescribing Information. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA, 1997.
58.
Chapple CR: α-Adrenergic blocking drugs in bladder outflow obstruction: what potential has α1-adrenoceptor selectivity? Br J Urol 1995;76(suppl 1):47–55.
59.
Michel MC, Buscher R, Kerker J, Kraneis H, Erdbrugger W, Brodde O-E: α1-Adrenoceptor subtype affinities of drugs for the treatment of prostatic hypertrophy. Evidence for heterogeneity of chloroethylclonidine-resistant rat renal α1-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol 1993;348:385–395.
60.
Foglar R, Shibata K, Horie K, Hirasawa A, Tsujimoto G: Use of recombinant α1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophy. Eur J Pharmacol (Mol Pharmacol Sect) 1995;288:201–207.
61.
Michel MC, Grübbel B, Taguchi K, Verfürth F, Otto T, Kröpfl D: Drugs for treatment of benign prostatic hyperplasia: Affinity comparison at cloned alpha-1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol 1996;16(1):21–28.
62.
Richardson CD, Donatucci CF, Page SO, Wilson KH, Schwinn DA: Pharmacology of tamsulosin: saturation-binding isotherms and competition analysis using cloned α1-adrenergic receptor subtypes. The Prostate 1997;33:55–59.
63.
Han C, Hollinger S, Theroux TL, Esbenshade TA, Minneman KP: 3H-Tamsulosin binding to cloned α1-adrenergic receptor subtypes stably expressed in human embryonic kidney 293 cells: antagonist potencies and sensitivity to inactivation by alkylating agents. Pharmacol Commun 1995;5(2):117–126.
64.
Lepor H, Tang R, Shapiro E: The alpha-adrenoceptor subtype mediating the tension of human prostatic smooth muscle. Prostate 1993;22:301–307.
65.
Testa R, Guarneri L, Ibba M, Strada G, Poggesi E, Taddei C, Simonazzi I, Leonardi A: Characterization of α1- adrenoceptor subtypes in prostate and prostatic urethra of rat, rabbit, dog, and man. Eur J Pharmacol 1993;249:307–315.
66.
Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, Gluchowski C: The α1-adrenergic receptor that mediate smooth muscle contraction in human prostate has the pharmacological properties of the cloned human α1C-subtype. Mol Pharmacol 1994;45:703–708.
67.
Chess-Williams R, Chapple CR, Verfürth F, Noble AJ, Couldwell CJ, Michel MC: The effects of SB 216469, an antagonist which discriminates between the α1A-adrenoceptor and the human prostatic α1-adrenoceptor. Br J Pharmacol 1996;119:1093–1100.
68.
Ford APDW, Arredono NF, Blue DR, Bonhaus DW, Jasper JR, Kava MS, Lesnick J, Pfister JR, Shieh IA, Vimont RL, Williams TJ, McNeal JE, Stamey TA, Clarke DE: RS-17053 (N-[2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-α,α-dimethyl-1H-indole-3-ethanamine hydrochloride), a selective α1A-adrenoceptor antagonist, displays low affinity for functional α1A-adrenoceptors in human prostate: implications for adrenoceptor classification. Mol Pharmacol 1996;49:209–215.
69.
Marshall I, Burt RP, Chapple CR: Noradrenaline contractions of human prostate mediated by α1A-(α1C-) adrenoceptor subtype. Br J Pharmacol 1995;115:781–786.
70.
Yamada S, Suzuki M, Tanaka C, Mori R, Kimura R, Inagaki O, Honda K, Asano M, Takenaka T, Kawabe K: Comparative study on alpha-1-adrenoceptor antagonist binding in human prostate and aorta. Clin Exp Pharmacol Physiol 1994;21(5):405–411.
71.
Sitzler G, Heiberl B, Lucker PW, Palm D: Bioequivalence of two atenolol formulations in healthy volunteers. Evaluation and prediction of effect kinetics at β-adrenoceptors in vivo by means of radioreceptor assay. Methods Find Exp Clin Pharmacol 1991;13:129–137.
72.
Harada K, Ohmori M, Fujimura A: Comparison of the antagonistic activity of tamsulosin and doxazosin at vascular alpha1-adrenoceptors in humans. Naunyn Schmiedeberg’s Arch Pharmacol 1996;354:557–561.
73.
Michel MC, Schäfers RF, Fokuhl B, Wasmuth A, Schumacher H: Comparison of hemodynamic effects of tamsulosin (tam) and terazosin (ter) in man. J Urol 1997;157(suppl 4):137 (A537).
74.
Kenny BA, Read AM, Naylor AM, Greengrass PM, Carter AJ, Wyllie MG: Effect of alpha-1-adrenoceptor antagonists on prostatic pressure and blood pressure in the anesthetized dog. Urol 1994;44:52–56.
75.
Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1-adrenoceptor antagonists. J Pharmacol Exp Ther 1997;282:228–235.
76.
Chapple CR: Editorial comment. Br J Urol 1997;79:904–906.
77.
Abrams P, Speakman M, Stott M, Arkell D, Pocock R: A dose-ranging study of the efficacy and safety of tamsulosin, the first prostate-selective alpha-1A-adrenoceptor antagonist in patients with benign prostatic obstruction (symptomatic benign prostatic hyperplasia). Br J Urol 1997;80:587–596.
78.
Chapple CR, Wyndaele JJ, Nordling J, Boeminghaus F, Ypma AFGVM, Abrams P on behalf of the European Tamsulosin Study Group: Tamsulosin, the first prostate-selective alpha-1A-adrenoceptor antagonist. Eur Urol 1996;29:155–167.
79.
Chapple CR, Baert L, Thind P, Höfner K, Khoe GSS, Spångberg A, on behalf of the European Tamsulosin Study Group: Tamsulosin 0.4 mg once daily: tolerability in older and younger patients with lower urinary tract symptoms suggestive of benign prostatic obstruction (symptomatic BPH). Eur Urol 1997;32:462–470.
80.
Buzelin JM, Fonteyne E, Kontturi M, Witjes WPJ, Khan A: Comparison of tamsulosin with alfuzosin in the treatment of patients with lower urinary tract symptoms suggestive of bladder outlet obstruction (symptomatic benign prostatic hyperplasia). Br J Urol 1997;80:597–605.
81.
de Mey C, Michel M C, McEwen J, Moreland T: A double-blind comparison of terazosin and tamsulosin on their differential effects on ambulatory blood pressure and nocturnal orthostatic stress testing. Eur Urol 1998;33:481–488.
82.
Lee E, Lee C: Clinical comparison of selective and non-selective alpha-1A-adrenoceptor antagonists in benign prostatic hyperplasia: studies on tamsulosin in a fixed dose and terazosin in increasing doses. Br J Urol 1997;80:606–611.
83.
Lepor H: Phase III multicenter, placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Urol 1998;51:892–900.
84.
Editorial comment. Alpha adrenoceptor antagonists. Br J Urol 1997; 80
85.
Starkey LP, Trenga C, Miyazawa Y, Ito Y: Lack of clinical interaction effects between tamsulosin and enalapril. Clin Pharmacol Ther 1995;57(2):166 (abstr. PII-11).
86.
Starkey LP, Yasukawa K, Trenga C, Miyazawa Y, Ito Y: Study of possible pharmacodynamic interaction between tamsulosin and nifedipine in subjects with essential hypertension. J Clin Pharmacol 1994;34(10):1019 (abstr 45).
87.
Lowe FC: Coadministration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect. Clin Ther 1997;19:730–742.
1998
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