2011, Number 1
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Rev Cubana Farm 2011; 45 (1)
Pharmacological treatment of the benign prostatic hyperplasia
Pérez GY; Molina CV; Oyarzábal YA; Mas FR
Language: Spanish
References: 49
Page: 109-126
PDF size: 103.05 Kb.
ABSTRACT
Benign prostatic hyperplasia is a common disease in over 50 years-old men
consisting in uncontrolled and benign growth of prostatic gland that leads to lower
urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral
involving the increased conversion of testosterone in dihydrotestosterone by the
prostatic 5α-reductase action, which brought about events that encourage the
prostate growth (static component) and the increase of the bladder and prostate
smooth muscle tone (dynamic component) regulated by the α1 -adrenoceptors
(ADR). The pharmacological treatment of the benign prostatic hyperplasia includes
the prostatic 5α-reductase inhibitors, the α1-adrenoreceptor blockers, their
combined therapy and the phytotherapy. This paper was aimed at presenting the
most relevant aspects of the pharmacology of drugs used for treating the benign
prostatic hyperplasia, and providing elements to analyze their efficacy, safety and
tolerability. To this end, a review was made of the different drugs for the treatment
of this pathology and they were grouped according to their mechanism of action.
Natural products were included as lipid extracts from Serenoa repens and Pygeum
africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved
beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-
004 is a prostatic 5a-reductase inhibitor, an α1-adrenoceptor antagonist, α 5-
lipooxygenase inhibitor and has antioxidant action, all of which reveals a
multifactoral mechanism. The results achieved till now indicate that D-004 is a safe
and well-tolerated product.
REFERENCES
Alcaraz A, Hammerer P, Tubaro A, Schröder FH, Castro R. Is There Evidence of a Relationship between Benign Prostatic Hyperplasia and Prostate Cancer? Findings of a Literature Review. Eur Urol. 2008;55:4-5.
Zhu YS, McGinley JL. 5α-reductase isozymes and androgen actions in the prostate. Ann N Y Acad. Sciences 2009;1155:43-56.
Curtis N. Inflammation and Benign Prostatic Hyperplasia. Urol Clin North Am. 2008;35:109-115(a).
Chéchile GE. Tratamiento con medicamentos. Farmacología del cáncer prostático. Antiandrógenos y análogos de lh-rh. Pros. 2007;4:125-30.
Schwinn DA, Roehrborn CG. α1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008; 15:193-9.
Roehrborn CG. BPH progression: concept and key learning from MTOPS, COMBAT, and ALF-ONE. BJU. 2008;101:17-21 (a).
Tarter TH, Vaughan ED. Inhibitors of 5a-reductase in the treatment of benign prostatic hyperplasia. Curr Pharm. 2006;12:775-83.
Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti L, Ciccariello M, et al. Combination Therapy with Rofecoxib and Finasteride in the Treatment of Men with Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH). Urol Eur. 2003;47:72-9.
Martin-Morales A, Meyer G, Ramirez E. Prevalencia de disfunción eyaculatoria secundaria al tratamiento con alfa-bloqueantes en pacientes con hiperplasia benigna de próstata. Actas Urol Esp. 2008;32:705-12.
Marberger M. Drug insight: 5-alpha-reductase inhibitors for the treatment of benign prostatic hyperplasia. Nat Clin Pract Urol. 2006;3:495-503.
Lam JS, Romas NA, Lowe FC. Long term treatment with finasteride in men with symptomatic benign prostatic hyperplasia. 10 year follow up. Urol. 2003;61:354-7.
Babak R, Pourandarjani R, Habibollahi P, Mualeki A. Finasteride induced depression: a prospective study. BMC Clin Pharmacol. 2006;6:7-10.
Dolder CR. Dutasteride: a dual 5-alpha reductase inhibitor for the treatment of symptomatic benign prostatic hyperplasia. Ann Pharmacother. 2006;40:658-65.
Djavan B. Milani S, Fong YK. Dutasteride novel dual inhibitor of 5alphareductase for benign prostatic hyperplasia. Expert Opin Pharmacother. 2005;6:311-7.
Benjamin ZL, LeBlanc KM, Schoenfeld DA, Eastell R, Finkelstein JS. Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metabol. 2003;80:1002-7.
Benjamin Z, Rohrer L, Stephen D, Gallo J, Longcope Ch. Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels. J Clin Endocrinol Metabol. 2004;89:1174-80.
Marks LS, Mostaghel EA, Nelson PS. Prostate tissue androgens: history and current clinical relevance. Urol. 2008;72:247-54.
Ohbuchi M, Miyata M, Nagai D, Shimada M, Yoshinari K, Yamazoe Y. Role of Enzymatic N-Hydroxylation and Reduction in Flutamide Metabolite-Induced Liver Toxicity. Drug Metab Dispos. 2009;37:97-105.
Wong P, Lawrentschuk N, Bolton DM. Phosphodiesterase 5 inhibitors in the management of benign prostatic hyperplasia and erectile dysfunction: the best of both worlds. Curr Opin Urol. 2009;19:7-12.
Gao W, James T. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Endocrinol. 2007;12:241-8.
Prata TS, Palmiero P,M. Angelillo A, Sbeity Z, De Moraes CG, Liebmann JM, et al. Iris morphologic changes related to α(1)- adrenergic receptor antagonists implications for intraoperative floppy iris syndrome. Ophthalm. 2009;166:877-81.
Bar-Yosef Y, Mabjeesh NJ, Laufer M, Neulander EZ. Kaver I, Matzkin H. Alpha blockers in use for symptomatic benign prostatic hyperplasia-are all drugs born equal? Harefuah. 2008;147:514-74.
Mas M, Gutiérrez PM. Inhibidores de la fosfodiesterasa 5 y tracto urogenital. Rev Int Androl. 2007;1:73-81.
Roehrborn CG. Tadalafil administrado una vez al día para síntomas del tracto urinario inferior secundario a hiperplasia benigna de próstata: un estudio de determinación de dosis. J Urol. 2008;180:12-5 (b).
Kevin T, Mc Vary. Review of combination therapy in patients with benign prostatic hyperplasia. Clin Therapeutics. 2007;29:387-98.
Minnery CH, Getzenberg RH. Benign prostatic hyperplasia cell line viability and modulation of JM-27 by doxazosin and ibuprofen. J Urol. 2005;174:375-9.
Kaplan SA, González RR, Ogiste J, Te AE. Combination of adrenergic alpha blocker, alfuzosin and 5-PDE inhibitor, sildenafil citrate is superior to monotherapy in treating lower urinary tract symptoms (LUTS) and sexual dysfunction. Urol. 2006;175:528-32.
WHO. Monographs on Selected. Med Plants. 2007;3(11).
Koch E. Extracts from fruits of Saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms. Plant Med. 2001;67:489-500.
Odenthal KP. Phytotherapy of benign prostatic hyperplasia (BPH) with Cucurbita, Hypoxis, Pygeum, Urtica and Sabal serrulata (Serenoa repens). Phytother Res. 1996;10(Suppl.1):S141-S143.
Rhodes CW, Priomka RL, Berman C, Vergult G, Gabriel M, Pierre-Malice M, et al. Comparison of finasteride (Proscar), a 5 alpha reductase inhibitor, and various commercial plant extracts in vitro and in vivo 5 alpha reductase inhibition. Prost. 1993;20:43-51.
Chapkin RS, Davidson LA, Weeks BR, Lupton JR, McMurray DN. Immunomodulatory Effects of (n-3) Fatty Acids: Putative Link to Inflammation and Colon Cancer. J Nutr. 2007;137:200S-204S.
Bent S, Kane C, Shinohara K. Saw Palmetto for Benign Prostatic Hyperplasia. NEJM. 2006;354: 557-66.
Arruzazabala ML, Molina V, Más R, Carbajal D. Effects of D-004, tamsulosin and the combined therapy D004 plus tamsulosin on urodynamic changes induced with phenylephrine in rats. Arznettel-Forsch. Drug Res. 2008;58:81-5.
Pérez Y, Menéndez R, Más R, Gonzáles RM. Plasma levels, tissue distribution, and excretion of radioactivity after single dose administration of (3H)-oleic acid added to D-004, a lipid extract of the fruit of Roystonea regia, in rats. Curr Ther Res. 2006;67:406-19 (a).
Chevalier G, Benard P, Cousse H, Bengone T. Distribution study of radioactivity in rats after oral administration of the lipido/sterolic extract of Serenoa repens (Permixon) supplemented with (1-14C)-lauric acid, (1-14C)-olleic acid or (1-14C)- beta-sitosterol. Eur J Drug Metab Pharmacokinet. 1997;22:73-83.
Gámez R, Mas R, Noa M, Menéndez R, García H, Rodríguez Y, et al. Oral acute and subchronic toxicity of D-004, a lipid extract from Roystonea regia fruits, in rats. Drugs Exp Clin Res. 2005;31:101-8.
Gutiérrez A, Gámez R, Noa M, Mas R, Pardo B, Valle M, et al. Mendoza N. and García H. Evaluation of D-004 effects in the uterotrophic assay in mature ovariectomized rats. Lat Am J Pharm. 2008;27:710-5.
Carbajal D, Arruzazabala ML, Mas R, Molina V, Rodriguez E, Gonzalez V. Effect of D-004, a lipid extract from Cuban royal palm fruit, on inhibiting prostate hyperplasia induced with testosterone and dihydrotestosterone in rats. Curr Ther Res Clin Exptl. 2004;65:505-14.
Pérez Y, Menéndez R, Mas R, González RM. In vitro effect of D-004, a lipid extract from the Cuban Royal palm (Roystonea regia), on of prostate steroid 5-α reductase activity. Curr Ther Res Clin Exptl. 2006;67:396-405 (b).
Pérez Y, Menéndez R, Mas R, González RM. Efecto in vitro del D-004, extracto lipídico de los frutos de la palma real, sobre receptores androgénicos de tejido prostático. Rev CNIC Cien Biol. 2007;38:177-99.
Arruzazabala ML, Mas R, Molina V, Noa M, Carbajal D. Effect of D-004, a lipid extract from the fruits of Cuban royal palm, on the atypical prostate hyperplasia induced with phenylephrine in rats. Drug R & D. 2006; 7:233-24.
Menéndez R, Carbajal D, Mas, Pérez Y, Molina V, Arruzazabala ML, et al. Efecto del D-004, extracto lipídico de los frutos de la palma real (Roystonea regia) sobre el granuloma inducido por algodón en ratas y sobre la lipooxigenasa presente en leucocitos polimorfonucleares. Lat J Pharm. 2006;25:213-8.
Noa M, Arruzazabala ML, Carbajal D, Más R, Molina V. Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats. Int J Tiss React. 2005;27:193-8.
Menéndez R, Más R, Pérez Y, González RM. In vitro effect of D-004, a lipid extract of the ground fruits of the Cuban royal palm (Roystonea regia), on rat microsomal lipid peroxidation. Phytother Res. 2007;21:89-95.
Pérez Y, Molina V, Mas R, Menéndez R, González RM, Oyarzábal A, et al. Ex vivo antioxidant effects of D-004, a lipid extract from Roystonea regia fruits, on rat prostate tissue. Asian J Androl. 2008;10:659-66.
Pérez Y, Oyarzábal A, Molina V, Jiménez S, Cuverco D, Mas R. Estudio del D- 004 sobre la defensa antioxidante endógena en ratas con hiperplasia inducida por inyección de testosterona. Rev Cubana Farm 2010; 66 (2). Disponible en: http://bvs.sld.cu/revistas/far/vol_44_2_10/far11210.htm
Lopez E, Molina V, Illnait J, Oyarzábal A, Fernández L, Más R, et al. Antioxidant effects of D-004, a lipid extract from the Roystonea regia fruits, on the plasma of healthy men. Asian J Androl. 2007;11:385-92.
López E, Illnait J, Ramírez Y, Fernández L, Más R, Gámez R, et al. Estudio fase I de la tolerabilidad del D-004, un extracto lipídico del fruto de la palma real (320- 960 mg/d) en voluntarios sanos. Rev CNIC Cienc Biol. 2008;7:33-43.