- Email: [email protected]
Phentolamine in Erectile Dysfunction: A Comparative Study of Short‐Term Efficacy and Side‐Effects
Blackwell Science, LtdOxford, UKJSMJournal of Sexual Medicine1743-6095Journal of Sexual Medicine 2005200521117120Original ArticleIntracavernous SNP in EDShamloul et al.
117
Intracavernous Sodium Nitroprusside (SNP) versus Papaverine/ Phentolamine in Erectile Dysfunction: A Comparative Study of Short-Term Efficacy and Side-Effects Rany Shamloul, MD,*† Ahmed Atteya, MD,* Abdelrahman Elnashaar, MD,* Amr Gadallah, MD,* Wael Zohdy, MD,* and Wael Abdelsalam, MD* *Department of Andrology Sexology and STDs, Cairo University, Cairo, Egypt; †Department of Physiology, University of Saskatchewan, Saskatoon, Canada ABSTRACT
Objective. The aim of our work is to evaluate the efficacy of intracavernous sodium nitroprusside (SNP) in management of erectile dysfunction (ED) in a clinical comparative study with papaverine/ phentolamine in ED patients. Methods. The study included 40 patients with ED divided into two groups. Group I include 20 patients receiving intracavernous (30 mg papaverine + 1 mg phentolamine) followed 1 week later by intracavernous 300 mg SNP. Group II included 20 patients receiving the same regimen of group I but with intracavernous SNP first followed by papaverine/phentolamine 1 week later. All patients were assessed clinically for their response and any developing complications. Results. The numbers of good and poor responders were not statistically significant (P > 0.05) among the two groups. The mean erectile duration of SNP was similar to bimix (P > 0.05). No side-effects whether local or systemic occurred with SNP while priapism and local penile pain were recorded with bimix solution. Conclusions. Intracavernous pharmacotherapy is still a reliable method both for diagnosis and for treatment of ED. While preliminary results of our study show a potential of SNP to be an effective and safe intracavernous agent, long-term self-injection clinical trials are needed before large-scale usage is recommended. Key Words. Sodium Nitroprusside; Impotence; Intracavernous Drugs
Introduction
E
rectile dysfunction (ED) is defined as the persistent inability to obtain or to maintain penile erection sufficient for satisfactory relations [1]. Intracavernous injection of vasoactive drugs is recognized as an important measure both to diagnose and as a second-line treatment of ED [2]. Many intracavernous vasoactive drugs are used effectively such as papaverine, phentolamine, prostaglandin E1, and their mixtures yet, with considerable side-effects. Short-term undesired effects include priapism and penile pain, while long-term side-effects include cavernous fibrosis [3].
In vivo and in vitro studies suggest that nonadrenergic, noncholinergic relaxation of cavernous smooth muscle is mediated by nitric oxide through activation of the guanosine monophosphate pathway [4]. Sodium nitroprusside (SNP) can result in a dose-dependent increase in cyclic guanosine monophosphate (cGMP) in smooth muscle leading to penile erection [5]. In a recent study Quiang et al. concluded that SNP facilitates relaxation of the penile smooth muscle and penile erection without significant side-effects [6]. The aim of our work is to evaluate the efficacy of intracavernous injection of SNP in management of ED in a clinical comparative study with a bimix J Sex Med 2005; 2: 117–120
118 solution (papaverine + phentolamine) patients.
Shamloul et al. in
ED
Materials and Methods
Two groups were included in this study incorporating 40 patients complaining of ED for more than 1 year and candidates for intracavernous selfinjection program. Twenty-seven patients had previously diagnosed vasculogenic ED, 10 patients had psychogenic ED, and three patients had neurogenic ED. The mean duration of ED was 1.8 ± 0.5 years. The mean age of all patients was 43.5 ± 4.3 years. Detailed history-taking, physical examination including general and local genital examination was performed. All patients had previous unsatisfactory trials of new oral therapies for ED. Group I included 20 patients given an intracavernous 1 mL bimix solution containing 30 mg papaverine + 1 mg phentolamine followed 1 week later by another intracavernous dose of 300 mg SNP. Group II included 20 patients given a single intracavernous dose of 300 mg SNP followed 1 week later by an intracavernous 1 mL bimix solution containing 30 mg papaverine + 1 mg phentolamine. Doses injected of the bimix solution and SNP were previously reported in similar studies [6,7]. Sodium nitroprusside was prepared by dissolving 50 mg of the drug in 2–3 mL of glucose 5%. The concentrated solution was further diluted in 163.5 mL of glucose 5% to provide a solution containing 300 mg SNP per mL. The solution was protected from light and used within 6 hours of preparation. Written informed consents were obtained from all subjects prior to the study. Patients and participating physicians were blinded regarding the nature of the injected drugs.
Technique of Intracavernous Injection All patients underwent an office session of intracavernous injection of the vasoactive substance
injected into the lateral corpus cavernosum through a 30 g needle fixed on a tuberculin syringe. Before injection, a tight rubber band was placed, by a physician, at the base of the penis and left for 2–3 minutes after injection to avoid rapid dispersal of the drug into the systemic circulation. All patients were shown how to apply the rubber band and none of them reported inconvenience. Evaluation of the response was graded according classification of Gerstenberg and associates [8]. Grade 0 was no response postinjection. Grade 1 was minimal tumescence and no rigidity. Grade 2 was moderate tumescence and minimal rigidity. Grade 3 was full tumescence and moderate rigidity. Grade 4 was moderate rigidity but penis could be bent. Grade 5 was full erection. Grades 4 and 5 are sufficient for penetration. Pulse and blood pressure were measured 15 minutes prior and at 15, 30, 60, and 120 minutes following drug administration both in the sitting and standing positions. Any occurring side-effects were recorded and managed accordingly. Priapism (a state of prolonged engorgement or erection of the penis not related to sexual desire or stimulation lasting for 6 hours or more) was treated by repeated aspiration of blood combined with irrigation of saline and intracavernous injection of asypathomimetics (e.g., ephedrine) with careful monitoring of blood pressure. All injections were performed by the same physician, while another physician assessed the grade of erection.
Statistical Analysis Statistical analysis of data was performed using SPSS statistics software for Windows. Pearson chi-square test was used to compare quantitative variables among different classification groups. Results
Table 1 illustrates comparison between intracavernous bimix and SNP regarding erectile duration, side-effects, and efficacy. There was no statistical
Table 1 Comparison between intracavernous bimix and sodium nitroprusside (SNP) as regarding erectile duration, sideeffects, and efficacy
Mean erectile duration (SD) (N = 36) Priapism Penile pain Patients with good response (E4 and E5) Patients with poor response (E2 and E3) * P > 0.05.
J Sex Med 2005; 2: 117–120
Bimix
SNP
48.1 ± 3.8 minutes (4/40) patients 10% (3/40) patients 7.5% (11/40) patients 27.5% (29/40) patients 72.5%
43 ± 2.4 minutes* 0 patients 0 patients (12/40) patients 30%* (28/40) patients 70%
119
Intracavernous SNP in ED Table 2
Blood pressure (BP) changes before and after sodium nitroprusside (SNP) injection
Blood pressure
Before SNP injection
15 minutes after SNP injection
30 minutes after SNP injection
1 hour after SNP injection
2 hours after SNP injection
Systolic BP (mm Hg) Diastolic BP (mm Hg)
117 ± 1.5* 84 ± 1.1
116 ± 2.1 82 ± 1.9
115 ± 1.8 80 ± 2.4
114 ± 3.3 80 ± 2.3
117 ± 1.8 83 ± 2.6
Values are mean ± SD.
significance (P > 0.05) between good and poor responders were not among the two groups. The mean erectile duration regarding bimix was 48.1 ± 3.8 minutes while the mean erectile duration of SNP was 43 ± 2.4 minutes showing no statistical significance (P > 0.05). Table 2 illustrates the blood pressure measurements of all patients before and after intracavernous SNP injection. No significant decrease in blood pressure was noted before and after SNP injection. None of the patients who tried intracavernous SNP experienced prolonged erection while four patients (10%) on bimix solution complained of priapism (three patients with vasculogenic impotence and one with psychogenic impotence). Detumescence was achieved in all patients with priapism following aspiration/irrigation and asypathomimetics injection. Localized penile pain in the form of burning sensation occurred in three cases (7.5%) receiving bimix, while patients receiving SNP did not report this side-effect. No significant changes in blood pressure were recorded after the intracavernous injection of SNP or bimix solution. Discussion
Despite the recent breakthroughs in the development of effective oral treatment of ED, intracavernous pharmacotherapy is still considered by many authors as an effective treatment of ED [9]. Recent reports have demonstrated that in addition to the well-known intracavernous drugs as papaverine, phentolamine, PGE1, and their combinations, newer nitric oxide donor drugs as SNP showed satisfactory response [6]. Nitric oxide generated in response to nonadrenergic and noncholinergic stimulation is the main event leading to vascular smooth muscle relaxation through activation of soluble guanylate cyclase [10]. Nitric oxide also inhibits platelet aggregation and adhesion to endothelial surfaces preventing thrombosis of stagnant blood in sinusoidal spaces during erection [11]. Sodium nitroprusside is commonly used as an antihypertensive agent. It causes an increase in the
intracellular concentration of cGMP) and induces relaxation by activating cGMP-dependent protein kinase, which inactivates the light chain myosin kinase and decreases cytosolic calcium concentration [12]. Several animal studies were conducted to assess the effect of nitric oxide donors on the corpus cavernosum smooth muscles, reporting that nitric oxide activates the synthesis of cGMP and that cGMP causes cavernous smooth muscle relaxation [13–15]. Alprostadil (PGE1) is the most widely used intracavernous drug worldwide. In 1995, Martinez-Pineiro and colleagues reported satisfactory preliminary results of intracavernous SNP in comparison to PGE1 [7]. In Egypt, intracavernous bimix (papaverine + phentolamine), due to its relatively economic price, is used in a large scale to treat ED. This encouraged us to study the efficacy of intracavernous SNP in comparison to the wellestablished bimix solution. In our study there was no significant difference in erectile response among good responders in both groups giving SNP an apparently equal efficacy to bimix solution 30% vs. 27.5%. While these results are similar to that previously reported, our results show a longer erectile duration after intracavernous injection of SNP (43 minutes compared to 24 minutes) [6]. We believe that this may be due to the sufficient time the rubber band was left at the base of the penis, preventing rapid dispersal of SNP to the systemic circulation. Also longer erectile duration renders intracavernous SNP suitable for both diagnosis and treatment of ED. On the other hand the low efficacy of bimix solution in our study may be related to the etiology of ED. Brock and colleagues previously reported severe hypotension with high doses of intracavernous SNP (1,000 mg) which refrained them from continuing their study [16]. Penile pain occurred in the form of burning sensation in 3 (7.5%) out of 40 patients using bimix solution. Previous reports suggested that this may be related to the acidity of the injected solution [17]. Neither local (priapism and penile pain) nor systemic (dizziness, palpitation, and blood pressure changes) sideeffects occurred using SNP. This was also in J Sex Med 2005; 2: 117–120
120 agreement with the results reported previously which advised the use of intracavernous SNP in patients experiencing postinjection penile pain and priapism [18]. We believe that the lack of hypotension in our study may be attributed to the application of the constriction ring during injection and to the use of relatively small dose of SNP. Similar results were previously reported acknowledging that effects of nitric oxide donors on systemic blood pressure were prevented by digital compression at the base of the penis during injection limiting access of the drugs to the systemic circulation [19].
Shamloul et al.
7
8 9
Conclusions
10
Intracavernous pharmacotherapy is still a reliable method for both diagnosis and treatment of ED. While preliminary results of our study show a potential of SNP to be an effective and safe intracavernous agent, long-term self-injection clinical trials are needed before large-scale usage is recommended.
11
Corresponding Author: Rany Shamloul, MD, Department of Andrology Sexology and STDs, Cairo University, Cairo, Egypt. Tel: 1-306-9666619; Fax: 1-306-9666532; E-mail: [email protected]
12
13
References
1 NIH consensus statement on impotence. Int J Impo Res 1993;5:181–7. 2 Ishii N, Watanabe H, Irisawa C, Kikuchi Y, Kubota Y, Kawamura S, Suzuki K, Chiba R, Tokiwa M, Sbirai M. Intracavernous injection of PGE1 for the treatment of erectile impotence. J Urol 1989;141: 323–5. 3 Padma-Nathan H. Minimally invasive therapy for erectile dysfunction: Intracavernosal, oral, transdermal/transglandular and intraurethral approaches. In: Mulchahy JJ, editor. Topics in clinical urology: Diagnosis and management of male sexual dysfunction. NY: Igaku-Shoin; 1997:182–95. 4 Kim N, Azadzoi KM, Goldstein I, de Tejada S. A nitric oxide-like factor mediates nonadrenergic noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991;88: 112–8. 5 Jeremy JY, Ballard SA, Naylor AM, Miller MA, Angelini GD. Effects of sildenafil, a type 5-cGMP phoshpodiesterase inhibitor on cGMP and cAMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 1997;79:958–63. 6 Quiang FU, Yao DH, Jiang YQ. A clinical comparative study on effects of intracavernous injection of J Sex Med 2005; 2: 117–120
14
15
16 17
18
19
sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients. Asian J Androl 2000;2:301–3. Martinez-Pineiro L, Lopez-Tello J, Alonso Dorrego JM, Cisneros J, Cuervo E, Martinez-Pineiro JA. Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. J Urol 1995;153:1487–90. Gerstenberg TC, Nordling J, Hald T, Wagner G. Standardized evaluation of erectile dysfunction in 95 consecutive patients. J Urol 1989;141:857. Montorsi F, Salonia A, Pompa P, Cestari A, Guazzoni G, Barbieri L, Rigaldi P. Current status of local penile therapy. Int J Impo Res 2002;14:S70– 81. Chuang AT, Strauss JD, Murph RA, Steers WD. Phosphodiesterase inhibitor specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro. J Urol 1998;160:257–61. Haas CA, Seftel AD, Razmjouei. K, Ganz MB, Hampel N, Ferguson K. Erectile dysfunction in aging: Upregulation of endothelial nitric oxide synthase. Urology 1998;51:516–22. Azadzoi KM, Goldstein I, Siroky MB, Traish AM, Krane RJ, Saenz de Tejada I. Mechanisms of ischemia induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction. J Urol 1998;160:2216–22. Martinez-Pineiro L, Trigo-Rocha F, Hsu GL, von Heyden B, Lue TF, Tanagho EA. Cyclic guanosine monophosphate mediates penile erection in the rat. Eur Urol 1993;24:492–9. Knispel HH, Goessl C, Beckmann R. Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation. Urology 1992;40:471–6. Martinez-Pineiro L, Trigo-Rocha F, Hsu GL, von Heyden B, Lue TF, Tanagho EA. Cyclic guanosine monophosphate mediates penile erection in the rat. Eur Urol 1993;24:492–9. Brock G, Breza J, Lue TF. Intracavernous sodium nitroprusside: Inappropriate impotence treatment. J Urol 1993;150:864–7. Montorsi F, Salonia A, Zanoni M, Pompa P, Cestari A, Guazzoni G, Barbieri L, Rigatti P. Current status of local penile therapy. Int J Imp Res 2002;14(suppl 1):S70–81. Martinez-Pinerio L, Cortes R, Cuervo E, Lopez-Tello J, Cisneros J, Martinez-Pinerio L. Prospective comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. Eur Urol 1998; 34:350–4. Hellstrom WJ, Monga M, Wang R, Domer FR, Kadowitz PJ, Roberts JA. Penile erection in the primate: Induction with nitric-oxide donors. J Urol 1994;151:1723–7.
117
Intracavernous Sodium Nitroprusside (SNP) versus Papaverine/ Phentolamine in Erectile Dysfunction: A Comparative Study of Short-Term Efficacy and Side-Effects Rany Shamloul, MD,*† Ahmed Atteya, MD,* Abdelrahman Elnashaar, MD,* Amr Gadallah, MD,* Wael Zohdy, MD,* and Wael Abdelsalam, MD* *Department of Andrology Sexology and STDs, Cairo University, Cairo, Egypt; †Department of Physiology, University of Saskatchewan, Saskatoon, Canada ABSTRACT
Objective. The aim of our work is to evaluate the efficacy of intracavernous sodium nitroprusside (SNP) in management of erectile dysfunction (ED) in a clinical comparative study with papaverine/ phentolamine in ED patients. Methods. The study included 40 patients with ED divided into two groups. Group I include 20 patients receiving intracavernous (30 mg papaverine + 1 mg phentolamine) followed 1 week later by intracavernous 300 mg SNP. Group II included 20 patients receiving the same regimen of group I but with intracavernous SNP first followed by papaverine/phentolamine 1 week later. All patients were assessed clinically for their response and any developing complications. Results. The numbers of good and poor responders were not statistically significant (P > 0.05) among the two groups. The mean erectile duration of SNP was similar to bimix (P > 0.05). No side-effects whether local or systemic occurred with SNP while priapism and local penile pain were recorded with bimix solution. Conclusions. Intracavernous pharmacotherapy is still a reliable method both for diagnosis and for treatment of ED. While preliminary results of our study show a potential of SNP to be an effective and safe intracavernous agent, long-term self-injection clinical trials are needed before large-scale usage is recommended. Key Words. Sodium Nitroprusside; Impotence; Intracavernous Drugs
Introduction
E
rectile dysfunction (ED) is defined as the persistent inability to obtain or to maintain penile erection sufficient for satisfactory relations [1]. Intracavernous injection of vasoactive drugs is recognized as an important measure both to diagnose and as a second-line treatment of ED [2]. Many intracavernous vasoactive drugs are used effectively such as papaverine, phentolamine, prostaglandin E1, and their mixtures yet, with considerable side-effects. Short-term undesired effects include priapism and penile pain, while long-term side-effects include cavernous fibrosis [3].
In vivo and in vitro studies suggest that nonadrenergic, noncholinergic relaxation of cavernous smooth muscle is mediated by nitric oxide through activation of the guanosine monophosphate pathway [4]. Sodium nitroprusside (SNP) can result in a dose-dependent increase in cyclic guanosine monophosphate (cGMP) in smooth muscle leading to penile erection [5]. In a recent study Quiang et al. concluded that SNP facilitates relaxation of the penile smooth muscle and penile erection without significant side-effects [6]. The aim of our work is to evaluate the efficacy of intracavernous injection of SNP in management of ED in a clinical comparative study with a bimix J Sex Med 2005; 2: 117–120
118 solution (papaverine + phentolamine) patients.
Shamloul et al. in
ED
Materials and Methods
Two groups were included in this study incorporating 40 patients complaining of ED for more than 1 year and candidates for intracavernous selfinjection program. Twenty-seven patients had previously diagnosed vasculogenic ED, 10 patients had psychogenic ED, and three patients had neurogenic ED. The mean duration of ED was 1.8 ± 0.5 years. The mean age of all patients was 43.5 ± 4.3 years. Detailed history-taking, physical examination including general and local genital examination was performed. All patients had previous unsatisfactory trials of new oral therapies for ED. Group I included 20 patients given an intracavernous 1 mL bimix solution containing 30 mg papaverine + 1 mg phentolamine followed 1 week later by another intracavernous dose of 300 mg SNP. Group II included 20 patients given a single intracavernous dose of 300 mg SNP followed 1 week later by an intracavernous 1 mL bimix solution containing 30 mg papaverine + 1 mg phentolamine. Doses injected of the bimix solution and SNP were previously reported in similar studies [6,7]. Sodium nitroprusside was prepared by dissolving 50 mg of the drug in 2–3 mL of glucose 5%. The concentrated solution was further diluted in 163.5 mL of glucose 5% to provide a solution containing 300 mg SNP per mL. The solution was protected from light and used within 6 hours of preparation. Written informed consents were obtained from all subjects prior to the study. Patients and participating physicians were blinded regarding the nature of the injected drugs.
Technique of Intracavernous Injection All patients underwent an office session of intracavernous injection of the vasoactive substance
injected into the lateral corpus cavernosum through a 30 g needle fixed on a tuberculin syringe. Before injection, a tight rubber band was placed, by a physician, at the base of the penis and left for 2–3 minutes after injection to avoid rapid dispersal of the drug into the systemic circulation. All patients were shown how to apply the rubber band and none of them reported inconvenience. Evaluation of the response was graded according classification of Gerstenberg and associates [8]. Grade 0 was no response postinjection. Grade 1 was minimal tumescence and no rigidity. Grade 2 was moderate tumescence and minimal rigidity. Grade 3 was full tumescence and moderate rigidity. Grade 4 was moderate rigidity but penis could be bent. Grade 5 was full erection. Grades 4 and 5 are sufficient for penetration. Pulse and blood pressure were measured 15 minutes prior and at 15, 30, 60, and 120 minutes following drug administration both in the sitting and standing positions. Any occurring side-effects were recorded and managed accordingly. Priapism (a state of prolonged engorgement or erection of the penis not related to sexual desire or stimulation lasting for 6 hours or more) was treated by repeated aspiration of blood combined with irrigation of saline and intracavernous injection of asypathomimetics (e.g., ephedrine) with careful monitoring of blood pressure. All injections were performed by the same physician, while another physician assessed the grade of erection.
Statistical Analysis Statistical analysis of data was performed using SPSS statistics software for Windows. Pearson chi-square test was used to compare quantitative variables among different classification groups. Results
Table 1 illustrates comparison between intracavernous bimix and SNP regarding erectile duration, side-effects, and efficacy. There was no statistical
Table 1 Comparison between intracavernous bimix and sodium nitroprusside (SNP) as regarding erectile duration, sideeffects, and efficacy
Mean erectile duration (SD) (N = 36) Priapism Penile pain Patients with good response (E4 and E5) Patients with poor response (E2 and E3) * P > 0.05.
J Sex Med 2005; 2: 117–120
Bimix
SNP
48.1 ± 3.8 minutes (4/40) patients 10% (3/40) patients 7.5% (11/40) patients 27.5% (29/40) patients 72.5%
43 ± 2.4 minutes* 0 patients 0 patients (12/40) patients 30%* (28/40) patients 70%
119
Intracavernous SNP in ED Table 2
Blood pressure (BP) changes before and after sodium nitroprusside (SNP) injection
Blood pressure
Before SNP injection
15 minutes after SNP injection
30 minutes after SNP injection
1 hour after SNP injection
2 hours after SNP injection
Systolic BP (mm Hg) Diastolic BP (mm Hg)
117 ± 1.5* 84 ± 1.1
116 ± 2.1 82 ± 1.9
115 ± 1.8 80 ± 2.4
114 ± 3.3 80 ± 2.3
117 ± 1.8 83 ± 2.6
Values are mean ± SD.
significance (P > 0.05) between good and poor responders were not among the two groups. The mean erectile duration regarding bimix was 48.1 ± 3.8 minutes while the mean erectile duration of SNP was 43 ± 2.4 minutes showing no statistical significance (P > 0.05). Table 2 illustrates the blood pressure measurements of all patients before and after intracavernous SNP injection. No significant decrease in blood pressure was noted before and after SNP injection. None of the patients who tried intracavernous SNP experienced prolonged erection while four patients (10%) on bimix solution complained of priapism (three patients with vasculogenic impotence and one with psychogenic impotence). Detumescence was achieved in all patients with priapism following aspiration/irrigation and asypathomimetics injection. Localized penile pain in the form of burning sensation occurred in three cases (7.5%) receiving bimix, while patients receiving SNP did not report this side-effect. No significant changes in blood pressure were recorded after the intracavernous injection of SNP or bimix solution. Discussion
Despite the recent breakthroughs in the development of effective oral treatment of ED, intracavernous pharmacotherapy is still considered by many authors as an effective treatment of ED [9]. Recent reports have demonstrated that in addition to the well-known intracavernous drugs as papaverine, phentolamine, PGE1, and their combinations, newer nitric oxide donor drugs as SNP showed satisfactory response [6]. Nitric oxide generated in response to nonadrenergic and noncholinergic stimulation is the main event leading to vascular smooth muscle relaxation through activation of soluble guanylate cyclase [10]. Nitric oxide also inhibits platelet aggregation and adhesion to endothelial surfaces preventing thrombosis of stagnant blood in sinusoidal spaces during erection [11]. Sodium nitroprusside is commonly used as an antihypertensive agent. It causes an increase in the
intracellular concentration of cGMP) and induces relaxation by activating cGMP-dependent protein kinase, which inactivates the light chain myosin kinase and decreases cytosolic calcium concentration [12]. Several animal studies were conducted to assess the effect of nitric oxide donors on the corpus cavernosum smooth muscles, reporting that nitric oxide activates the synthesis of cGMP and that cGMP causes cavernous smooth muscle relaxation [13–15]. Alprostadil (PGE1) is the most widely used intracavernous drug worldwide. In 1995, Martinez-Pineiro and colleagues reported satisfactory preliminary results of intracavernous SNP in comparison to PGE1 [7]. In Egypt, intracavernous bimix (papaverine + phentolamine), due to its relatively economic price, is used in a large scale to treat ED. This encouraged us to study the efficacy of intracavernous SNP in comparison to the wellestablished bimix solution. In our study there was no significant difference in erectile response among good responders in both groups giving SNP an apparently equal efficacy to bimix solution 30% vs. 27.5%. While these results are similar to that previously reported, our results show a longer erectile duration after intracavernous injection of SNP (43 minutes compared to 24 minutes) [6]. We believe that this may be due to the sufficient time the rubber band was left at the base of the penis, preventing rapid dispersal of SNP to the systemic circulation. Also longer erectile duration renders intracavernous SNP suitable for both diagnosis and treatment of ED. On the other hand the low efficacy of bimix solution in our study may be related to the etiology of ED. Brock and colleagues previously reported severe hypotension with high doses of intracavernous SNP (1,000 mg) which refrained them from continuing their study [16]. Penile pain occurred in the form of burning sensation in 3 (7.5%) out of 40 patients using bimix solution. Previous reports suggested that this may be related to the acidity of the injected solution [17]. Neither local (priapism and penile pain) nor systemic (dizziness, palpitation, and blood pressure changes) sideeffects occurred using SNP. This was also in J Sex Med 2005; 2: 117–120
120 agreement with the results reported previously which advised the use of intracavernous SNP in patients experiencing postinjection penile pain and priapism [18]. We believe that the lack of hypotension in our study may be attributed to the application of the constriction ring during injection and to the use of relatively small dose of SNP. Similar results were previously reported acknowledging that effects of nitric oxide donors on systemic blood pressure were prevented by digital compression at the base of the penis during injection limiting access of the drugs to the systemic circulation [19].
Shamloul et al.
7
8 9
Conclusions
10
Intracavernous pharmacotherapy is still a reliable method for both diagnosis and treatment of ED. While preliminary results of our study show a potential of SNP to be an effective and safe intracavernous agent, long-term self-injection clinical trials are needed before large-scale usage is recommended.
11
Corresponding Author: Rany Shamloul, MD, Department of Andrology Sexology and STDs, Cairo University, Cairo, Egypt. Tel: 1-306-9666619; Fax: 1-306-9666532; E-mail: [email protected]
12
13
References
1 NIH consensus statement on impotence. Int J Impo Res 1993;5:181–7. 2 Ishii N, Watanabe H, Irisawa C, Kikuchi Y, Kubota Y, Kawamura S, Suzuki K, Chiba R, Tokiwa M, Sbirai M. Intracavernous injection of PGE1 for the treatment of erectile impotence. J Urol 1989;141: 323–5. 3 Padma-Nathan H. Minimally invasive therapy for erectile dysfunction: Intracavernosal, oral, transdermal/transglandular and intraurethral approaches. In: Mulchahy JJ, editor. Topics in clinical urology: Diagnosis and management of male sexual dysfunction. NY: Igaku-Shoin; 1997:182–95. 4 Kim N, Azadzoi KM, Goldstein I, de Tejada S. A nitric oxide-like factor mediates nonadrenergic noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991;88: 112–8. 5 Jeremy JY, Ballard SA, Naylor AM, Miller MA, Angelini GD. Effects of sildenafil, a type 5-cGMP phoshpodiesterase inhibitor on cGMP and cAMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 1997;79:958–63. 6 Quiang FU, Yao DH, Jiang YQ. A clinical comparative study on effects of intracavernous injection of J Sex Med 2005; 2: 117–120
14
15
16 17
18
19
sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients. Asian J Androl 2000;2:301–3. Martinez-Pineiro L, Lopez-Tello J, Alonso Dorrego JM, Cisneros J, Cuervo E, Martinez-Pineiro JA. Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. J Urol 1995;153:1487–90. Gerstenberg TC, Nordling J, Hald T, Wagner G. Standardized evaluation of erectile dysfunction in 95 consecutive patients. J Urol 1989;141:857. Montorsi F, Salonia A, Pompa P, Cestari A, Guazzoni G, Barbieri L, Rigaldi P. Current status of local penile therapy. Int J Impo Res 2002;14:S70– 81. Chuang AT, Strauss JD, Murph RA, Steers WD. Phosphodiesterase inhibitor specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro. J Urol 1998;160:257–61. Haas CA, Seftel AD, Razmjouei. K, Ganz MB, Hampel N, Ferguson K. Erectile dysfunction in aging: Upregulation of endothelial nitric oxide synthase. Urology 1998;51:516–22. Azadzoi KM, Goldstein I, Siroky MB, Traish AM, Krane RJ, Saenz de Tejada I. Mechanisms of ischemia induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction. J Urol 1998;160:2216–22. Martinez-Pineiro L, Trigo-Rocha F, Hsu GL, von Heyden B, Lue TF, Tanagho EA. Cyclic guanosine monophosphate mediates penile erection in the rat. Eur Urol 1993;24:492–9. Knispel HH, Goessl C, Beckmann R. Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation. Urology 1992;40:471–6. Martinez-Pineiro L, Trigo-Rocha F, Hsu GL, von Heyden B, Lue TF, Tanagho EA. Cyclic guanosine monophosphate mediates penile erection in the rat. Eur Urol 1993;24:492–9. Brock G, Breza J, Lue TF. Intracavernous sodium nitroprusside: Inappropriate impotence treatment. J Urol 1993;150:864–7. Montorsi F, Salonia A, Zanoni M, Pompa P, Cestari A, Guazzoni G, Barbieri L, Rigatti P. Current status of local penile therapy. Int J Imp Res 2002;14(suppl 1):S70–81. Martinez-Pinerio L, Cortes R, Cuervo E, Lopez-Tello J, Cisneros J, Martinez-Pinerio L. Prospective comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. Eur Urol 1998; 34:350–4. Hellstrom WJ, Monga M, Wang R, Domer FR, Kadowitz PJ, Roberts JA. Penile erection in the primate: Induction with nitric-oxide donors. J Urol 1994;151:1723–7.