Sample records for alprostadil
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Use of medications for erectile dysfunction in the United States, 1996 through 2001.
Wysowski, Diane K; Swann, Joslyn
2003-03-01
We describe the use during 1996 through 2001 of the primary medications approved in the United States for treatment of erectile dysfunction, namely alprostadil injection and urethral suppository, and sildenafil. MATERIALS AND METHODS Two pharmaceutical research data bases, the National Prescription Audit Plus, and National Disease and Therapeutic Index, were accessed and analyzed. Ancillary data were obtained from 2 health plans. Increases in the number of dispensed prescriptions for alprostadil injection and urethral suppository marketed in 1995 and 1996, respectively, were reversed in 1998 by the marketing of sildenafil. From 1998 through 2001 the estimated number of prescriptions for sildenafil increased 1.87-fold or 87% from 7.5 million to 14 million, while those for alprostadil injection decreased 33% from 239,000 to 159,000 and those for alprostadil suppository decreased 67% from 400,000 to 132,000. Sildenafil was prescribed proportionately more frequently for younger men than alprostadil injection or suppository (p <0.0001). Compared with men for whom sildenafil was prescribed in 1998 those prescribed the drug in 2001 were younger (p <0.0001). Alprostadil injection and suppository were prescribed proportionately more frequently by urologists than sildenafil. Ancillary data from 2 health plans indicated a 173% increase in 1 plan and a 25% decrease in the other due to restrictions in sildenafil prescriptions from 1998 through 2001. Due to the marketing of sildenafil in 1998 through 2001 the use of 2 approved medications for erectile dysfunction, namely alprostadil injection and alprostadil urethral suppository, decreased, while the use of sildenafil increased. Sildenafil was prescribed proportionately more frequently for younger men than alprostadil injection or suppository. Alprostadil was prescribed proportionately more frequently by urologists than sildenafil, which was most commonly prescribed by family and general practitioners, and internists. The data indicate the wide adoption and use of sildenafil for erectile dysfunction.
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Treatment of ischemic ulcers of the lower limbs with alprostadil (prostaglandin E1).
Tondi, Paolo; Gerardino, Laura; Santoliquido, Angelo; Pola, Roberto; Gabrielli, Maurizio; Papaleo, Pierangelo; Gasbarrini, Antonio; Pola, Paolo; Flore, Roberto
2004-08-01
Hemodynamic, hemorheologic, and metabolic changes are main determinants in the genesis of ischemic leg ulcers. Because prostaglandin E1 (alprostadil) could successfully counteract these changes, it has been intravenously used in the treatment of this disease. The aim of this study was to evaluate the efficacy of alprostadil in the treatment of ischemic ulcers and to compare subcutaneous with intravenous administration. Eighty patients were enrolled. Twenty-five were treated by injecting low doses of alprostadil around ischemic ulcers of the leg and saline solution intravenously and 25 were treated with intravenous alprostadil and local injections of saline solution; the control group was composed of 30 patients who received saline solution around the ulcers and intravenously. All patients showed a statistically significant improvement in ulcer diameter, pain, and transcutaneous oxygen pressure compared to the control group. No relevant differences in the clinical outcome in the two treated groups were found, but patients treated with subcutaneous alprostadil experienced no side effects and showed higher values of transcutaneous oxygen pressure. Both intravenous and local subcutaneous alprostadil are useful in the treatment of ischemic leg ulcers, but subcutaneous administration is less expensive and easier to perform.
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... cartridges at room temperature and away from excess heat and moisture (not in the bathroom). Read the manufacturer's instructions for information about how long alprostadil solution may be stored after mixing and where it ...
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Stability of Alprostadil in 0.9% Sodium Chloride Stored in Polyvinyl Chloride Containers.
McCluskey, Susan V; Kirkham, Kylian; Munson, Jessica M
2017-01-01
The stability of alprostadil diluted in 0.9% sodium chloride stored in polyvinyl chloride (VIAFLEX) containers at refrigerated temperature, protected from light, is reported. Five solutions of alprostadil 11 mcg/mL were prepared in 250 mL 0.9% sodium chloride polyvinyl chloride (PL146) containers. The final concentration of alcohol was 2%. Samples were stored under refrigeration (2°C to 8°C) with protection from light. Two containers were submitted for potency testing and analyzed in duplicate with the stability-indicating high-performance liquid chromatography assay at specific time points over 14 days. Three containers were submitted for pH and visual testing at specific time points over 14 days. Stability was defined as retention of 90% to 110% of initial alprostadil concentration, with maintenance of the original clear, colorless, and visually particulate-free solution. Study results reported retention of 90% to 110% initial alprostadil concentration at all time points through day 10. One sample exceeded 110% potency at day 14. pH values did not change appreciably over the 14 days. There were no color changes or particle formation detected in the solutions over the study period. This study concluded that during refrigerated, light-protected storage in polyvinyl chloride (VIAFLEX) containers, a commercial alcohol-containing alprostadil formulation diluted to 11 mcg/mL with 0.9% sodium chloride 250 mL was stable for 10 days. Copyright© by International Journal of Pharmaceutical Compounding, Inc.
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Goldstein, Sue W; Gonzalez, Joshua R; Gagnon, Catherine; Goldstein, Irwin
2016-09-01
Female sexual arousal disorder is a pathophysiologic state characterized clinically by persistent or recurrent inability to attain or maintain an adequate lubrication-swelling response of sexual excitement until completion of sexual activity. Prior clinical experience with alprostadil products for men with erectile dysfunction supports its use in women with female sexual arousal disorder. To compare the effect of topical alprostadil with over-the-counter (OTC) lubricant on female genital arousal in the absence of visual sexual stimuli. Healthy premenopausal women without sexual dysfunction were recruited from the community to participate in the study. Of 17 women who consented, 10 were enrolled and completed the trial. The mean age of subjects was 32 years (range = 27-43). Study drug or placebo was applied topically to the genitals. Continuous temperature monitoring was performed. Participants completed questionnaires assessing genital sensation, effect, intensity, and duration. Change in temperature from baseline in vestibule, clitoris and vulva. In all 10 subjects, topical alprostadil induced a statistically significant increase in temperature of the vestibule, clitoris, and vulva compared with the OTC lubricant. The most rapid difference in genital temperature between placebo and alprostadil was seen on the vulva, which demonstrated a significant difference at approximately 9 minutes. There was a significant difference in temperature seen for the vestibule and clitoris at 11 and 19 minutes, respectively. Sixty percent of women reported being aware or conscious of genital sensations with topical alprostadil, but not with OTC lubricant. Discordance was noted in 30% of subjects who reported being aware or conscious of genital sensations with the two treatments and 10% who reported not being aware or conscious of genital sensations with either treatment. Topical alprostadil administered to healthy premenopausal women induced statistically significant, sustained increases in genital temperatures of the vestibule, clitoris, and vulva within 20 minutes compared with OTC lubricant. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Use of intraurethral alprostadil in patients not responding to sildenafil citrate.
Jaffe, Jamison S; Antell, Mara R; Greenstein, Marc; Ginsberg, Phillip C; Mydlo, Jack H; Harkaway, Richard C
2004-05-01
To determine whether intraurethral alprostadil would be an effective alternative for men with erectile dysfunction who did not respond adequately to sildenafil citrate but desired minimally invasive treatment. A total of 44 male patients aged 41 to 74 years with erectile dysfunction refractory to treatment with sildenafil citrate were enrolled in this study. Of the 44 patients, 10 had undergone prior radical retropubic prostatectomy. The patients were evaluated for subjective improvement in an office setting and completed the Sexual Health Inventory for Men questionnaire as an objective assessment of improved erectile ability. Success was defined as subjective improvement in erectile function, as well as an improved Sexual Health Inventory for Men score. Of the 44 men, 13 (29.5%) responded successfully to intraurethral alprostadil, with a follow-up ranging from 2 to 15 months. The remaining 31 men had no response (n = 28, 90%), refused escalating doses (n = 2, 7%), or were lost to follow-up (n = 1, 3%). In the subgroup of 10 men with prior radical retropubic prostatectomy, 5 (50%) reported success with intraurethral alprostadil (500 microg in 2 patients and 1000 microg in 3 patients). Although sildenafil citrate remains the most common initial therapy in men with erectile dysfunction, intraurethral alprostadil may be a reasonable treatment option for sildenafil nonresponders. This may be especially true in men having undergone prior radical retropubic prostatectomy.
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Mydlo, J H; Volpe, M A; Macchia, R J
2000-07-01
Intraurethral alprostadil and oral sildenafil are useful in selected patients. However, there continues to be a significant treatment failure rate. Since their mechanisms of action are different, we wanted to evaluate the effectiveness of combination therapy. Of 214 patients treated for erectile dysfunction (ED), 65 were not fully satisfied with the firmness of their erections via monotherapy. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Group I consisted of 33 patients who tried maximal dose intraurethral alprostadil monotherapy initially, followed by the maximal dose of sildenafil monotherapy, and were still unsatisfied. Group II consisted of 32 patients who tried the maximal dose sildenafil monotherapy initially, followed by the maximal dose of alprostadil monotherapy, and were also unsatisfied. There 65 patients then underwent combination therapy. 60 out of the 65 patients stated they were satisfied with combination therapy. Questionnaire scores for erectile function were 23.1+/-2.0 (114%) for combination therapy vs. 19.2+/-1.8 (77%) and 15.2+/-1.6 (41%) for sildenafil and alprostadil monotherapies (p<0.05). There were no significant differences in responses between the two groups. The men also reported improvement in intercourse and overall satisfaction. Combination therapy may be an option for motivated patients who have a suboptimal response from monotherapy.
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Sheehy, Philip M; Ramstad, Tore
2005-10-04
The binding constant between alprostadil (PGE1) and alpha-cyclodextrin (alpha-CD) was determined at four temperatures using conductance measurements. Alpha-cyclodextrin is an excipient material in Caverject dual chamber syringe (DCS) that was added to enhance stability. The binding constant was used to calculate the amount of PGE1 free upon reconstitution and injection, since only the free drug is clinically active. The conductivity measurement is based on a decrease in specific conductance as alprostadil is titrated with alpha-CD. The change in conductivity was plotted versus free ligand concentration (alpha-CD) to generate a binding curve. As the value of the binding constant proved to be dependent on substrate concentration, it is really a pseudo binding constant. A value of 742+/-60 M(-1) was obtained for a 0.5 mM solution of alprostadil at 27 degrees C and a value of 550+/-52 M(-1) at 37 degrees C. These results compare favorably to values previously obtained by NMR and capillary electrophoresis. Calculation of the fraction PGE1 free upon reconstitution and injection show it to approach the desired outcome of one. Hence, the amount of drug delivered by Caverject DCS is nominally equivalent to that delivered by Caverject S. Po., a predecessor product that contains no alpha-cyclodextrin.
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Zhang, L; Zhang, H-Y; Huang, F-C; Huang, Q; Liu, C; Li, J-R
2016-09-01
We investigated the clinical value of alprostadil combined with the α-lipoic acid in treating type 2 diabetes mellitus with erectile dysfunction (DMED). We selected a total of 76 cases of patients who were admitted to endocrinology department of our hospital from June 2014 to June 2015 and diagnosed as DMED, and the average age was (46.7 ± 7.2) years old, average course of diabetes mellitus was (6.2 ± 2.8) years and average body mass index was (25.4 ± 1.3) kg/m2. 40 cases were randomly divided in the observation group while 36 cases were divided in the control group. They received blood glucose control therapy. The patients in the observation group received 60 mg alprostadil hydrochloride and 600 mg α-lipoic acid added into 250 mL normal saline, intravenous drip once per day for 2 weeks. The patients in the control group took tadalafil 5 mg orally, once per night for 2 weeks as a course of treatment. There were no cases of loss. The effective rate of treatment in observation group is significantly higher than that in the control group (95.0% vs. 80.5%, p < 0.05). The score of IIEF-5, EHGS and the FMD value of brachial artery of the observation group after the operation were significantly higher than that of the control group (p < 0.05). The adverse reaction rate in the observation group was lower than that in the control group (7.5% vs. 13.9%, p < 0.05). Alprostadil combined with α-lipoic acid can improve DMED patients' vascular endothelial function and erection hardness to treat erectile dysfunction with less adverse effects and better safety.
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Mydlo, J H; Volpe, M A; MacChia, R J
2000-09-01
To evaluate the outcome of combined therapy (using intraurethral alprostadil and oral sildenafil) in private and clinic patients with erectile dysfunction, and thus assess predictors of satisfaction. In all, 360 men were treated for erectile dysfunction using single and/or combined therapy, comprising 214 private-practice and 166 clinic patients. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Serum testosterone levels, education and socio-economic status were also assessed. Group 1a consisted of 33 private patients and Group 1b of 24 clinic patients who tried the maximum dose of intraurethral alprostadil monotherapy initially, followed by the maximum dose of sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32 private patients and group 2b of 31 clinic patients who tried the maximum dose of sildenafil monotherapy initially, followed by the maximum dose of alprostadil monotherapy, and were also dissatisfied. These two groups of 65 private and 55 clinic patients then underwent combined therapy. The mean (SD) score for erectile function was 24.1 (2) for combined therapy (a 123% improvement), and 19.8 (1. 8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and alprostadil monotherapies (P < 0.05 for both patient groups). The men also reported an improvement in their satisfaction with intercourse. However, at 18 months, 60 of the 65 private patients but only 40 of the 55 clinic patients continued with combined therapy; thus, the discontinuation rate was three times greater among clinic than among private patients. Furthermore, the private patients had an overall improvement in the satisfaction score of 128%, compared with 51% for the clinic patients. Although there were no significant differences in erectile function improvement within the two satisfied combined therapy groups, the differences in overall satisfaction and long-term withdrawal rates suggests that other factors beside motivation must be involved for success, e.g. education, persistence, realistic expectations, and certain psychological factors. Combined therapy should be considered for those patients who have a suboptimal response to monotherapy and refuse or are not candidates for surgical options. Generally, those patients with a higher education, greater persistence and more realistic expectations were more satisfied with combined therapy.
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Feng, Z; Hu, Y; An, N N; Feng, W J; Hu, T; Mao, Y J
2018-02-12
Objective: To observe the effects of acidic oligosaccharides (AOS) on P-selectin levels in the serum and the pulmonary arteries of pulmonary hypertensive rats induced by monocrotaline. Methods: Sixty healthy adult male Sprague-Dawley rats were randomly divided into control group ( n =10), model group ( n =10), Alprostadil group ( n =10), low-dose AOS group (AOS-L, n =10), medium-dose AOS group (AOS-M, n =10) and high-dose AOS group (AOS-H, n =10). The rat model of pulmonary arterial hypertension was made by a single intraperitoneal injection of monocrotaline(60 mg/kg). Five weeks after injection, pulmonary arterial (PA) acceleration time (PAT) and ejection time (ET) were measured by color Doppler ultrasound. Then, the Alprostadil group was treated by Alprostadil 5 μg·kg(-1)·d(-1)intraperitoneally. Acidic oligosaccharides was administered by intraperitoneal injection to rats in the AOS-L group(5 kg(-1)·d(-1)), AOS-M group (10 mg·kg(-1)·d(-1))and AOS-H group (20 mg·kg(-1)·d(-1)). Control group and model group were given normal saline instead. At the end of experiments, the death rate was recorded and PAT/ET was measured. We calculated the right ventricular hypertrophy index (RVHI) of all rats sacrificed under anesthesia. Precision-cut lung slices were stained with HE for observation of the structure of middle and small arteries. The expression level of P-selectin in serum and pulmonary arterial tissues were detected by ELISA and Western blot respectively. Results: AOS significantly increased the level of PAT/ET ( P <0.01), and attenuated RVHI ( P <0.01). AOS significantly improved intima-media proliferation in small-to medium-sized pulmonary arteries, and attenuated perivascular inflammation. AOS and Alprostadil significantly down-regulated the protein expression of P-selectin in serum and pulmonary arteries ( P <0.01). Conclusion: In this rat model of monocrotaline-induced pulmonary hypertension, AOS decreased the expressions of P-selectin in serum and pulmonary arteries in a dose-dependent manner.
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Rastrelli, Giulia; Corona, Giovanni; Monami, Matteo; Melani, Cecilia; Balzi, Daniela; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario
2011-12-01
Intracavernous alprostadil injection (ICI) test has been considered useless in assessing the vascular status of subjects with erectile dysfunction (ED). To analyze the clinical correlates of ICI test in patients with ED and to verify the value of this test in predicting major adverse cardiovascular events (MACE). A consecutive series of 2,396 men (mean age 55.9 ± 11.9 years) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of this sample (N = 1,687) was enrolled in a longitudinal study. Several clinical, biochemical, and instrumental (penile color Doppler ultrasound; PCDU) factors were evaluated. All patients underwent an ICI test, and responses were recorded on a four-point scale ranging from 1 = no response to 4 = full erection. Among the patients studied, 16.4%, 41.2%, 40.2% and 2.2% showed grade 4, 3, 2, and 1 ICI test response, respectively. After adjusting for confounders, subjects with grade 1 ICI test response showed reduced perceived sleep-related, masturbation-related, and sexual-related erections when compared with the rest of the sample. In addition, a worse response to ICI test was associated with a higher prevalence of hypogonadism-related symptoms and signs along with lower testosterone levels. The prevalence of both diabetes mellitus and metabolic syndrome was inversely related to ICI test response. Accordingly, dynamic and basal peak systolic velocity (PSV), as well as acceleration at PCDU, decreased as a function of ICI test response. In the longitudinal study, after adjusting for confounders, grade 1 response was independently associated with a higher incidence of MACE (hazard ratio = 2.745 [1.200-6.277]; P < 0.05). These data were confirmed even when only subjects with normal PSV (>25 cm/s) were considered. Our results demonstrate that poor ICI test response is associated with several metabolic disturbances and higher incidence of MACE. We strongly recommend performing ICI test with alprostadil in all ED subjects. © 2011 International Society for Sexual Medicine.
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Zhang, Miao; Liao, Qin-ping; Yao, Chen; Geng, Li; Wang, Xiang-ping; Song, Xue-hong; Zhao, Jian; Lv, Tao; Lv, Ming-qi; Chen, Lei; Yao, Yan-jun; Xia, Bei; Zhang, Hai-zhen; Wang, Qiu-xi; Lu, Jun-li
2010-12-18
To investigate the efficacy and safety of alprostadil cream in management of female sexual arouse disorder (FSAD), and its appropriate dose for clinical prescription. The volunteers were assigned randomly to four groups which received alprostadil cream in different dosage (500 μg, 700 μg and 900 μg) or placebo cream, respectively. The cream was applied to the clitoris and G-spot before coitus. The efficacy was assessed by comparing the satisfactory rate of sexual arousal, the score of female sexual function index (FSFI) and female sex disorder scale (FSDS) and the general appraised question (GAQ) before and after the treatment. The safety was evaluated by the adverse effects that appeared including symptoms, physical and biochemical examination. Totally, 400 women enrolled in this study with 374 assigned to the group for efficacy evaluation and 387 cases to the group for safety analysis. No significant difference was found among the four groups in the demographic characters and sexual baseline. The increase of satisfactory percentage of sexual arousal in the four groups (placebo, 500 μg, 700 μg and 900 μg) was 22.63%, 36.67%, 34.01%, and 44.29%, respectively (P<0.05), and the increase was statistically higher in the 900 μg group than in the placebo group (P<0.0167). The elevated FSFI score above the baseline in the treatment groups (900 μg 22.89, 700 μg 21.69, and 500 μg 20.71) were higher than that in the placebo group (14.68, P<0.05), while the reduced FSDS score below the baseline (900 μg 25.97, 700 μg 21.98, and 500 μg 20.27) were higher than that of the placebo (17.60, P<0.05). No significant difference was found in the four groups in GAQ (P=0.054). The main common adverse effect was topical stimulation. No adverse effect was reported in physical and biochemical examination, electrocardiogram (ECG) or Thinprep cytologic test (TCT). Alprostadil cream can treat female sexual arousal disorder effectively with the maximum effect at the dose of 900 μg and without significant adverse effect except for mild topical stimulation.
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Mydlo, Jack H; Viterbo, Rosalia; Crispen, Paul
2005-04-01
To report experience with combined therapy using intracorporal injection (ICI) of alprostadil and oral phosphodiesterase 5 (PDE-5) inhibitors for the minimally invasive treatment of erectile dysfunction (ED) after radical prostatectomy (RP), as PDE-5 inhibitors are effective but a few patients may have a suboptimal response. In a retrospective study, 34 men (aged 46-66 years) had a nerve-sparing retropubic RP and subsequent ED. Patients were titrated on sildenafil citrate or vardenafil to maximum doses. All had a suboptimal response after a maximum of eight doses of oral therapy and were then treated with ICI therapy using 15 or 20 microg alprostadil. Erectile function was assessed with the Sexual Health Inventory for Men (SHIM). Of the 32 patients who continued combined therapy, 22 (68%) had an improvement in erectile function after ICI therapy, as assessed by the SHIM score. On follow-up, 36% of these patients used ICI therapy only intermittently, instead of regularly, as they felt that this was adequate enough for good results. PDE-5 oral pharmacotherapy is the most commonly used effective therapy for ED but may not be as effective in patients who have radical surgery; the addition of testosterone patches may have side-effects or be considered a risk in patients with a history of prostate cancer. The use of ICI therapy as an adjunct or maintenance therapy to their oral medication may be another alternative in these patients.
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Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K
2016-07-01
This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. Copyright © 2016 Elsevier Inc. All rights reserved.
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Lee, Mary; Sharifi, Roohollah
2018-03-01
Phosphodiesterase type 5 inhibitors (PDE5Is) are the drug of choice for medical management of erectile dysfunction (ED). On-demand PDE5Is have an overall efficacy of 60-70% for ED; 30-35% of patients fail to respond to a PDE5I, and 30-50% of non-responders can be salvaged with detailed counseling on proper use and physician follow-up to ensure that the patient has been prescribed an appropriate and full PDE5I clinical trial. True non-responders may be offered intracavernosal injections of erectogenic drugs, intraurethral alprostadil, or surgical insertion of a penile prosthesis. Such options are not discreet and are associated with more adverse effects than PDE5Is. Thus patients may request additional non-invasive medical management options. This review describes published literature on patients who failed to respond to an on-demand PDE5I regimen and were treated with a non-invasive PDEI-based regimen, including switching from one PDE5I to another; increasing the dose of PDE5I above the labeled dosage range; using two PDE5Is concurrently; using a daily PDE5I regimen; or combining a PDE5I with a testosterone supplement, α-adrenergic antagonist, intraurethral or intracavernosal alprostadil, vacuum erection device, or low-intensity shock wave therapy. The limitations of published clinical trials do not allow for sufficient evidence to recommend one option over another. Therefore, in PDE5I-refractory patients, the choice of a specific next step should be individualized based on the preference of the patient and his sexual partner, the advantages and disadvantages of the various options, the concurrent medical illnesses and medications of the patient, and the patient's response to treatment.
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Advances in the treatment of erectile dysfunction: what’s new and upcoming?
Patel, Chintan K.; Bennett, Nelson
2016-01-01
Erectile dysfunction adversely affects up to 20% of all men and is the most commonly treated sexual disorder. The public health implications of this condition are significant and represent a challenge for our healthcare system. The physiological pathways responsible for erections have been extensively studied, and much advancement has been made since the introduction of phosphodiesterase 5 inhibitors. Newer agents, such as dopaminergic and melanocortin receptor agonists, which target central erectogenic pathways, are under investigation. Newer formulations and delivery methods of existing medications such as alprostadil will also be introduced in the near future. Furthermore, low-intensity shockwave lithotripsy and stem cell regenerative techniques are innovative approaches to the treatment of erectile dysfunction. PMID:27516878
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Cutaneous Polyarteritis Nodosa Presented with Digital Gangrene: A Case Report
Lew, Sogu; Cho, Sung Do; Cha, Hee Jeong; Eum, Eun-A; Jung, Hyun Chul; Park, Jae Hoo
2006-01-01
Cutaneous polyarteritis nodosa (CPAN) is an uncommon form of vasculitis involving small and medium sized arteries of unknown etiology. The disease can be differentiated from polyarteritis nodosa by its limitation to the skin and lack of progression to visceral involvement. The characteristic manifestations are subcutaneous nodule, livedo reticularis, and ulceration, mostly localized on the lower extremity. Arthralgia, myalgia, peripheral neuropathy, and constitutional symptoms such as fever and malaise may also be present. We describe a 34-yr-old woman presented with severe ischemic change of the fingertip and subcutaneous nodules without systemic manifestations as an unusual initial manifestation of CPAN. Therapy with corticosteroid and alprostadil induce a moderate improvement of skin lesions. However, necrosis of the finger got worse and the finger was amputated. PMID:16614534
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Kirkham, A
2012-01-01
MRI of the penis is an expensive test that is not always superior to clinical examination or ultrasound. However, it shows many of the important structures, and in particular the combination of tumescence from intracavernosal alprostadil, and high-resolution T2 sequences show the glans, corpora and the tunica albuginea well. In this paper we summarise the radiological anatomy and discuss the indications for MRI. For penile cancer, it may be useful in cases where the local stage is not apparent clinically. In priapism, it is an emerging technique for assessing corporal viability, and in fracture it can in most cases make the diagnosis and locate the injury. In some cases of penile fibrosis and Peyronie's disease, it may aid surgical planning, and in complex pelvic fracture may replace or augment conventional urethrography. It is an excellent investigation for the malfunctioning penile prosthesis. PMID:23118102
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Kirkham, A
2012-11-01
MRI of the penis is an expensive test that is not always superior to clinical examination or ultrasound. However, it shows many of the important structures, and in particular the combination of tumescence from intracavernosal alprostadil, and high-resolution T(2) sequences show the glans, corpora and the tunica albuginea well. In this paper we summarise the radiological anatomy and discuss the indications for MRI. For penile cancer, it may be useful in cases where the local stage is not apparent clinically. In priapism, it is an emerging technique for assessing corporal viability, and in fracture it can in most cases make the diagnosis and locate the injury. In some cases of penile fibrosis and Peyronie's disease, it may aid surgical planning, and in complex pelvic fracture may replace or augment conventional urethrography. It is an excellent investigation for the malfunctioning penile prosthesis.
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Kohno, Emiko; Nishikata, Mayumi; Okamura, Noboru; Matsuyama, Kenji
2008-01-01
Prostaglandin E(1) (PGE(1); Alprostadil Alfadex) is a potent vasodilator and inhibitor of platelet aggregation used to treat patients with peripheral vascular disease. The main adverse effects of intravenous PGE(1) administration, phlebitis and venous pain, arise from the unphysiologically low pH of infusion solutions. When PGE(1) infusion solutions with a pH value greater then 6 are used, phlebitis and venous pain are considered to be avoidable. Beginning with a PGE(1) infusion solution with pH greater than 6, we add the amount of 7% sodium bicarbonate needed to bring the solution to pH 7.4 if phlebitis or venous pain develops. In the present study we established a convenient nomogram showing the relationship between the titratable acidity of various infusion solutions and the volume of 7% sodium bicarbonate required to attain pH 7.4 for preventing the phlebitis and venous pain associated with PGE(1) infusion.
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Erectile dysfunction post-radical prostatectomy – a challenge for both patient and physician
Bratu, O; Oprea, I; Marcu, D; Spinu, D; Niculae, A; Geavlete, B; Mischianu, D
2017-01-01
Post-radical prostatectomy erectile dysfunction (post RP ED) is a major postoperative complication with a great impact on the quality of life of the patients. Until present, no proper algorithm or guideline based on the clinical trials has been established for the management of post RP ED. According to literature, it is better to initiate a penile rehabilitation program as soon as possible after surgery than doing nothing, in order to prevent and limit the postoperative local hypoxygenation and fibrosis. The results of numerous clinical trials regarding the effectiveness of the phosphodiesterase 5 inhibitors therapy on post RP ED have made them the gold standard treatment. Encouraging results have been achieved in studies with vacuum erectile devices, intraurethral suppositories with alprostadil and intracavernosal injections, but due to their side effects, especially in the cases of intracavernosal injections and intraurethral suppositories, their clinical use was limited therefore making them a second line option for the post RP ED treatment. What should not be forgotten is that penile implant prosthesis has proven very effective, numerous studies confirming high rates of satisfaction for both patients and partners. PMID:28255370
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Trifiletti, A; Bartolone, S; Scamardi, R; Pizzoleo, M A; Attinà, A; Sottilotta, G; Canobbio, V; Soraci, S; Barbera, N
1999-03-01
In this study the action of a prostaglandin, PGE1, was studied in a group of patients with peripheral arterial occlusive disease (PAOD). In 16 patients (14 men and 2 women, aged 47-70 years, mean 57 +/- 7) with PAOD, Fontaine stage IIb and III in critical ischemia, the effects on two indexes of thrombin generation and action of the endovenous administration (2 hours) of 60 micrograms of Alprostadil-PGE1 for four weeks were evaluated. In all artheriopathic patients, before and after pharmacological treatment, the following haemostatic parameters were evaluated: the prothrombin fragment 1 + 2 (F1 + 2) and the fibrinopeptide A(FPA). The patients showed plasma levels of FPA significantly decreased at the end of the treatment. On the other hand, no significant difference in plasma F1 + 2 levels was observed after treatment. These results seem to indicate that plasma F1 + 2 levels are significantly elevated, as a marker of thrombosis status, in patients with PAOD before and after treatment with PGE1.
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A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.
Mirone, V; Sorrentino, R; di Villa Bianca, R; Imbimbo, C; Palmieri, A; Fusco, F; Tajana, G; Cirino, G
2000-01-01
The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.
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Management of erectile dysfunction post-radical prostatectomy
Saleh, Alan; Abboudi, Hamid; Ghazal-Aswad, MB; Mayer, Erik K; Vale, Justin A
2015-01-01
Radical prostatectomy is a commonly performed procedure for the treatment of localized prostate cancer. One of the long-term complications is erectile dysfunction. There is little consensus on the optimal management; however, it is agreed that treatment must be prompt to prevent fibrosis and increase oxygenation of penile tissue. It is vital that patient expectations are discussed, a realistic time frame of treatment provided, and treatment started as close to the prostatectomy as possible. Current treatment regimens rely on phosphodiesterase 5 inhibitors as a first-line therapy, with vacuum erection devices and intraurethral suppositories of alprostadil as possible treatment combination options. With nonresponders to these therapies, intracavernosal injections are resorted to. As a final measure, patients undergo the highly invasive penile prosthesis implantation. There is no uniform, objective treatment program for erectile dysfunction post-radical prostatectomy. Management plans are based on poorly conducted and often underpowered studies in combination with physician and patient preferences. They involve the aforementioned drugs and treatment methods in different sequences and doses. Prospective treatments include dietary supplements and gene therapy, which have shown promise with there proposed mechanisms of improving erectile function but are yet to be applied successfully in human patients. PMID:25750901
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Galiano, Marc; Rouprêt, Morgan; Beley, Sébastien; Gattegno, Bernard; Chartier-Kastler, Emmanuel; Richard, François
2007-04-01
To assess the value of visual sexual stimulation combined with intracavernous injections (ICI) in patients treated for severe erectile dysfunction. All patients with severe erectile dysfunction were prospectively included in this study between 2005 and 2006. The outpatient protocol consisted of comparing the efficacy of alprostadil ICI alone on D0 and ICI combined with erotic stimulation on D8. End-points were: time to onset and rigidity of erection. A subjective score (1 to 5) was used to quantify erection. Forty patients with a mean age of 64.5 years (range: 52-70 years) were included in the study. All patients had an IIEF5 score less than 15. Erectile dysfunction was secondary to urological surgery in 35% of cases. The mean time to onset of erection was 10 min 18 s (range: 2-20 min) on D0 and 10 min 50 s (range: 2-20 min) on D8. No significant difference for rigidity and quality of erection was observed between D0 and D8 and erections were scored as 5 in 30 cases (75%), 4 in 8 cases (20%) and 3 in 2 cases (5%) at each visit. Visual sexual stimulation has not been demonstrated to be truly effective in the hospital setting in combination with intracavernous injections. In order to increase the patient satisfaction rate, the urologist must above all educate the patient in the intracavernous injection technique in an appropriate environment.
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Yin, Lei; Meng, Xiangjun; Zhou, Xiaotong; Zhang, Tinglan; Sun, Heping; Yang, Zhichao; Yang, Bo; Xiao, Ning; Fawcett, J Paul; Yang, Yan; Gu, Jingkai
2015-08-15
A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500μL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150×2.0mm, 5μm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5→329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2→323.2, and 357.1→321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of ≤6.75% and accuracy (as relative error) of ≤7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate. Copyright © 2015 Elsevier B.V. All rights reserved.
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Usta, M F; Sanabria, J; Bivalacqua, T J; Hellstrom, W J G; Sanabriav, J
2004-02-01
The objective of this study was to evaluate the efficacy of topically applied prostaglandin E1 (PGE(1))+5% SEPA (soft enhancement of percutaneous absorption) on the glans penis in a feline erection model. Erectile response after glans penis administration of PGE(1)+5% SEPA cream (Topiglan, MacroChem Co., Lexington, MA, USA) was compared to the erectile response after intracavernosal administration of the triple-drug combination (1.65 mg papaverine, 25 microg phentolamine, and 0.5 microg PGE(1)). The placebo cream and increasing concentrations (0.25%, 2.5 mg/ml; 0.5%, 5 mg/ml; and 1%, 10 mg/ml) of PGE(1)+5% SEPA were applied in a total volume of 0.1 ml via a plastic needle-less syringe. The control triple-drug combination was administrated intracavernosally via a 30-gauge needle at the completion of each experiment to serve as a control reference. With each application of placebo, PGE(1)+SEPA, and the triple-drug combination, changes in intracavernosal pressure and systemic blood pressure were continuously monitored. Topical application of PGE(1)+SEPA induced increases in intracavernosal pressure in a dose-dependent manner, with minimal effects on systemic blood pressure. The increases obtained with 1% PGE(1) Topiglan cream were similar to the intracavernosal pressure values elicited by the standard intracavernosal triple-drug combination. These data demonstrate that topical glans penis application of PGE(1)+SEPA can induce an erectile response in cats with minimal systemic adverse effects. Oral pharmacological agents are the first-line treatment for male ED. Studies investigating the effectiveness of noninvasive modalities such as topical therapy should continue, because these agents have the potential to avoid the systemic effects commonly seen with oral therapies. Additionally, topical therapy may also benefit patients who are unresponsive to oral agents or have explicit contraindications. Topical PGE(1) application to the glans penis may become an important treatment option in selected patients suffering from erectile dysfunction.
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Herwig, Ralf; Sansalone, Salvatore
2015-03-31
We evaluated the effectiveness of pelvic vein embolization with aethoxysclerol in aero-block technique for the treatment of impotence due to venous leakage in men using sildenafil for intercourse. The aim of the procedure was to reduce the use of sildenafil. A total of 96 patients with veno-occlusive dysfunction, severe enough for the need of PDE5 inhibitors for vaginal penetration, underwent pelvic venoablation with aethoxysclerol. The mean patient age was 53.5 years. Venous leaks were identified by Color Doppler Ultrasound after intracavernous alprostadil injection. Under local anesthesia a 20-gauge needle was inserted into the deep dorsal penile vein. The pelvic venogram was obtained through deep dorsal venography. Aethoxysclerol 3% as sclerosing agent was injected after air-block under Valsalva manoeuver. Success was defined as the ability to achieve vaginal insertion without the aid of any drugs, vasoactive injections, penile prosthesis, or vacuum device. Additionally, a pre- and post- therapy IIEF score and a digital overnight spontaneous erections protocol (OSEP) with the NEVA™-system was performed. At 3 month follow-up 77 out of 96 patients (80.21%) reported to have erections sufficient for vaginal insertion without the use of any drug or additional device. Four (4.17%) patients did not report any improvement. Follow up with color Doppler ultrasound revealed a new or persistent venous leakage in 8 (8.33%) of the patients. No serious complications occurred. Our new pelvic venoablation technique using aethoxysclerol in air-block technique was effective, minimally invasive, and cost-effective. All patients were able to perform sexual intercourse without the previously used dosage of PDE5 inhibitor. This new method may help in patients with contra-indications against PDE5 inhibitors, in patients who cannot afford the frequent usage of expensive oral medication or those who do not fully respond to PDE5-inhibitors.
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Hatzimouratidis, Konstantinos; Hatzichristou, Dimitrios G
2005-01-01
The field of erectile dysfunction (ED) has been revolutionised over the last two decades. Several treatment options are available today, most of which are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken in order to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice of most physicians and patients for the treatment of ED. PDE5 inhibitors have differences in their pharmacological profiles, the most obvious being the long duration of action of tadalafil, but there are no data supporting superiority for any one of them in terms of efficacy or safety. Sublingual apomorphine has limited efficacy compared with the PDE5 inhibitors, and its use is limited to patients with mild ED. Treatment failures with oral drugs may be due to medication, clinician and patient issues. The physician needs to address all of these issues in order to identify true treatment failures. Patients who are truly unresponsive to oral drugs may be offered other treatment options.Intracavernous injections of alprostadil alone, or in combination with other vasoactive agents (papaverine and phentolamine), remain an excellent treatment option, with proven efficacy and safety over time. Topical pharmacotherapy is appealing in nature, but currently available formulations have limited efficacy. Vacuum constriction devices may be offered mainly to elderly patients with occasional intercourse attempts, as younger patients show limited preference because of the unnatural erection that is associated with this treatment modality. Penile prostheses are generally the last treatment option offered, because of invasiveness, cost and non-reversibility; however, they are associated with high satisfaction rates in properly selected patients. All treatment options are associated with particular strengths and weaknesses. A patient-centred approach based on patient needs and expectations is necessary for the management of ED. The clinician must educate the patient and provide a supportive environment for shared decision making. The management strategy must be supplemented by careful follow-up in order to identify changes in patient health and relationship/emotional status that may necessitate treatment optimisation.
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Carvalheira, Ana; Forjaz, Vera; Pereira, Nuno Monteiro
2014-01-01
Introduction The high effectiveness of phosphodiesterase type 5 inhibitors (PDE5-i) in the treatment of erectile dysfunction (ED) has been demonstrated. However, previous research shows that PDE5-i treatments have high discontinuation rates. Aim The main goals of this study were to (i) characterize the way men use PDE5-i and (ii) analyze the adherence to treatment, identifying the factors that influence PDE5-i use. Methods A total of 148 men with clinical diagnosis for ED who maintained the treatment with PDE5-i for over 3 years were interviewed. Interviews concerning their ongoing treatment were carried out using a standardized questionnaire with quantitative and qualitative items. Main Outcome Measures Physiological measures included the intracavernous alprostadil injection test, associated with penile rigidometry and penile Doppler ultrasound. The qualitative measure included two questions: “Do you use the drug in every sexual intercourse?” and “How do you use the inhibitor?” Results ED causes were classified as venogenic (31%), arteriogenic (23%), psychogenic (18%), iatrogenic (13%), neurogenic (8%), and diabetic (7%). Participation rate was 71.8%. Of the 148 patients studied, 75% claimed not to use PDE5-i in every intercourse. Most used tadalafil (66%), followed by sildenafil (20%), vardenafil (10%), and 4% alternated the type of medicine. Four main categories emerged concerning the factors that determine the intake of PDE5-i in some intercourse situations and not in others: (i) psychological factors; (ii) medication-related factors; (iii) circumstantial factors; and (iv) relational factors. Conclusion The analysis of men's narratives revealed a combination of factors that influence the adherence to PDE5-i. The psychological and medication-related factors were the most prevalent. This study highlighted the importance of taking these factors into account, both at the time of prescription and during the follow-up in order to improve adherence. Carvalheira A, Forjaz V, and Pereira NM. Adherence to phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction in long-term users: How do men use the inhibitors? Sex Med 2014;2:96–102. PMID:25356304
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Hatzichristodoulou, Georgios; Meisner, Christoph; Gschwend, Jürgen E; Stenzl, Arnulf; Lahme, Sven
2013-11-01
Extracorporeal shock wave therapy (ESWT) for treatment of Peyronie's disease (PD) is controversial. To study the efficacy of ESWT by a placebo-controlled, randomized trial. Patients with PD (n=102) were randomly assigned (n=51) to each group (ESWT or placebo). All patients were given 6 weekly treatments. Patients in the ESWT-group received 2,000 shock waves per session, using the Piezoson 100 lithotripter (Richard Wolf, Knittlingen, Germany). Patients in the placebo-group were treated with interposition of a plastic membrane, which prevented any transmission of shock waves. Primary end point was decrease of pain between baseline and after 4 weeks follow-up. Secondary end points were changes in deviation, plaque size, and sexual function. Pain was assessed by a visual analog scale. Deviation was measured by a goniometer after artificial erection using Alprostadil (Viridal®, Schwarz Pharma, Monheim, Germany). Plaque size was measured with a ruler and sexual function assessed by a scale regarding the ability to perform sexual intercourse. Overall, only 45 patients experienced pain at baseline. In the subgroup analysis of these patients, pain decreased in 17/20 (85.0%) patients in the ESWT group and 12/25 (48.0%) patients in the placebo group (P=0.013, relative risk [RR]=0.29, 95% confidence interval: 0.09-0.87). Penile deviation was not reduced by ESWT (P=0.66) but worsened in 20/50 (40%) and 12/49 (24.5%) patients of the ESWT and placebo-group, respectively (P=0.133). Plaque size reduction was not different between the two groups (P=0.33). Additional, plaque size increased in five patients (10.9%) of the ESWT group only. An improvement in sexual function could not be verified (P=0.126, RR=0.46). Despite some potential benefit of ESWT in regard to pain reduction, it should be emphasized that pain usually resolves spontaneously with time. Given this and the fact that deviation may worsen with ESWT, this treatment cannot be recommended. © 2013 International Society for Sexual Medicine.
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Su, Xiaole; Xie, Xinfang; Liu, Lijun; Lv, Jicheng; Song, Fujian; Perkovic, Vlado; Zhang, Hong
2017-01-01
To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI). Systematic review containing a Bayesian network meta-analysis of randomized controlled trials. Participants undergoing diagnostic and/or interventional procedures with contrast media. Randomized controlled trials comparing the active drug treatments with each other or with hydration alone. Any of the following drugs in combination with hydration: N-acetylcysteine (NAC), theophylline (aminophylline), fenoldopam, iloprost, alprostadil, prostaglandin E 1 , statins, statins plus NAC, bicarbonate sodium, bicarbonate sodium plus NAC, ascorbic acid (vitamin C), tocopherol (vitamin E), α-lipoic acid, atrial natriuretic peptide, B-type natriuretic peptide, and carperitide. The occurrence of contrast-induced AKI. The trial network included 150 trials with 31,631 participants and 4,182 contrast-induced AKI events assessing 12 different interventions. Compared to hydration, ORs (95% credible intervals) for contrast-induced AKI were 0.31 (0.14-0.60) for high-dose statin plus NAC, 0.37 (0.19-0.64) for high-dose statin alone, 0.37 (0.17-0.72) for prostaglandins, 0.48 (0.26-0.82) for theophylline, 0.62 (0.40-0.88) for bicarbonate sodium plus NAC, 0.67 (0.54-0.81) for NAC alone, 0.64 (0.41-0.95) for vitamins and analogues, 0.70 (0.29-1.37) for natriuretic peptides, 0.69 (0.31-1.37) for fenoldopam, 0.78 (0.59-1.01) for bicarbonate sodium, and 0.98 (0.41-2.07) for low-dose statin. High-dose statin plus NAC or high-dose statin alone were likely to be ranked the best or the second best for preventing contrast-induced AKI. The overall results were not materially changed in metaregressions or subgroup and sensitivity analyses. Patient-level data were unavailable; unable to include some treatment agents; low event rates; imbalanced distribution of participants among treatment strategies. High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced AKI in patients undergoing diagnostic and/or interventional procedures requiring contrast media. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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SOP conservative (medical and mechanical) treatment of erectile dysfunction.
Porst, Hartmut; Burnett, Arthur; Brock, Gerald; Ghanem, Hussein; Giuliano, Francois; Glina, Sidney; Hellstrom, Wayne; Martin-Morales, Antonio; Salonia, Andrea; Sharlip, Ira
2013-01-01
Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships. The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures. The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included. Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation. © 2013 International Society for Sexual Medicine.
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AB028. Current status of pharmacotherapy for erectile dysfunction
Adaikan, P Ganesan
2016-01-01
The advent of phosphodiesterase type 5 (PDE5) inhibition as oral therapy has significantly revolutionized both clinical and basic research in the area of erectile dysfunction (ED). Much of this progress is due to a better understanding in the last three decades of the various pathophysiological and cellular mechanisms contributing to ED. Apart from the three available PDE5 inhibitors viz., sildenafil, tadalafil and vardenafil globally at the turn of this century, four other PDE inhibitors have joined the armament in recent time; these include avanafil, lodenafil, mirodenafil and udenafil. All seven PDE inhibitors are effective therapies for the treatment of ED in men. There is no significant difference among them with respect to efficacy, safety profile and tolerability. As such, good safety profiles have widened the horizon in patient choice, selectivity and efficacy. With the ease of oral administration and better patient compliance, other measures of the past, including intracavernosal injections and non-pharmacological treatments have been relegated to second-line therapy for most patients with ED. But, PDE inhibitors as first-line oral therapies are effective in about 75% of male patients diagnosed with ED. Intracavernous injection (IC) therapy with PGE1 (alprostadil) for about 10% patient-usage in general is a well-known effective and well tolerated treatment for men with ED. It is also recommended as a second line therapy for ED along with urethral and topical PGE1. Transurethral PGE1 is less effective compared to IC PGE1. Also the transurethral dosage options are 125 to 1,000 µg, while the IC dosage options are 5 to 40 µg. The topical PGE1 (300 µg in 100 mg of the cream) is also less effective compared to IC PGE1. Topical cream is not approved in many countries as yet. Other existing vasoactive agents such as papaverine, and alpha adrenergic blockers and their combinations and the ever increasing number of other agents in the pipeline including nitric oxide donors, guanylate cyclase activators, potassium channel openers and Rho-kinase inhibitors with the potential to overcome some limitations of the existing measures offer significant promise of clinical application in refractory and resistant cases. The TriMix preparations usually contain PGE1, papaverine and phentolamine in formulation compounded in pharmacies. Several clinical studies have also tested the efficacy of yohimbine, L-arginine, cyclic adenosine monophosphate activators, melanocortin-stimulating hormone analogs, endothelin antagonists in addition to vasoactive intestinal polypeptide and calcitonin gene related peptide with variable success rates. Trazodone, a serotonin antagonist and reuptake inhibitor was shown to improve premature ejaculation and erectile function in psychogenic cases of ED. Cloning of inducible nitric oxide synthase has opened a new era in the use of gene therapy for ED and the day for stem cells therapy and autologous penile tissue implants is not too far. Thus, ongoing research worldwide will continue to define new roles for various modalities targeted at specific sites in the erectile pathway and these advances will ultimately enable the clinicians to make the most appropriate therapeutic or other selections for individual patients including possible permanent reversal of organic ED.
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Ozawa, Hikaru; Abiko, Yasushi; Akimoto, Takeshi
2003-01-01
The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)