Clinical conversations: intraurethral alprostadil (MUSE). Interview by Patricia Bates.
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Alprostadil↗
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Priapism after transurethral alprostadil.
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Alprostadil↗
Intestinal colic and diarrhea as side effects of intravenous alprostadil administration.
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Colic↗
Effects of intravenous prostaglandin E1 on arterial compliance: a randomized controlled trial.
BACKGROUND: Prostanoids are in widespread use for the treatment of critical limb ischemia and are suggested to improve arterial compliance. However, dose- and time-dependency of these drug effects are indeterminate. We investigated the influence of intravenous application of prostanoids on arterial compliance parameters in patients with critical limb ischemia due to peripheral artery disease (PAD). PATIENTS AND METHODS: We included 82 consecutive patients with PAD Fontaine stage III and IV in a patient-blinded, randomized controlled trial. Patients were randomly assigned to either single dose intravenous treatment with 40 microg (n = 29) or 60 microg (n = 27) of Alprostadil (PGE1) in 250 ml 0.9% saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26). Large and small artery compliance was measured by peripheral pulse contour analysis at baseline, at one hour during intravenous infusion of Alprostadil, immediately after and 24 hours after the end of the infusion. For study purposes the patients received Alprostadil only once during the observation period of 2 days. RESULTS: Large artery compliance, blood pressure, heart rate and cardiac output were unaffected by PGE1 administration irrespectively of drug-dosage or time interval. Small artery compliance increased at 1 hour during intravenous application of Alprostadil (40 microg Alprostadil p = 0.001; 60 microg Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to +100%) after administration of 40 microg Alprostadil and median +32% (IQR -11% to +88%) after 60 microg Alprostadil (p = 0.5). Immediately after the end of Alprostadil infusion small artery compliance decreased to baseline levels. CONCLUSIONS: Prostaglandin E1 causes a significant improvement of small artery compliance during the time of intravenous application. However, this effect rapidly diminishes after the end of administration and no dose-dependency between 40 microg and 60 microg Alprostadil is observed.
Adaptation, Physiological↗
Use of medications for erectile dysfunction in the United States, 1996 through 2001.
PURPOSE: 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. RESULTS: 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. CONCLUSIONS: 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.
Adolescent↗
Short-term treatment with prostaglandin E1 analogue has long-term preventive effects on intimal thickening in balloon-injured rat carotid arteries.
We examined effects of a prostaglandin E1 analogue alprostadil on intimal thickening and arterial remodeling in balloon-injured rat carotid arteries. Right common carotid arteries were balloon-injured, and their left counterparts were sham-operated (uninjured). Rats were given alprostadil (0.3 microgram/kg/min, continuous subcutaneous (s.c.) infusion) or vehicle for 1 week after the injury and sacrificed at 4 weeks or 8 weeks. Segments of common carotid arteries corresponding to balloon-injured and uninjured sites were excised and subjected to elastica van Gieson staining. Cross-sectional areas were measured by computed planimetry. Alprostadil prevented intimal thickening at both 4 and 8 weeks. In addition, alprostadil prevented the increase in intimal area/area surrounded by external elastic lamina at both 4 and 8 weeks. Alprostadil had no effects on body weight, heart rate, or systolic blood pressure. Our study demonstrated that alprostadil administered only for the initial 1 week had long-term (up to 8 weeks) preventive effects on intimal thickening. Alprostadil may be useful to prevent restenosis after balloon angioplasty.
Alprostadil↗
Erectile dysfunction.
Erectile dysfunction (ED) is a common condition and can usually be managed pharmacologically, with drugs delivered by intracavernosal injection (ICI), transurethrally or orally. The cardiovascular status of the patient and his overall fitness for renewed sexual activity must be assessed before treatment for ED is initiated. The efficacy of sildenafil is related to the extent and severity of ED, and is significantly reduced in patients with severe vasculogenic ED, ED associated with diabetes and after radical prostatectomy. Alprostadil (prostaglandin E1) is the drug of first choice in patients treated with ICI; it is effective in 72.6% of men with ED and is associated with a low risk of priapism and cavernosal fibrosis. Transurethral alprostadil is significantly less effective than alprostadil ICI, producing improved erections in 30%-40%, but rigid erections in only 10%, of men with ED. There is Level II evidence that: alprostadil ICI is an effective treatment for ED papaverine ICI is associated with a high risk of cavernosal fibrosis and priapism papaverine ICI should be restricted to informed patients refractory to treatment with alprostadil ICI transurethral alprostadil is less effective than alprostadil ICI sildenafil is an effective treatment for ED.
Alprostadil↗
Impact of introduction of sildenafil on other treatment modalities for erectile dysfunction: a study of nationwide and local hospital sales.
We assess the impact of introduction of sildenafil on alprostadil injection and penile implant surgery for the treatment of erectile dysfunction (ED) at our institution and in Taiwan. The data of national sales of sildenafil, alprostadil injection and penile implant were provided by industry companies. In the meanwhile, we analyzed the users of the above-mentioned three treatments at our institution. The national sales of sildenafil grew 136% from 0.8 million tablets in 1999 to 1.6 million tablets in 2002, while those of alprostadil injection dropped 33% after the marketing of sildenafil and of penile implant dropped 40% after the marketing of alprostadil injection and sildenafil. The market share of drugstores for sildenafil rose from 41% in 1999 to 72% in 2002. The trend of sales of sildenafil at our institution was similar to that of national sales from hospitals. Mean age of the sildenafil new users was becoming younger in the past 4 y (P<0.001). Of the new users of alprostadil injection and the recipients of penile implant, the commonest age group shifted from the range of 60-69 y before the launch of sildenafil to that of over 70 y after (P<0.05). In conclusion, the introduction of sildenafil has prompted more men as well as younger men with ED to seek treatment. Part of the roles of alprostadil injection and penile implants in this field are substituted by sildenafil and the commonest age group of their users becomes older than before.
Adult↗
Efficacy evaluation of prostaglandin E1 against placebo in patients with progressive systemic sclerosis and significant Raynaud's phenomenon.
BACKGROUND: Raynaud's phenomenon, due to connective tissue diseases, is difficult to treat successfully. Symptomatic improvement has been reported using nifedipine or iloprost, but adverse side effects may limit their use. The purpose of this study was to examine the effects of PGE1 (Alprostadil) in patients with scleroderma and severe Raynaud's disease. METHODS: Twelve females, aged 50-67 years, were included in the study with six of them receiving a 3-hour infusion of alprostadil at the standard dosage of 60 micrograms in 250 cc of physiological infusion for six consecutive days and the remaining six receiving placebo (250 cc of physiological infusion administered in the same manner). RESULTS: After infusion, blood flow, digitally measured by telethermography was increased only in patients treated with alprostadil. The number, frequency and severity of attacks recorded were reduced only in patients treated with alprostadil. No side effects were recorded during and after the infusion. CONCLUSION: In conclusion, alprostadil is effective in the management of Raynaud's phenomenon, due to scleroderma.
Alprostadil↗
Impact of selective prostaglandin E1 treatment on graft perfusion and function after liver transplantation.
BACKGROUND/AIMS: In several clinical trials, the prophylactic application of prostaglandin E1 did not demonstrate a significant effect on incidence of primary graft nonfunction after liver transplantation. The aim of this study was to evaluate the effect of a selective prostaglandin E1 treatment in liver transplant patients with initially compromised perfusion and thereby depressed early posttransplant graft function. METHODOLOGY: A total of 142 patients were enrolled in this study. In all of them, duplexsonography was performed daily to generally assess patency of allograft vessels and to specifically calculate the resistive index of the hepatic artery. Intravenous therapy with a prostaglandin E1 analogue (Alprostadil, 0.5 microg/kg/h) was initiated in 67 patients after determination of a primarily elevated (>0.75) and posttransplant increasing resistive index of the hepatic artery that was associated with continuously elevating aminotransferases. RESULTS: After initiation of treatment, the arterial resistive index decreased significantly from 0.83+/-0.1 to 0.72+/-0.1 on the first day of application (P<0.05). Primarily elevated serum levels of aspartate aminotransferase (AST: Alprostadil: 890+/-180 IU/L: CONTROL: 375+/-98 IU/L) and alanine aminotransferase (ALT: Alprostadil: 850+/-178 IU/L, CONTROL: 310+/-79 IU/L) decreased significantly and reached values comparable to the control group after three days of therapy (AST: Alprostadil: 190+/-40 IU/L, CONTROL: 150+/-45 IU/L ALT: Alprostadil: 280+/-57 IU/L, CONTROL: 180+/-50 IU/L) (P<0.05). Only 2 grafts with initial compromised perfusion and function (3%) developed primary graft nonfunction. CONCLUSIONS: Prostaglandin E1 seems to be effective in ameliorating ischemia-reperfusion injury to the liver in patients with elevated arterial vascular resistance and early depressed graft function after liver transplantation. Duplexsonography in combination with graft function are useful tools for indicating and monitoring treatment.
Adult↗
Functional and radiologic evidence of vascular communication between the spongiosal and cavernosal compartments of the penis.
OBJECTIVES: To investigate the possible communication of the glans penis and corpus spongiosum with the corpora cavernosa. METHODS: We performed a functional and anatomic study in men with erectile dysfunction. The functional study consisted of the injection of alprostadil (10 to 20 micrograms) into the glans in 17 men while recording intracavernosal pressure (ICP). Once the ICP response had stabilized, patients received a second injection of alprostadil by direct intracavernosal (IC) administration. For the anatomic study, a spongiogram was performed in 5 patients by the injection of radiologic contrast into the glans. RESULTS: Injection of alprostadil into the glans caused tumescence of the glans and corpus spongiosum, followed by tumescence of the corpora cavernosa with an increase in ICP from 9 +/- 2 mm Hg (mean +/- SD) at baseline to a peak response of 50 +/- 25 mm Hg. Subsequent IC injection of alprostadil, on average, increased ICP by only 5 mm Hg (a 15% increase) above the response to injection in the glans. The spongiogram demonstrated drainage of the glans into the deep dorsal vein, as well as drainage of the spongiosum into the circumflex veins, which in turn drained into the deep dorsal vein. Filling of the corpora was also visualized, suggesting that it occurred in a retrograde manner, through the draining venules. CONCLUSIONS: Our study demonstrates that injection of alprostadil into the spongy tissue of the glans can provoke erection of the corpora cavernosa, and that common channels for the drainage of the glans, corpus spongiosum, and corpora cavernosa are most likely the route for drug transfer from the spongiosal to the cavernosal compartment.
Humans↗
Effect of sildenafil in cavernous arteries of patients with erectile dysfunction.
INTRODUCTION: Sildenafil citrate is a type 5 phosphodiesterase inhibitor, which has demonstrated excellent results in the treatment of erectile dysfunction. The effect of sildenafil citrate in the cavernous arteries of patients with erectile dysfunction has not been established yet. The objective of this study was to assess the effect of sildenafil citrate in the cavernous arteries of patients with erectile dysfunction, following an intracavernous injection of alprostadil. MATERIALS AND METHODS: 29 male patients, with mean age of 53.8 years (32 to 75 years), were prospectively evaluated. The mean time with complaint of erectile dysfunction was 50.5 months (6 to 168 months). Each patient was his own control. Patients underwent a measurement of peak systolic velocity before and after use of sildenafil citrate associated with 5 micrograms of alprostadil, through ultrasonic velocitometry Knoll/MIDUS system. In the interval between measurements, approximately 15 days, patients used 3 tablets of sildenafil at home with their partners. RESULTS: Using only 5 mcg of alprostadil, average peak systolic velocity was 23.9 cm/s, and when associated to 50 mg of sildenafil it was 24.8 cm/s. Despite the increase in the flow rate caused by sildenafil, the difference was not statistically significant, Z calculated = - 0.695 NS (Wilcoxon test). Twenty one of the 29 patients (72.4%) showed global improvement in sexual performance with the use of sildenafil citrate at home. There was not a statistically significant correlation between the global response to sildenafil citrate and the increase in the peak systolic velocity. CONCLUSION: We concluded that, even though the use of 50 mg of sildenafil citrate associated with 5 mcg of alprostadil provides an increase in the peak systolic velocity of the cavernous arteries, there was no statistic difference in relation to alprostadil alone. There was no correlation between the global response to sildenafil and the increase in the peak systolic velocity.
Journal Article↗
Prostaglandin E1 analog inhibits the microglia function: suppression of lipopolysaccharide-induced nitric oxide and TNF-alpha release.
Release of nitric oxide and TNF-alpha, a toxic cytokine, have been reported to accelerate neuronal damage under several pathological conditions, such as trauma or ischemia in the central nervous system. In the present study, we tested the effect of alprostadil alfadex, a prostaglandin E1 analog, on cultured microglia from the rat spinal cord. The cultured microglia were exposed to lipopolysaccharide (LPS) (100 ng/ml), an endotoxin, for 24 h, then the released nitric oxide and TNF-alpha in the culture media was analyzed. The released nitric oxide was detected by the Griess reaction and released TNF-alpha was measured using ELISA method. The LPS-induced nitric oxide release was inhibited by the simultaneous addition of alprostadil alfadex in a dose-dependent manner (0.1-100 microM). The LPS-induced TNF-alpha release was also inhibited by alprostadil alfadex addition (0.1-100 microM). The IC50 values of alprostadil alfadex on nitric oxide and TNF-alpha release were about 1 and 10 microM, respectively. These results suggest that prostaglandin E1 possibly protects spinal cord neurons from several types of neurodegenerative damage, not only via increased blood supply, but also via inhibition of pathological immunoreactions of activated microglia.
Alprostadil↗
Alibra (VIVUS).
VIVUS is developing a combination therapy for the potential treatment of impotence consisting of alprostadil and prazosin (an alpha-adrenoceptor blocker) for delivery via its transurethral MUSE system. The therapy is being developed as an alternative to MUSE-alprostadil, and the company believes the prazosin component has the ability to reduce the dose of alprostadil necessary, and hence reduce associated pain. In addition, the mechanism of action of prazosin may be more efficacious in some individuals [2730761. By October 1998, the combination was in phase III trials, which were completed by September 1999 [3015441, [338753]. VIVUS submitted an NDA to the US FDA in December 1999 [319367], [344214] and in May 2000, the company filed for marketing authorization in Europe 13687511. In October 2000, the company was still awaiting regulatory approval from the FDA and the EMEA 1384823]. The company subsequently withdrew its NDA in the US. VIVUS Inc have also now withdrawn their application to the FDA and the EMEA for the alprostadil/prazosin MUSE combination product 1394552]. The company is still in discussion with these authorities regarding the application. Abbott Laboratories has exclusive rights for MUSE-alprostadil and Alibra in select markets, including Europe, Japan, Australia, New Zealand, and South and Central America [371435].
Adrenergic alpha-Antagonists↗
[A new approach to raising the efficiency of drug therapy for erectile dysfunction].
AIM: To try combined treatment of erectile dysfunction with viagra and alprostadil in case of failure of their monotherapy; to compare effectiveness of viagra in dynamics of treatment, in various doses and dose adjustment. MATERIAL AND METHODS: 82 patients with ED of different genesis received a course of intracavernous injections of alprostadil followed by a course of viagra; 25 patients received combined treatment with alprostadil and viagra. Each course lasted for 3 months. Viagra efficiency was also assessed in long-term use (12 months) and different initial doses (50 or 100 mg). RESULTS: Monotherapy with alprostadil or viagra was effective in 73.2 and 75.6% patients, respectively. Their combination was more beneficial--88.0%. When used for a long time, viagra lost efficiency in psychogenic ED by 17.7%, in organic ED--by 16.9%. In an initial viagra dose 50 mg efficiency reached 70.3%, 100 mg--80.0%. CONCLUSION: Combined treatment of ED is a method of choice in monotherapy failure and in severe ED. Lowering of viagra efficiency in long-term administration may be explained by disappearance of placebo effect.
Adult↗
The effect of prostaglandin E1 on nailfold capillary blood pressure and red blood cell velocity in humans.
PGE(1) or PGI(2) acutely increase total skin perfusion in healthy volunteers. This study investigated whether skin nutritive perfusion and capillary pressure were increased by acute infusion of PGE(1). In a double blind randomised placebo controlled study the effect of Alprostadil (PGE(1), Prostavasin, intra-venous, infusion rate: 0.38 microg/h/kg,) on skin nailfold capillary blood pressure (CP) and capillary red blood cell velocity (CBV) was investigated in 16 healthy volunteers (placebo: 5 male, 3 female, age: 27.7, range: 22-29 years; Alprostadil: 5 m, 3 f, age 27.1, 22-38 y), using the electrical impedance servo nulling technique and spatial shift alignment method, respectively. Initial finger tip temperature, systemic blood pressure, heart rate, CP, capillary pulse pressure amplitude (CPPA) and CBV showed no significant differences between the two groups (placebo: 23.6 +/- 3.0 degrees C, 123 +/- 13/83 +/- 5 mmHg, 63 +/- 11 beats/min, 15.6 +/- 3.9 mmHg, 1.5 +/- 1.8 mmHg, and 425 microm/s (290-800); Alprostadil: 23.4 +/- 2.7 degrees C, 121 +/- 9/82 +/- 10 mmHg, 65 +/- 9 beats/min, 14.4 +/- 3.7 mmHg, 1.8 +/- 1.3 mmHg, and 680 (140-1090 microm/s)). Twenty minute infusion with either Alprostadil or placebo had no significant effect on any of the parameters measured. Thus, in healthy volunteers, skin capillary blood pressure, capillary pulse pressure amplitude and capillary blood velocity are unaltered by acute administration of PGE(1) at ambient temperatures.
Adult↗
[A role of endothelin 1 in the pathogenesis of thromboangiitis obliterans (initital news)].
BACKGROUND: [corrected] Etiology and pathogenesis of thromboangiitis obliterans, an uncommon disease, but connected with high risk of leg amputation, is still unknown. Genetic predisposition and inconvenient factors of environment, especially nicotine, could initiate an immunological process, which evokes endothelial dysfunction. In histological preparation inflammation and thrombus are observed. Endo-thelin-1 could affect these processes. It is a strong vasa-constrictor and has a wide spectrum of biological activity, often opposed to effect of prostacycline analogs. The aim of study was a role of endothelin-1, antielastin antibodies and selectin P, L, E in the pathogenesis Buerger's disease and influence of alprostadil on these parameters. MATERIAL AND METHODS: We examined 10 patients with Buerger disease in the active phase, which were divided in two subgroups. Four persons with necrosis of toes were in the first subgroup, and six patients with rest pain but without trophic changes in the second subgroup. 13 healthy persons composed the control group. Index of antielastin antibodies, concentration of endotehlin-1, selectin P, L and E were measured in venous and arterial serum. These parameters by patients were determined twice: before and after 10-days treatment with alprostadil 20-40 microg per day. Concentration of endothelin-1, selectins and index antielastin antibodies were measured by enzyme-linked immuno-sorbent assay. RESULTS: We observe increase in endothelin-1 concentration by persons with necrosis of toes compared to patients without these changes (p=0.024) and to control (p=0.022). In the subgroup I index of antielastin antibodies IgA was higher than in control group (p=0.020). After alprostadil treatment endothelin-1 concentration, antielastin antibodies index was not statistically significant compared to results before treatment or control group. We observed correlation between concentration of endo-tehlin-1 before treatment and index of antielastin antibodies IgG (p=0.0475). We observed significant diffrance of concentration of selectin P, L and E compared to control (p=0.038). Especially we noticed higher concentration of selectin P (p=0.001) than in control group. The after treatment reduction of concentration was only for selectin L statistically significant (p=0.038). CONCLUSION: 1. Plasma endothelin-1 level play a role in the exacerbation of clinical symtpoms of thromboangiitis obliterans. 2. Endothelial injury is connected with increase in concentration of selectin P in patient's serum. 3. Alprostadil didn't influence on concentration of endothelin-1 in these patients.
Adult↗
Our experience with pharmacological erection treatment of erectile dysfunction.
Administration of vasoactive drugs intracavernously is a well-known easily used and inexpensive alternative in treatment of a certain group of patients with erectile dysfunction. There are a few drugs used for this purpose, but we prefer papaverine as the first choice because it is easily available and inexpensive in our country. We used alprostadil only in nonresponders to papaverine or if there was any complication with papaverine. We present a series of 69 patients, 24 with psychogenic (34.8%), 27 with organic (39.1%), and 18 (26.1) with mixed etiology of erectile dysfunction, treated with intracavernous self-injection therapy. Mean follow-up of the patients was 13.6 months (7-30 months). In this study, 3,430 papaverine and 780 alprostadil injections were performed in 56 and 13 patients, respectively. In 75% of the papaverine injections and in 83% of the alprostadil injections, erections were achieved sufficient for sexual intercourse. During the follow-up, there were not any abnormal alterations in liver function tests. The main complaint of the patients who used papaverine was a burning sensation (98%) during administration of the drug, which did not last more than 1 minute. Of 13 patients in the alprostadil group, 56.9% of the patients complained mainly of discomfort during erection. We concluded that intracavernous therapy is a good and inexpensive option in the management of erectile dysfunction in carefully selected patients.
Adult↗