Intracavernous Injections in Spinal Cord Injured Men With Erectile Dysfunction, a Systematic Review and Meta-Analysis.

INTRODUCTION: Despite improvements in the care of patients after spinal cord injury (SCI), permanent impairment of locomotion, sensation, and autonomic function remains a major hurdle. After the acute stage of injury, recovering sexual function is a high priority. AIM: To review the efficacy of intracavernous injections (ICIs) in men with SCI and to identify prognostic factors affecting the efficacy of ICIs in this population. METHODS: Systematic review of the literature was conducted using the PubMed-Medline, Embase, EBSCO, Web of Science, and Cochrane Library databases. The literature search was restricted to articles published in English, French, and Spanish up to November 2014 using the key words alprostadil, papaverine, moxisylite, alpha-blocking agent, phentolamine, intracavernous injection, spinal cord injuries, paraplegia, quadriplegia, and erectile dysfunction. Studies involving patients with SCI and erectile dysfunction treated with ICIs of alprostadil, papaverine, and α-blocking agents, including retrospective and prospective cohorts, population studies, and randomized controlled trials, were included. MAIN OUTCOME MEASURE: Overall response rate to ICI for erectile dysfunction in patients with SCI. RESULTS: Of 283 studies identified, 23 involved 713 patients with SCI. ICIs resulted in successful erections in 88% of patients (n = 713, 95% CI = 83%-92%). Erections were obtained in 93% of patients (n = 101, 95% CI = 83%-99%) with the combination of papaverine and phentolamine, in 91% (n = 274, 95% CI = 78%-97%) with papaverine alone, and in 80% (n = 119, 95% CI = 64%-90%) with alprostadil. Type of injected drug, doses, level of injury (complete or incomplete), extent of injury, age, time since injury, and persistence or transience of erections were evaluated, but statistical analysis could not identify specific factors predictive of a response to ICI. CONCLUSION: ICIs are an effective treatment of erectile dysfunction in men with SCI. No predictive factor for efficacy could be identified. Studies comparing the response to ICI in upper vs lower motor neuron lesions could improve our understanding of ICI failure.

Perniosis en pacientes pediátricos / Perniosis(chilblains) in pediatric patients

La perniosis es una respuesta anormal al frío, que se manifiesta como lesiones violáceas, edematosas y dolorosas que generalmente afectan a zonas acrales del cuerpo. Es más frecuente en otoño e invierno, y en regiones con clima frío y húmedo. Con frecuencia. los pacientes son mujeres jóvenes, aunque este cuadro también se ha descrito en niños. El curso generalmente es autolimitado, y es suficiente empezar un tratamiento sintomático

Chilblains is an abnormal response to cold, that manifests as painful, purplish, edematous lesions, usually affecting acral sites of the body. It is more frequent in fall and winter, and in regions with cold and damp weather. The patients are usually young women, but this condition has algo been described in children. The course is nearly always self-limited, and only symptomatic treatment is necessary

Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte.

Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple system atrophy (MSA). alpha1-Adrenergic receptors are present in the proximal urethra where impaired relaxation may be responsible for voiding difficulty and a large amount of residual urine. An open study was designed to evaluate whether the blockade of these receptors by prazosin (a nonselective alpha1 blocker) and moxisylyte (an alpha1A-selective blocker) would improve bladder emptying in patients with MSA. Post-micturition residual volumes and clinical symptoms of 49 patients with MSA were evaluated at trial entry and after 4 weeks (prazosin; n=21 and moxisylyte; n=28). The respective means for the prazosin and moxisylyte groups were 38.1% and 35.2% reductions in residual urine volume (P<0.05), and there was lessening of urinary symptoms. Side effects due to orthostatic hypotension were seen in 23.8% of the prazosin group but in only 10.7% of the moxisylyte group. These effects were common in patients with postural hypotension of more than -30 mmHg at trial entry (P<0.05). Modulation of alpha1-receptors may function in the management of lower urinary tract dysfunction in MSA.

Moxisylyte: a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in impotence.

Moxisylyte is a competitive noradrenaline antagonist, acting preferentially on post-synaptic alpha-1 adrenoceptors. It was introduced more than thirty years ago for the treatment of cerebro-vascular disorders and shown more recently effective in the urological field due to its ability to modulate the urethral pressure. Renewal of interest in this drug has been observed in recent years since the demonstration of the possibilities of vasoactive drugs in evaluation and treatment of erectile dysfunctions. Moxisylyte is a prodrug, rapidly transformed into an active metabolite in plasma (Deacetylmoxisylyte or DAM). Elimination of the active metabolite occurs by N-demethylation, sulpho- and glucuroconjugation. The N-demethylated metabolite is sulphoconjugated only. Urine is the main route of excretion. The metabolites of moxisylyte can be determined in biological fluids by various methods using high-performance liquid chromatography. Their pharmacokinetics is dependent on the route of administration. By the oral route, the concentrations of the active metabolite are low, and the glucuroconide of DAM predominates over the sulphates. After intravenous and intracavernous injection, the active metabolite is proportionally higher, the two sulphates are equivalent and in larger amounts than the glucuronide. In the treatment of impotence, intracavernous injection of moxisylyte at 10, 20 or 30 mg can induce an erection adequate for intercourse in most of the patients. Compared to inducing agents such as papaverine and prostaglandin E1, moxisylyte must be considered as a facilitator of male erection, its interest lying in the low rate of adverse effects, either general or local.

Double-blind multicenter study comparing alprostadil alpha-cyclodextrin with moxisylyte chlorhydrate in patients with chronic erectile dysfunction.

PURPOSE: We compared the efficacy and safety of alprostadil alpha-cyclodextrin and moxisylyte chlorhydrate to induce erections adequate for sexual intercourse in a prospective, randomized, parallel double-blind study in patients with erectile dysfunction. MATERIALS AND METHODS: A total of 156 men with erectile dysfunction due to organic, nonorganic and mixed origin was randomized into 2 parallel treatment groups receiving titrations of an individual optimum dose of alprostadil alpha-cyclodextrin or moxisylyte chlorhydrate. Erectile response was measured by the buckling test. A positive test was associated with axial erection rigidity that did not buckle/deform to 1.0 kg. load. The buckling test was repeated every 10 minutes for up to 60 minutes. RESULTS: A total of 56 patients (75%) in the alprostadil alpha-cyclodextrin group and 32 patients (40%) in the moxisylyte chlorhydrate group responded with at least 1 positive buckling test during the office period. Investigators assessed erections after alprostadil alpha-cyclodextrin to be adequate for sexual intercourse in 61 patients (81%) compared to 37 patients (46%) after moxisylyte chlorhydrate. All efficacy parameters in office reached statistical significance of p < 0.001 in favor of alprostadil alpha-cyclodextrin. During self-injection therapy at home 58 patients (85%) reported at least 1 rigid erection after alprostadil alpha-cyclodextrin compared to 37 patients (61%) after moxisylyte chlorhydrate. Patient and partner opinion of treatment achieved statistically significantly better scores in the alprostadil alpha-cyclodextrin group compared to the moxisylyte chlorhydrate group. CONCLUSIONS: Alprostadil alpha-cyclodextrin is significantly more effective than moxisylyte chlorhydrate in producing full penile rigidity in office and at home. Injection related side effects occur with the same frequency but moxisylyte results in more systemic side effects and alprostadil results in more painful and prolonged erections. Patients and partners are significantly more satisfied with alprostadil alpha-cyclodextrin.

Intracavernous pharmacotherapy: comparison of Moxisylyte and prostaglandin E1.

We report in this retrospective study the results obtained with the first two drugs proposed to reduce the relatively high rates of priapism and fibrosis bound to the papaverine intracavernous injections, i.e. the alpha-blocking agent Moxisylyte (Mox), and prostaglandin E1 (PGE1). Each drug was used for auto-injections in 130 patients with a comparable mean follow up (14.8 months with Mox compared to 14.6 with PGE1). PGE1 proved to be significantly more efficacious (good results in 71% of the patients vs 50% with Mox), especially in the arteriogenic patients (respectively 96% vs 46%). Conversely PGE1 induced prolonged erections in significantly more patients (11 vs 1 with Mox), including 2 priapisms, and also induced pain in more patients (12 vs 1 with Mox). The rate of fibrotic nodules and plaques was low (2 and 3 patients). Despite the better tolerance of Mox, its continuation rate was significantly lower than that of PGE1, PGE1 can be the first choice agent in most cases. Mox is mainly indicated in the patients with supersensitivity to the injections and in those with significant pain following PGE1.

[Prolonged use of moxisylyte chlorhydrate (Icavex) by intracavernous self-injections in the treatment of impotence. Evaluation of long-term tolerance]. / Utilisation prolongée de chlorhydrate de moxisylyte (Icavex) en auto-injections intra-caverneuses dans le traitement de l'impuissance. Evaluation de la tolérance à long terme.

Moxisylyte chlorhydrate is a selective alpha-blocker of the post-synaptic alpha 1-adrenoreceptors. It has been used since 1992 for self-injections to induce erection. Tolerance has been studied in open trials in 143 men using 20 mg per intracavernous injection. Among these subjects, 104 were followed for 11 months. Self-administration was performed 7,509 times, i.e. 49.1 injections per subject over a mean period of 307 days. No severe side effects were observed. A total of 1,041 undesirable effects were reported by 90 subjects (75.1%), including mechanical disorders (28.2%) such as pain and burning sensation at injection, hematomas and ecchymoses. Nodules developed in 0.08% of these cases but always regressed. In 71.8% of the cases, the undesirable events was imputable to moxisylyte: dry mouth (2.73%), somnolence (1.9%), sinus congestion (0.71%). No case of priapism was reported. Long-term evaluation showed a reduction in the main undesirable effects with time. This fall off in the mechanical events could be explained by the subjects become for familiar with the technique. Pharmacological effects remain to be analysed. Added to the good tolerance, this result suggests that self-injection can be proposed as a first intention treatment for impotency.

[Treatment of erectile insufficiency]. / Traitement de l'insuffisance érectile.

Impotency, or impaired erectile function, affects approximately 10% of the adult males in France. The psychological consequences can have a major impact not only on the subject's sexual life but also his familial and professional relationships. The task facing the urologists is to carefully evaluate the patient's request for care and adapt treatment not only to the physiological situation but also the patient's psychological and social context. Several approaches have been developed. Search for an aetiology, excepting exceptional cases with a recognized organic origin, is often unsatisfactory due to the multifactor processes involved and the self-sustaining inter-relationship between the psychological impact and the physiological disorder. Sex therapy is aimed at reducing anxiety and helping the couple better understand their sexual relationship. Such behavioural counselling is particularly indicated in absence of organic disorders or as complementary therapy combined with medical or surgical treatment. The pharmacological approach relies on alphablockers or certain psychotropic drugs which have a moderate but real effect when taken orally. Local non-invasive applications of protaglandin E1 can also improve erectile function. The mechanism of intrapenial injections is to release the erectile smooth muscles. The most widely used drugs in France are papaverine, phentolamine and moxisylite as well as prostaglandin E1. Self-injections may be required in certain cases but are abandoned by about half of the patients after one or two months. Vacuum with a mechanical pump can produce a non-physiological erection but is rarely used in France. Surgical repair of arterial or venous disorders can also provide excellent, particularly long-term, results in carefully selected patients. Despite undeniable progress, the treatment of impotency remains a difficult therapeutic challenge, basically due to the large number of casual factors and their complex interactions.

[Changes in urethral pressure after intravenous injection of moxisylyte hydrochloride in urethral instability in women. Preliminary results]. / Evolution des pressions urétrales après injection intraveineuse de chlorhydrate de Moxisylyte dans l'instabilité urétrale de la femme. Résultats préliminaires.

OBJECTIVE: To study the action of an alpha blocker, Moxisylyte hydrochloride, during an intravenous test on the course of urethral pressure in women with urethral instability associated with urethral hypertonia. METHODS: The population consisted of 20 women with a mean age of 38 years, presenting with a clinical disorder of micturition (urinary incontinence: 15 cases, urgency: 17 cases, frequency, 17 cases) present for an average of 4 years and associated with resting urethral pressure variations ranging from 22 to 88 cm H2O (mean: 44.8 cm H2O) and static urethral pressures ranging 72 to 150 cm H2O (mean: 102.5 cm H2O). An urodynamic assessment was performed before and after intravenous injection of Moxisylyte hydrochloride at the dose of 0.5 mg/kg. RESULTS: Moxisylyte hydrochloride induced a significant reduction of urethral pressure variations, ranging from 8 to 42 cm H2O (mean: 21.9 cm H2O) and static urethral pressures, ranging from 47 to 102 cm H2O (mean: 68.8 cm H2O). Treatment was well tolerated in every case. CONCLUSION: These preliminary results need to be completed by a randomized placebo-controlled study to confirm a statistically significant effect of Moxisylyte hydrochloride on urethral pressure stability in women presenting with urethral instability.

The antimigraine effect of ergotamine: a role for alpha-adrenergic blockade?

The hypothesis that alpha-adrenergic receptor blockade accounts for the ability of ergotamine to stop migraine attacks was tested, in migraine patients, in an experimental migraine model based on nitroderivative- induced attacks. In a preliminary single blind, placebo controlled study, thymoxamine, a prevalently post-synaptic alpha adrenergic receptor antagonist, was able to abort migraine attack in 9 out of 10 patients, as opposed to 2 out of 10 by placebo (p < 0.005 Fisher's exact test). In a subsequent randomized, crossover, placebo controlled double blind study, the ability of a selective alpha-1 adrenergic receptor agonist, methoxamine, to block ergotamine antimigraine effect was studied. In 26 patients migraine was induced in two separate tests and then ergotamine was administered once after methoxamine pretreatment and once after placebo; methoxamine was significantly more effective than placebo in blocking antimigraine effect of ergotamine (p = 0.0055 Fisher's exact test). These results support the hypothesis that ergotamine alpha-1 adrenolytic properties may account for its antimigraine effect suggesting that this action takes place outside the blood-brain barrier, since methoxamine can cross it very poorly. Ergotamine target structure could be the trigeminal innervation of the extracranial and/or dural vessels.

[Treatment of impotence with intracavernous auto-injections: moxisylyte diminishes the risks compared to papaverine]. / Traitement de l'impuissance par auto-injections intracaverneuses: le moxisylyte diminue les risques par comparaison avec la papavérine.

The alpha-blocking agent Moxisylyte was tested in auto-intracavernous injections (auto-ICI) in 72 impotent patients. The side-effects were compared to those observed in a group of 34 impotent patients treated with auto-ICI of Papaverine during the same period of time. The Moxisylyte auto-ICI improved 83% of the patients including 68% reporting a complete and durable success. Moxisylyte proved to be safer due to a reduced rate of prolonged erections (1.3% of the patients versus 8.8% with Papaverine) and corporeal fibrosis (1.3% versus 32% with Papaverine). Though less potent than Papaverine, and often seeming insufficient when tested in the office, this type of alpha-blocking agent could be tried in a first time in most candidates to auto-ICI before resorting to Papaverine or Prostaglandin E1 if it fails.

Efficiency and side effects of intracavernous injections of moxisylyte in impotent patients: a dose-finding study versus placebo.

We assessed the efficiency and tolerance of the alpha-blocking agent moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30 mg.) of moxisylyte and a placebo. The erectile response was determined 5, 10, 15, 20 and 30 minutes after each injection. Whatever etiology of impotence and dosage tested, the erectile response induced by moxisylyte was significantly higher than the placebo-induced response. No difference occurred among the 3 doses. In 93% of the patients moxisylyte induced an erectile response, including tumescence in 6, partial rigidity in 16 and complete rigidity in 46. Thus, in 62 of 73 patients (85%) the drug allowed initiation of erection adequate for intercourse. Placebo induced such erection in only 25% of the cases and in 55% there was no response. Tolerance was good and no priapism occurred. Only 4 patients (5%) reported mild pain during injection but erections were never painful, 1 presented with moderate and transient hypotension at the 20 mg. dose and a painless prolonged erection was observed in 1 case after the lowest dose. Drugs such as moxisylyte should be given before less well tolerated drugs.

Adjuvant drug therapy: a review of 30 cases of sacral anterior root stimulator.

Implantation of a sacral anterior root stimulator in spinal cord injured patients must achieve two main goals to maintain a vesicosphincteral balance: complete bladder voiding and correct continence. During the postoperative period, difficulties may arise or persist with either an incontinence due to an insufficient deafferentation with bladder hyperreflexia or an incomplete voiding because of an insufficient contraction of detrusor and/or too high urethral resistances (vesicosphincteral dyssynergia). A third of our patients required specific therapies after implantation to promote interstimulation continence and complete bladder voiding. Regarding continence, adjuvant therapies are effective for bladder hyperreflexia in connection with a too-partial deafferentation. On the other hand, these therapies have little effect on low bladder compliance. In regard to bladder voiding, nonsurgical treatments are equally effective. These treatments (parasphincteral infiltrations, alpha-blockers) must not be permanent, but allow a reharmonizing between expulsive strengths and urethral resistances. Eighty percent of our patients who required adjuvant therapies have been improved significantly. This confirms the efficiency of adjuvant therapy and speaks for patience.

Is the volume injected a parameter likely to influence the erectile response observed after intracavernous administration of an alpha-blocking agent?

In 12 impotent patients with spinal cord injury, we assessed the erectile response induced by intracavernous administration of 20 mg moxisylyte dissolved in 4 different volumes of solvent. We tested successively in each patient 0.4, 0.8, 1.2 ml and the volume usually injected of 2 ml, with a 7-day interval between 2 injections. The reduction in the volume from 2 to 0.4 ml did not thwart the quality of erection obtained by the intracorporeal administration of 20 mg moxisylyte. Indeed, for each erectile parameter (rigidity, abdominopenile angle, length and circumference of the penis), no statistically significant difference arose between the 4 tests. All patients achieved full rigidity. Neither priapism nor prolonged erection occurred. These results suggest that discreet and easily handled small-sized injection pens, containing little solution, could be conceived for autoinjection therapy.

[The combination of oral trazodone-moxisylyte: diagnostic and therapeutic value in impotence. Report of 110 cases]. / L'association trazodone-moxisylite par voie orale: intérêt diagnostique et thérapeutique dans l'impuissance. A propos de 110 cas.

An oral drug treatment was prescribed systematically for one month in 110 unselected patients suffering from impotence: Tradozone (75 mg/day)+Moxisylite (180 mg/day) daily, or at higher doses if possible, and Trazodone (25 mg/day)+Moxisylite (60 mg/day) one hour before any sexual intercourse. Adverse effects were uncommon (6.3%). Satisfactory sexual activity was restored in 28% of cases and an improvement in spontaneous erections was obtained in 42% of cases. No improvement was observed in 30% of cases. This oral drug test therefore presents 3 advantages: a) it facilitates the diagnosis and treatment of impotence by eliminating moderate forms of psychogenic impotence, b) it reduces both the morbidity and cost of investigation of impotence by reducing the number of tests performed, c) it emphasizes the role of oral treatment in impotence. In conclusion, this oral drug test should be used because of its simplicity, safety and real efficacy. The current objectives of this test are to improve the efficacy of oral treatment as a result of pharmacological progress.