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Purpose: We examined whether patients are appropriately screened for previous prolonged erections or priapism and counseled about trazodone complications, specifically prolonged erections and priapism, prior to trazodone treatment., Materials and Methods: We identified patients under the age of 50 on trazodone as of February 27, 2019 at the VA New Jersey Health Care System. Patients were asked about information provided to them prior to medication initiation, occurrence of prolonged erections/priapism, and reporting rate of side effects., Results: Two hundred and twenty nine out of five hundred and twenty four male patients agreed to participate in the study. Forty three out of two hundred and twenty nine of patients were informed about the side effects of prolonged erections and 37/229 of patients were informed of risk of priapism prior to treatment. Only 17/229 of patients were asked if they had had any episodes of prolonged erection or priapism in the past. Eighteen patients developed prolonged erection while taking trazodone. Only 5/18 patients who had developed prolonged erections informed their physicians., Conclusions: Only a fraction of patients were properly screened for previous prolonged erections or priapism and properly informed about the side effects of trazodone. Urologist should better educate trazodone prescribers, such as family medicine and psychiatric colleagues, regarding the side effects of trazodone. It is imperative that prescribing physicians appropriately screen and educate patients prior to trazodone initiation and instruct patients to report any treatment side effects to avoid potential long-term adverse outcomes., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

The use of natural substances for the treatment of diseases or injuries is an ancient practice of many cultures. According to folklore, natural aphrodisiacs may help to raise libido and increase desire. The supposed aphrodisiacs mainly include a plethora of preparations of plants, among other substances. However, the real boundary between myth and reality has not been established yet in most cases and such boundaries must be drawn by scientific methods. A growing interest of the scientific community has been focused on animal venoms, especially those from arthropods, i.e. spiders and scorpions, which cause priapism, a prolonged and painful erection. This review highlights the studies that have been performed with venoms and toxins from arthropods known to cause priapism, among other toxic symptoms, pointing out some pharmacological approaches for better understanding this effect. To date, the venom of some spiders, mainly Phoneutria nigriventer, and scorpions, such as the yellow South American scorpion Tityus serrulatus, among others, have been known to cause priapism. Since erectile dysfunction (ED) is a growing health problem in the world, more common in patients with vascular diseases as diabetes and hypertension, the use of animal venoms and toxins as pharmacological tools could not only shed light to the mechanisms involved in erectile function, but also represent a possible model for new drugs to treat ED. Unfortunately, attempts to correlate the structure of those priapism-related toxins were unfruitful. Such difficulties lie firstly on the poor data concerning purified priapism-related toxins, instead of whole venoms and/or semi-purified fractions, and secondly, on the scarce available primary sequences and structural data, mainly from spider toxins. It has been shown that all these toxins modify the sodium (Na(+)) channel activity, mostly slowing down its inactivation current. Improving the knowledge on the tertiary structure of these toxins could provide a key in the search of a new drug for ED treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In the current study, the putative cDNA for PnTx2-6 toxin of the Phoneutria nigriventer spider venom was cloned and expressed as tioredoxin fusion protein in the cytoplasm of Escherichia coli. The fusion protein was purified from the bacterial extracts by combination of immobilized Ni-ion affinity and gel filtration chromatographies. Then, it was cleaved by enterokinase and the generated recombinant PnTx2-6 (rPnTx2-6) was further purified by reverse-phase HPLC. Likewise the native toxin purified from the spider venom, rPnTx2-6 potentiates the erectile function when injected in rats. This result indicates that the production of functional recombinant PnTx2-6 might be an alternative to provide this basic and valuable tool for study, as well as for further understanding such complex physiological system, including its correlation with the central nervous system and local tissue factors., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Prolonged erection and priapism are common complications following intracavernosal injection of vasoactive agents in the management of erectile dysfunction. It is usually treated by intracorporeal drainage and irrigation with sympathomimetic agents. There is no established oral therapy . To study the effect of oral terbutaline on prolonged erection following intracavernosal injection of vasoactive agent, a controlled randomized study was done in 68 patients. Detumescence was achieved in 42 and 15% of the cases with oral terbutaline and placebo, respectively. Results of this study suggest that an initial trial with oral terbutaline for pharmacologically induced prolonged erection may be successful.

Objectives: To assess magnetic resonance imaging (MRI) combined with artificial erection for local staging of penile cancer., Methods: We compared local clinical, MRI plus artificial erection, and pathologic staging in 9 cases of penile cancer. Erection was obtained by injecting 10 microg prostaglandin E1 into the corpora cavernosa. T1-weighted and T2-weighted MRI with and without contrast was obtained using a phased array coil. Local treatment was based on tumor location and extent, as defined by the clinical and MRI findings., Results: The histologic diagnosis was squamous cell carcinoma in 8 patients and sarcoma in 1. The MRI and pathologic staging coincided in 8 of 9 patients. MRI, clinical, and pathologic staging coincided in 5 patients: 4 had Stage T2 and 1 had Stage T1 disease. In 2 patients, the MRI and pathologic stage was T2, but the clinical stage differed. Another patient had Stage T2 clinically but T3 by MRI and pathologic staging. In the last patient, none of the stages coincided (clinical Stage T1, MRI Stage T0, and pathologic Stage Tis). The only complication during the procedure was that 1 patient developed priapism after prostaglandin injection, which was relieved by evacuation of the corpora cavernosa., Conclusions: To our knowledge, this is the first study to use artificial erection with MRI to stage local penile cancer. The method appears promising for local staging of penile cancer, but additional studies are necessary to confirm its utility.

Sildenafil, in nanomolar serum levels, is an effective phosphodiesterase type 5 inhibitor, and facilitates penile erection only during sexual stimulation. However, there is limited information on the pharmacological activity of this agent when tissue levels approach millimolar concentrations following intracavernosal injection. The aim of this study was to investigate whether sildenafil causes penile erection in the absence of active neurogenic input. Organ bath preparations of rabbit penile cavernosal tissue strips were contracted with 1 microM phenylephrine and exposed to increasing concentrations of sildenafil in the absence or presence of the nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME; 0.6 mM). Sildenafil caused dose-dependent relaxation of rabbit cavernosal smooth muscle at high concentrations (>0.1 microM) with little or no effect at concentrations below 0.1 microM. The addition of L-NAME did not affect this response. In a separate protocol, sildenafil dose response determinations were performed in the presence of the guanylyl cyclase inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ; 3 microM) or vehicle (50% dimethyl sulfoxide [DMSO]). Relaxation to sildenafil in the presence of DMSO was significantly enhanced relative to sildenafil alone. ODQ treatment partially attenuated relaxation to sildenafil, but failed to completely inhibit the response. In cavernosal tissue strips, sildenafil elevated basal cyclic guanosine monophosphate (cGMP) levels twofold (0.54 vs. 1.10 pmol/mg prot). To further investigate these observations, anesthetized rabbits were injected intracavernosally with sildenafil (0.3-1.3 mg). In the absence of pelvic nerve stimulation, the magnitude and duration of the intracavernosal pressure increased in a dose-dependent fashion in response to sildenafil, approaching the systemic arterial pressure at higher doses. Intracavernosal administration of L-NAME, at doses that inhibited pelvic nerve stimulated penile erection, did not alter the response to intracavernosal sildenafil at 1.3 mg. Sildenafil, at the doses tested, did not significantly change the systemic arterial pressure. These data suggest that intracavernosal sildenafil, at tissue levels approaching millimolar concentrations, can cause relaxation of vascular smooth muscle and penile erection by a novel mechanism independent of the classical NO/cGMP pathway.

Objectives: To examine the effects of Tityus serrulatus scorpion venom (TSV) on human corpus cavernosum (HCC) using a bioassay cascade. Priapism is occasionally observed in scorpion envenomation, mostly in children., Methods: HCC strips were suspended in a cascade system and superfused with aerated and warmed Krebs' solution at 5 mL/min. Noradrenaline (3 micromol/L) was infused to induce a submaximal contraction of the HCC strips. The release of cyclooxygenase products was prevented by infusing indomethacin (6 micromol/L)., Results: N(omega)-nitro-L-arginine methyl ester (10 micromol/L; n = 10) increased the tone of the preparations and significantly reduced (P <0.01) the acetylcholine (ACh) and TSV-induced relaxations. Subsequent infusion of L-arginine (300 micromol/L) partially reversed the increased tone and significantly restored the relaxations induced by TSV and ACh (P <0.01). The soluble guanylyl cyclase inhibitor ODQ (10 micromol/L; n = 8) markedly reduced (P <0.01) the relaxations induced by TSV, ACh, glyceryl trinitrate, and bradykinin. 7-Nitroindazole (10 micromol/L; n = 8) inhibited the relaxations induced by TSV by 84% (P <0.01) and also caused small, but significant, reductions in the ACh and bradykinin-induced HCC relaxations (P <0.05). Atropine (1 micromol/L; n = 6) abolished the relaxations evoked by ACh (P <0.01), but had no effect on those elicited by TSV. Tetrodotoxin (1 micromol/L; n = 6) abolished the relaxations induced by TSV (P <0.01) and also reversed the established TSV-induced relaxation (n = 4)., Conclusions: Our results indicate that TSV relaxes HCC through the release of nitric oxide from nonadrenergic, noncholinergic (NANC) nerves. The elucidation of the mechanism responsible for the TSV-induced relaxations might be useful for a better understanding of the development of priapism in cases of scorpion envenomation.

All forms of pharmacological therapy result in a relaxation of the corporeal smooth muscle. Intracorporeal injection of vasoactive drugs was introduced around 15 years ago and still is the most effective therapy in erectile dysfunction. Resulting in a consistent success rate of 70-80% this form of therapy will find numerous applications, even after the introduction of effective oral agents such as sildenafil. Prostaglandin E1 and--less frequently used--the combination of papaverine and phentolamine are the mainstay of intracorporeal injection therapy. Intraurethral prostaglandin (MUSE) has recently become available and is somewhat less effective than injection therapy. Externally applied drugs (nitroglycerin paste on the penile shaft and minoxidil solution on the glans penis) have not succeeded in the long run. Vacuum erection devices represent a form of physical topical therapy that is very versatile and also effective but rather infrequently applied.

Purpose: We report a case of prolonged nocturnal penile tumescence (NPT) caused by the antiallergic agent epinastine., Methods/results: We measured NPT using Rigiscan-Plus (DacoMed, Minneapolis, MN, USA) with or without the patient having taken epinastine., Conclusions: Considering its pharmacological effects on cyclic nucleotides, epinastine may have an effect on erectile function.

Using papaverine, papaverine/phentolamine, or prostaglandin E1 (PGE1), intracavernosal pharmacotherapy has been successful in treating erectile dysfunction. The limiting factor of using these medicines is intracorporeal fibrosis with the first two and a high cost with PGE1. Our experience with intracavernosal therapy in patients with impotence secondary to neurogenic disease has included 35 men, 30 of whom are spinal cord injured, 3 after radical prostatectomy, 1 with multiple sclerosis, and 1 with lower extremity weakness after surgery. Patients ranged in age from 22 to 59 years, with an average of 36.3 years; mean follow-up was 13.8 months. Intracavernosal therapy has been performed with a tri-mixture of papaverine hydrochloride (smooth muscle relaxant), phentolamine mesylate (alpha-adrenergic blocking agent) and alprostadil (PGE1- a vasodilator and smooth muscle relaxant). Of the patient population, all 35 patients were able to have adequate erections for sexual relations with minimal complications. Acting synergistically, the ingredients promote erectile activity using small doses and without a significant incidence of priapism or fibrosis. Techniques of injection, dosing and followup are discussed.

A group of 170 impotent men achieved usable erections during a 26-month period with a combination of papaverine, phentolamine and prostaglandin E1 (triple-drug therapy) injected intracorporeally. Of the patients 146 elected to enter a pharmacological erection program using this combination. Patient age ranged from 24 to 85 years and the average duration on the program was 11.2 months. Average injection volume was 0.36 cc per injection (range 0.1 to 1). Among those patients managed by our nurse clinician, only 3 episodes of priapism were encountered (1.7%). Scarring was documented in 7 of 170 patients (4.2%) 1 week to 21 months after starting the injections. Pain was encountered in 6 of 170 patients (3.5%). A superior dose response coupled with a low incidence of priapism, pain and scarring have led us to use triple-drug therapy as our agent of choice in the pharmacological management of erectile dysfunction.

Treatment with the antidepressant trazodone has been associated with the occurrence of prolonged penile erection and priapism. To evaluate the effect of trazodone on erection we monitored the periodic physiological sleep-related erections in 6 healthy volunteers in a double-blind crossover study comparing the effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In addition, to determine the effects of trazodone on the neurovascular control of penile smooth muscle we performed in vitro studies on corpus cavernosum tissue obtained from patients undergoing penile prosthesis implantation. Trazodone significantly increased the total interval of nocturnal erectile activity, while trimipramine had no effect. During the high dose treatment (nights 4 and 5) the average duration of erectile activity per night with placebo was 158 +/- 41 minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for night 5. During trazodone treatment the erectile activity per night was significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86 during night 5 (p less than 0.01). Analysis of the erectile activity in relation to the rapid eye movement sleep period during which erectile activity usually occurs revealed that the detumescence phase of erection, under sympathetic control, was significantly prolonged an average of 2.4 times by trazodone compared to placebo (p less than 0.05). In vitro, trazodone at concentrations comparable to those reached in plasma significantly impaired corporeal smooth muscle contractions elicited by electrical stimulation of adrenergic nerves and antagonized contractions induced by exogenous norepinephrine. We conclude that trazodone can enhance penile erection in man and propose a mechanism related to the alpha-adrenoceptor blocking properties of trazodone by interference with the sympathetic control of penile detumescence.

A case of priapism is described which complicated treatment of impotence with local injections of papaverine. A review is presented of the pertinent literature on the principles and complications of local pharmacotherapy of erection disturbances.

Intracavernous papaverine has found an important place in the management of male erectile failure. The effect of this mode of therapy was studied in 48 patients with psychogenic impotence. The average follow-up for this group of patients ranged from 7 months to 37 months (mean 16.3 months). All the patients in this group were advised sex therapy as an initial mode of therapy. On refusal to undergo sex therapy, they were offered an option of intracavernous papaverine injection. Papaverine appears to break the performance anxiety erectile failure cycle and was noted to have good results. Overall 57.9% patients expressed complete satisfaction with this mode of therapy. One patient (2.1%) developed priapism, which was adequately treated with intracavernous epinephrine. Use of low dosage of papaverine is suggested as an additional mode of therapy in the management of psychogenic impotence.

Prostaglandin E1 (PGE1) was used for diagnostic and therapeutic purposes in 149 men with erectile dysfunction over a period of 20 months (February 1987-October 1988). The intracavernous application of PGE1 in varying doses resulted in an erection sufficient for sexual intercourse in 79% of cases. In order to differentiate between vascular and non-vascular impotence, 5 micrograms PGE1 were found to be a sufficiently high and safe dose for the first intracavernous injection. Local discomfort, ranging from mild to severe pain after injection, was recorded in 40% of patients. A significant difference in severe side effects was found between arterial, venous and non-vasculogenic impotence, the highest incidence of local pain occurring in non-vasculogenic patients. The most striking result was the occurrence of 4 cases of priapism, all in the non-vascular group, 1 of these occurring after the injection of only 5 micrograms PGE1.

It has been suggested that vasoactive intestinal polypeptide (VIP) may be involved in the nervous control of penile tumescence and erection. VIP ergic nerves are present in the human penis, especially around the prudendal arteries and the corpus cavernosum. However, we have shown that VIP is unlikely to be non-adrenergic, non-cholinergic inhibitory transmitter for penile erection. The aim of this presentation is also to analyse other neurotransmitters of penile erection. This included discussion on: 1. motor neurotransmission; 2. non-adrenergic, non-cholinergic inhibitory transmission; 3. endogenously formed relaxants in the corpus cavernosum; 4. involvement of endothelium-derived relaxing factor(s) and; 5. role of prostanoids in penile erection and others.

A total of 78 patients 17 to 84 years old reported their experience via questionnaire with the papaverine-phentolamine injection technique for impotence. The mean number of injections used was 30.7. Penile induration occurred in 13 patients (16 per cent) and it was generally of limited extent. A higher incidence of induration was observed in those with vasculogenic impotence. Prolonged erection was reported by 23 per cent of the patients, 8 per cent of whom experienced erection for more than 12 hours. Priapism occurred exclusively in diabetic patients and patients with a neurological etiology of impotence. A total of 22 per cent of the patients reported moderate to severe pain with injection, 35 per cent indicated decreased quality of erection with time in response to the vasoactive agents and 28 per cent believed this therapy to be unsatisfactory. Among those who discontinued the injections 5 cited variability of erectile response (duration or quality) as the reason for discontinuation. A decrease in the effectiveness of the injections with time may be anticipated among some patients. For patients who face a penile implant without other options penile self-injection with vasoactive drugs is a reasonable alternative in that complications do not prevent successful prosthetic implantation.

Up to now 65 patients with erectile dysfunction were treated by means of corpus cavernosum-autoinjection-therapy (CAT). The only side effect observed were 6 prolonged erections, which could successfully be treated in 3 cases by puncture and aspiration of the corpora cavernosa. In another 3 cases prolonged erection subsided after an intracavernous injection of 2 mg metaraminol. Erection induced by CAT was immediately interrupted by metaraminol in 10 other patients.

Priapism is an alarming complication during treatment of erectile dysfunction with vasoactive drugs, particularly papaverine alone or in combination with phentolamine mesylate. An investigational protocol was designed to identify patients who are more susceptible to priapism after intracavernous injection of papaverine alone or with phentolamine. The protocol was applied in 331 men with impotence of various etiology. The association of a positive response to visual sexual stimulation and penile brachial index of more than 0.8 represented a higher risk for post-injection priapism. We were able to reduce the incidence of this compliance to 1% in the last 101 patients.

Intracavernous administration of papaverine and phentolamine has become an essential and indispensible element in the diagnosis and treatment of erectile dysfunction. This paper assesses the frequency and meaning of the main side effects of intracavernous injections (prolonged erections, fibrosis, etc.). It is concluded that the benefit from this new method definitely exceeds the possible risks. However, for the safe implementation of this method, close and intensive cooperation between the physician and his patient is a condition that has to be guaranteed. Each patient carrying out autoinjection therapy has to be examined at reasonable intervals to evaluate the to date unknown effects of long-term therapy.

Fibrotic penile lesions developed in 4 patients who had undergone intracorporeal injection of vasoactive agents. These lesions persisted for at least 3 months, and in some instances they caused pain and curvature of the penis during erection.

The obtention of an artificial erection with a single intracavernous injection (ICI) of vasoactive drugs, has upset our conceptions about erection and the approach for erectile failure. If this pharmacologic stimulation increases the reliability of some erection tests, their diagnosis value is still questioned. The complexity of both erection and vasomotricity pharmacology, make difficult the understanding of the mechanisms of these ICI. Their therapeutic value is reduced to the method by self injections, new treatment for impotence, even if it concerns only few impotent patients. Finally, the experimental feature and the unquestionable morbidity of these ICI, mainly priapism, impede their large diffusion. However, in spite of these doubts, this intracavernous pharmacology is a real progress for erection and its troubles.

Pharmacological erection is becoming an accepted form of treatment in the impotent patient. We report on our experience in 69 men with organic and psychogenic etiologies using intracorporeal injection with a mixture of papaverine hydrochloride and phentolamine mesylate. A good response was achieved in all patients except those with severe arterial or venous insufficiency. Although it was used primarily in cases of organic impotence, we found intracorporeal injection to be valuable in the patient with psychogenic impotence as an adjunct to sex therapy. Auto-injection was practiced by 74 per cent of our patients with a good response and 50 per cent noticed subjective improvement in the ability to obtain natural erections. Priapism was the most significant complication and occurred in 8.7 per cent of the patients. However, most patients have expressed satisfaction with this alternative to penile implantation.

The efficiency of intracavernous injection (ICI) of drugs for impotence is unfortunately counteracted by a real morbidity. The main danger lies in the persistence of this artificial erection. This pharmacologically induced prolonged erection (PIPE) appears like a real no-ischemic priapism. The risk of ischemic transformation must orientate the treatment of this frequent iatrogenic priapism. A decompressive puncture is often adequate. When ineffective, ICI of anti-erectogenic drugs will be indicated. But, this new treatment of priapism is not always effective, and most importantly, it can be dangerous, requiring considerable prudence for both indications and technics (risks of cavernous necrosis and of severe hypertensive crisis). The morbidity of this new pharmacological method is the major handicap to its wide use. Prevention now seems possible by carefully selection of indications for ICI and of the choice of both drugs and dosage, especially for high risk PIPE groups (neurologic and psychogenic impotence).

The recent finding of terbutaline as the treatment of choice to manage intraoperative penile tumescence with the patient under anesthesia (general and regional) has prompted us to use this beta-2 agonist (5 mg. orally) for persistent penile erection and priapism resulting from injection of pharmacological agents, such as phentolamine, phenoxybenzamine and papavarine, into the penis for erectile impotence. The drug also has been used successfully (0.25 to 0.5 mg. intravenously or subcutaneously) to treat priapism developing despite a cavernosum-spongiosum shunt procedure. This and other pure beta 2 agonists will have an important role in the treatment of undesirable and painful penile erection, alone or in association with other invasive and noninvasive intervention.