Avances en anestesia local y su utilidad en el ámbito de la odontología militar: mesilato de fentolamina / New advances in local anesthetics and their applications in military dentistry: phentolamine Mesylate

Objetivo: Describir el mecanismo de acción del mesilato de fentolamina (MF), que es un producto poco conocido en España, capaz de revertir el efecto de los anestésicos locales empleados en odontología, enumerar sus indicaciones y analizar su efectividad y seguridad. Fuentes de datos: se ha realizado una revisión bibliográfica en las principales bases de datos médicas así como en buscadores genéricos. Selección de estudios: Se ha seleccionado los estudios clínicos, llevados a cabo desde su aprobación como medicamento de uso en el campo odontológico, que han sido realizados en los países donde se comercializa con la misma formulación que en España. Recopilación de datos: Se han obtenido datos sobre el tiempo medio de reducción del efecto anestésico y sobre la incidencia de efectos adversos. Síntesis de datos: Todos los estudios muestran una eficacia y presencia de reacciones adversas similares, en relación con la administración del MF y de un placebo, independientemente de la forma en que se ha llevado el estudio. Discusión: El uso del MF en la actuación clínica diaria, debe ser una decisión del profesional basada en la evidencia científica y en el coste-beneficio de su administración, debiendo seleccionar que pacientes son susceptibles de su administración. Conclusiones: El MF es un medicamento eficaz y seguro en la reducción del efecto anestésico y con indicaciones tanto en el ámbito de la odontología civil como militar

Objective: Describing the mechanism of action of the Phentolamine Mesylate (PM), which is not a so well known product in Spain, capable of reversing the effect of local anesthetics used in dentistry, highlighting its indications and analizing its effectiveness and safety. Data sources: A literature review has been carried out in the main medical databases as well as in generic search engines. Selection of studies: Clinical studies have been selected, carried out since its approval as a medicine for use in the dental field, which have been tested in the countries where it is marketed with the same formula as in Spain. Data collection: Data was obtained on the average time of reduction of the anesthetic effect and on the incidence of adverse reactions. Data synthesis: All studies show an efficacy and presence of similar adverse reactions, related to the administration of PM and of a placebo, regardless of the way in which the study was conducted. Discussion: The use of the PM in the daily practice, should be a decision that must be taken by the professional based on the scientific evidence and the cost-benefit of its administration, having to select which patients are susceptible to its administration. Conclusions: PM is an effective and safe medicine in the reduction of the anesthetic effect and with indications both in the field of civil and as in military dentistry

Avaliação do potencial antirreabsortivo de géis de fentolamina e propranolol em reimplantes dentários / Evaluation of the anti-resorptive potential of phentolamine and propranolol gels on tooth replantation

Este trabalho teve como objetivo avaliar os efeitos da aplicação tópica de fármacos bloqueadores adrenérgicos (AR) sobre o processo de reparo periodontal de dentes reimplantados em ratos. Inicialmente, cultura de fibroblastos do ligamento periodontal humano foi utilizada para avaliar qualitativamente a citotoxicidade de soluções etanólicas de fentolamina (bloqueador α-AR) e propranolol (bloqueador ßAR) em diferentes doses (0,75 µg/mL, 2,5 µg/mL, 10 µg/mL e 100 µg/mL), após 24 horas de exposição. Posteriormente, modelo animal de avulsão e reimplante dentário foi utilizado para avaliar o potencial antirreabsortivo do bloqueio adrenérgico local com géis de fentolamina (F) ou propranolol (P), em excipiente de carboximetilcelulose (CMC). Incisivos superiores direitos foram extraídos de 48 ratos Wistar machos, armazenados em guardanapo de papel por 30 minutos, e distribuídos aleatoriamente em oito grupos (n=6) de acordo com a medicação intracanal: F0.75, F10 e F100 receberam gel de fentolamina nas concentrações 0,75 µg/mL, 10 µg/mL e 100 µg/mL, respectivamente; P2.5, P10 e P100 receberam gel de propranolol nas concentrações 2,5 µg/mL, 10 µg/mL e 100 µg/mL, respectivamente; HC e CMC receberam pasta de hidróxido de cálcio e gel de carboximetilcelulose, respectivamente. Os animais foram eutanasiados 30 dias após o reimplante e as seguintes análises foram realizadas: microtomografia (volume, superfície, proporção e densidade de tecido mineralizado), histomorfometria (áreas de reabsorção radicular inflamatória, reabsorção por substituição, anquilose e reparo periodontal) e histoquímica (atividade osteoclástica). Os dados foram analisados estatisticamente por meio de ANOVA e teste de Tukey ou Kruskal Wallis e teste de Dunn, de acordo com sua normalidade (α=5%). A análise qualitativa da viabilidade celular demonstrou que a dose de 100 µg/mL dos fármacos apresentou alta citotoxicidade, com 100% das células inviáveis, e as demais doses propiciaram viabilidade celular semelhante. As análises microtomográfica e histomorfométrica das amostras in vivo não revelaram qualquer diferença estatística significante entre os fármacos testados e suas diferentes doses (p>0,05). No entanto, P10 e F10 apresentaram qualitativamente um melhor resultado, pois foram os únicos grupos classificados com áreas de intenso reparo periodontal (P10) e de discreta reabsorção radicular inflamatória (F10 e P10). O tratamento com F10 e P10 diminuiu significativamente o número de osteoclastos em comparação com as outras medicações tópicas (p<0,05). Concluiu-se que a aplicação tópica de géis de fentolamina e propranolol na dose de 10 µg/mL diminuiu significativamente a atividade osteoclástica sem causar efeitos citotóxicos.(AU)

This study aimed to evaluate the effects of topical application of adrenergic (AR) blocking drugs on the periodontal repair process of replanted teeth in rats. First, culture of human periodontal ligament fibroblasts was used to qualitatively assess the cytotoxicity of ethanolic solutions of phentolamine (α-AR blocker) and propranolol (ßAR blocker) at different doses (0.75 µg/mL, 2.5 µg/mL, 10 µg/mL and 100 µg/mL) after 24 hours of exposure. Then, animal model of tooth avulsion and replantation was used to evaluate the anti-resorptive potential of local adrenergic blockade with phentolamine (Ph) or propranolol (Pr) gels, in carboxymethylcellulose excipient (CMC). Maxillary right incisors were extracted from 48 male Wistar rats, stored in paper napkins for 30 minutes, and randomly distributed into eight groups (n = 6) according to intracanal medication: Ph0.75, Ph10 and Ph100 received phentolamine gel at concentrations of 0.75 µg/mL, 10 µg/mL and 100 µg/mL, respectively; Pr2.5, Pr10 and Pr100 received propranolol gel at concentrations of 2.5 µg/mL, 10 µg/mL and 100 µg/mL, respectively; CH and CMC received calcium hydroxide paste and carboxymethylcellulose gel, respectively. The animals were euthanized 30 days after replantation and the following analyzes were performed: microtomography (volume, surface, proportion and density of mineralized tissue), histomorphometry (areas of inflammatory root resorption, replacement root resorption, ankylosis and periodontal repair) and histochemistry (osteoclastic activity). Data were analyzed statistically by means of ANOVA and Tukey's test or Kruskal Wallis and Dunn's test, according to their normality (α = 5%). The qualitative analysis of cell viability demonstrated that the dose of 100 µg/mL of the drugs presented high cytotoxicity, with 100% of the cells non-viable, and the other doses provided similar cell viability. Microtomographic and histomorphometric analyzes of in vivo samples did not reveal any significant statistical difference between the tested drugs and their different doses (p>0.05). However, Pr10 and Ph10 presented qualitatively a better result, as they were the only groups classified with areas of intense periodontal repair (Pr10) and discrete inflammatory root resorption (Ph10 and Pr10). Treatment with Ph10 and Pr10 significantly decreased the number of osteoclasts compared to the other topical medications (p<0.05). It was concluded that topical application of phentolamine and propranolol gels at a dose of 10 µg/mL significantly decreased osteoclastic activity without causing cytotoxic effects(AU)

Phase Four, Randomized, Double-Blinded, Controlled Trial of Phentolamine Mesylate in Two- to Five-year-old Dental Patients.

PURPOSE: The purpose of this study was to evaluate, using a randomized, double-blind methodology: (1) the safety of phentolamine mesylate (Oraverse) in accelerating the recovery of soft tissue anesthesia following the injection of two percent lidocaine plus 1:100,000 epinephrine in two- to five-year-olds; and (2) efficacy in four- to five-year-olds only. METHODS: One hundred fifty pediatric dental patients underwent routine dental restorative procedures with two percent lidocaine plus 1:100,000 epinephrine with doses based on body weight. Phentolamine mesylate or a sham injection (two to one ratio) was then administered. Subjects were monitored for safety and, in four- to five-year-olds, for efficacy during the two-hour evaluation period. RESULTS: There were no significant differences in adverse events between the phentolamine and sham injections. Compared to sham, phentolamine was not associated with nerve injury, increased analgesic use, or abnormalities of the oral cavity. Phentolamine was associated with transient decreased blood pressure in some children. In four- and five-year-olds, phentolamine induced more rapid recovery of lip anesthesia by 48 minutes (P<0.0001). CONCLUSIONS: Phentolamine was well tolerated and safe in three- to five-year-olds; in four- to five-year-olds, a statistically significant more rapid recovery of lip sensation compared to sham injections was determined.

Sequential drug verification errors resulting in wrong drug administration during caesarean section.

An intravenous bolus of phentolamine was inadvertently given to a parturient during an emergency caesarean section following delivery of her infant when the intention had been to give an intravenous bolus of 5 IU Syntocinon. Root cause analysis identified a series of errors originating in the hospital pharmacy when one drug package was mistakenly issued in place of another. Subsequent checks failed to detect the original mistake. The final and most important check immediately before intravenous administration was also at fault. This case highlights a systems failure that permitted issue, transportation and administration of the wrong drug to a parturient. Robust measures to ensure avoidance of drug administration errors should be evaluated and introduced where possible.

Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction.

Erectile dysfunction (ED) is becoming an increasingly common problem and although oral therapies offer first-line treatment for many men, they are contraindicated or ineffective in substantial groups of patients. Intracavernosal injection (ICI) therapy is the most effective nonsurgical treatment for ED and offers an effective alternative to oral therapy. Sufficient arterial blood supply and a functional veno-occlusive mechanism are prerequisites in the attainment and maintenance of a functional erection. Invicorp (Plethora Solutions, London, UK) is a combination of vasoactive intestinal polypeptide (VIP) 25 microg and phentolamine mesylate 1 or 2 mg for ICI in the management of moderate to severe ED. The two active components have complementary modes of action; VIP has a potent effect on the veno-occlusive mechanism, but little effect on arterial inflow, whereas phentolamine increases arterial blood flow with no effect on the veno-occlusive mechanism. Clinical studies showed that Invicorp is effective in >or=80% of men with ED, including those who have failed to respond to other therapies and, unlike existing intracavernosal therapies, is associated with a very low incidence of penile pain and virtually negligible risk of priapism. We estimate that there are >5.9 million men in the USA alone for whom oral ED drugs are not a viable treatment option, and for whom Invicorp might offer a safe and effective alternative.

Injection therapy for the treatment of erectile dysfunction: a comparison between alprostadil and a combination of vasoactive intestinal polypeptide and phentolamine mesilate.

OBJECTIVE: To compare two injectable treatments, alprostadil 5-20 microg powder for injection and a combination of vasoactive intestinal polypeptide (VIP) and phentolamine in patients with erectile dysfunction (ED). DESIGN AND METHODS: This was an open multicentre, randomised crossover study comprising two phases. The first phase established the dose of each drug required to produce an erection suitable for sexual intercourse (grade 3 erection). In phase 2, responders to both drugs received, in random order, four doses of VIP/phentolamine, presented as ampoules, and four doses of alprostadil, presented as powder for injection. This was followed by four doses of VIP/phentolamine, presented in an autoinjector. In both phases, patient preference was assessed for each preparation. RESULTS: 187 patients were recruited. In the first phase, both treatments were effective, (83% alprostadil vs. 73% VIP/phentolamine, p = 0.002) but more patients preferred VIP/phentolamine (69 vs. 31%, p = 0.011). In phase 2 (n = 107), the proportion of injections that produced a grade 3 erection was similar for all three treatments (83-85%), but both presentations of VIP/phentolamine (ampoule and auto-injector) were preferred by significantly more patients (p < 0.001). Compared with both presentations of VIP/phentolamine, alprostadil produced a higher frequency of pain (28% of injections vs. 3% for each VIP/phentolamine presentation; p < 0.001) and a lower frequency of facial flushing (3 vs. 16-17%; p < 0.001). CONCLUSIONS: VIP/phentolamine and alprostadil were effective treatments for ED, however the VIP/phentolamine combination was preferred by more patients, which may be because it was much less likely to cause pain.

[Postponed or canceled drug challenge tests and side effects of the test drug--a report of four cases].

Drug challenge test (DCT) is performed to evaluate chronic pain pharmacologically and determine its medical treatment. One test drug is administered in one day for DCT and characterization of the test drug. Four patients developed side effects of the test drugs for DCT in whom other drug tests were postponed or canceled. A 58-year-old man with multiple arthritis of rheumatic arthritis and fibromyalgia had headache, nausea, and vomiting all day after ketamine test. A 76-year-old man with chronic general pain and failed back surgery syndrome had vomiting and abdominal discomfort two hours after morphine test and had redness and itching on his bilateral forearms the following day. A 78-year-old man with chronic lumbar and right lower limb pain due to L 4-5 lumbar disc herniation and postherpetic neuralgia felt dizzy, fell down and bruised on his lower back and left knee twelve hours after morphine test. A 32-year-old woman with chronic pelvic pain had skin eruption on her thigh the day after phentolamine test. Although the amount of the test drug in DCT is small and its half-life is short, long-term side effects might occur. We should decrease the amounts or frequencies of ketamine and morphine, and administer them taking long intervals before other tests.

A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient?

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.

A prospective randomized study to optimize the dosage of trimix ingredients and compare its efficacy and safety with prostaglandin E1.

Intracavernous injection of Trimix (Tx) is indicated for patients unsuitable for prostaglandin E1 (PgE1) injection due to lack of response, pain or cost. We believe that the ideal ratio of ingredient doses in Tx is yet to be found. We postulated that increasing the doses of individual drug components in an orderly manner would convey important data on penile hemodynamic response. Such information is needed to choose an effective and less costly alternative to PgE1 with least side effects. We set out to evaluate the impact of varying the ingredient dosage on response and short-term safety of Tx compared with PgE1. We prospectively randomized 180 consecutive patients with erectile dysfunction into nine equal groups and each group received a different dose of Tx, namely phentolamine (1 mg) plus one dose of PgE1 (2.5, 5 or 10 microg) and one dose of papaverine (5, 10 or 20 mg). Each patient was injected with 20 microg PgE1 and one dose of Tx in two clinic visits 1 week apart. Following injection, duplex ultrasound of cavernous arteries and axial rigidometry were carried out. Patients ranked the quality of erection, estimated overall satisfaction and reported time to detumescence and side effects. Patients' mean age was 50.5+/-11.7 y with underlying organic condition in 91.1%. There were no significant differences between PgE1 and Tx with regard to peak cavernous artery flow, time to erection, patients' satisfaction, average axial rigidity and pain. PgE1 produced higher end diastolic velocity, shorter duration of erection and less priapism. Patients did not show a preference for either drug or any particular dosage. We conclude that even at the smallest dose of ingredients of Tx, there are no significant differences in hemodynamic effects, rigidity, pain and self-satisfaction between the two drugs. However, Tx produces a longer duration of erection and more priapism than PgE1.

[An experimental study on the role of protein kinase C in the down-regulation of fibroblast proliferation in normal skin and hyperplastic scar by adrenaline].

OBJECTIVE: To investigate the role of protein kinase C (PKC) in the down-regulation of fibroblast proliferation in normal skin (NFb) and hyperplastic scar (SFb) by adrenaline. METHODS: Human NFb and SFb cells were cultured in vitro. Phentolamine (in final concentrations of 0 and 3 x 10(-6) micromol/L) was added to the culture medium. One hour later, adrenaline in different final concentrations (0.00, 0.05, 0.10, 0.20 micromol/L) was added to the culture medium and incubated for 24 hours. The cellular proliferation activity and cell viability rate were determined with MTT. The cell culture supernatant was harvested for the determination of LDH activity to assess the toxicity of phentolamine and adrenaline. The phosph-PKC activity was determined with Western-blotting and was semiquantitatively analyzed. RESULTS: (1) After stimulation with adrenaline alone, or combined 0.20 micromol/L adrenaline with 3 x 10(-6) micromol/L phentolamine, the cell viability of both NFb and SFb decreased significantly (P < 0.05 or 0.01). (2) There was no difference in the LDH activity between the cells either stimulated by adrenaline in all concentrations or by combination of adrenaline and phentolamine (P > 0.05). (3) The phosphorylation of PKC in NFb and SFb cells stimulated by 0.05, 0.10, 0.20 micromol/L adrenaline was obviously higher than that before stimulation (P < 0.01). When phentolamine in the concentration of 3 x 10(-6) micromol/L was used alone for stimulation, the phosphorylation of PKC in NFb cells (123 +/- 5) was also evidently higher than that before stimulation (80 +/- 5, P < 0.01). But there was no such effect on SFb cells (P > 0.05). When adrenaline in the concentration of 0.05, 0.10 or 0.20 micromol/L was separately added together with phentolamine in the dose of 3 x 10(6) micromol/L for the stimulation, the phosphorylation of PKC in NFb and SFb cells was evidently lower than that when 3 different concentrations of adrenaline was used alone for stimulation (P < 0.01). CONCLUSION: Adrenaline can inhibit the proliferation of NFb and SFb by activating PKC through binding alpha adrenaline receptor.

Intracavernous sodium nitroprusside (SNP) versus papaverine/phentolamine in erectile dysfunction: a comparative study of short-term efficacy and side-effects.

OBJECTIVE: The aim of our work is to evaluate the efficacy of intracavernous sodium nitroprusside (SNP) in management of erectile dysfunction (ED) in a clinical comparative study with papaverine/phentolamine in ED patients. METHODS: The study included 40 patients with ED divided into two groups. Group I include 20 patients receiving intracavernous (30 mg papaverine + 1 mg phentolamine) followed 1 week later by intracavernous 300 microg SNP. Group II included 20 patients receiving the same regimen of group I but with intracavernous SNP first followed by papaverine/phentolamine 1 week later. All patients were assessed clinically for their response and any developing complications. RESULTS: The numbers of good and poor responders were not statistically significant (P > 0.05) among the two groups. The mean erectile duration of SNP was similar to bimix (P > 0.05). No side-effects whether local or systemic occurred with SNP while priapism and local penile pain were recorded with bimix solution. CONCLUSIONS: Intracavernous pharmacotherapy is still a reliable method both for diagnosis and for treatment of ED. While preliminary results of our study show a potential of SNP to be an effective and safe intracavernous agent, long-term self-injection clinical trials are needed before large-scale usage is recommended.

[Lessons learned from anesthetic management of pheochromocytoma resection: a report of three cases].

The anesthetic management of patients with pheochromocytoma, in which drastic hemodynamic changes may occur, is still a challenge to even the most experienced anesthesiologist, although the perioperative mortality has been reduced remarkably. We report three patients who developed unexpected major complications during elective resection of a pheochromocytoma. The Case 1 patient was a 46 year-old woman who developed ventricular tachycardia immediately after administration of ephedrine for transient hypotension induced by excessive phentolamine. Even a mild beta adrenergic agent may cause extraordinary stimulation to myocardium under alpha blockade. The Case 2 patient was a 44 year-old man who needed intensive vasodilating therapy due to an exaggerated cardiovascular response to intraoperative surgical stress. He developed severe metabolic acidosis resembling hyperdynamic shock before resection of the tumor, although blood pressure was controlled within the expected range. The Case 3 patient was a 60 year-old woman who did not receive preoperative alpha blocker therapy because she lacked cardiovascular symptoms. However, she revealed a high level of systemic vascular resistance after induction of general anesthesia and needed moderate inotropic support to compensate for an abrupt reduction of vascular resistance after resection of the tumor. The pathophysiology of the disease is complex and anesthetic care must be tailored in accordance with each patient's situation.

The incidence and management of priapism in Western Australia: a 16 year audit.

The objective of the study was to conduct a retrospective audit of patients who presented with priapism in Western Australia during the years 1985-2000. We searched the records of the teaching hospitals in metropolitan Perth and those of the Keogh Institute for Medical Research for the diagnostic code for priapism. A total of 82 episodes of priapism in 63 patients occurred over this 16 year period. In all, 62 episodes occurred after intracavernosal injections (ICI) and 20 were due to other causes. Treatment of priapism included simple aspiration of blood, intracavernosal injection of alpha-adrenergic agents and surgical shunt procedures. Priapism occurring outside the setting of ICI was more likely to require surgery; seven of 20 episodes. After ICI therapy, eight of 62 episodes required shunts. The use of prostaglandin E1 as the drug of choice in ICI therapy in 1989 led to a fall in the incidence of ICI-induced priapism. Priapism is a major side effect of ICI therapy and an uncommon, although important, side effect of other conditions. The incidence of priapism has fallen with the introduction of prostaglandin E1 monotherapy as the favoured drug for ICI therapy of erectile failure.

Role of sympathetic innervation in the defecation mechanism: a novel concept of its function.

BACKGROUND/OBJECTIVE: Because the role of sympathetic innervation in the defecation mechanism is still vague and unidentified, this study was performed to investigate this issue. METHODS: The effect of individual administration of alpha- and beta-adrenoceptor blocking agents (3 mg/kg phentolamine mesylate and 1 mg/kg propranolol hydrochloride, respectively) and the effect of thoracolumbar sympathectomy on anal and rectal pressures was studied in 13 mongrel dogs. Pressures were measured by a 2-channel microtip catheter. Bilateral thoracolumbar sympathectomy was performed by excising the sympathetic ganglia from T11 to L2. Incremental rectal filling using a rectal balloon with simultaneous anal and rectal pressure measurements was continued until balloon expulsion was achieved. RESULTS: Rectal balloon distension with 30 to 40 mL of saline affected rectal pressure increase (P < 0.001 ), anal pressure decrease (P < 0.01), and balloon expulsion. Following administration of either phentolamine or propranolol or after thoracolumbar sympathectomy, rectal pressure declined (P < 0.05), but anal pressure showed no change (P > 0.05). At a rectal balloon volume of 50 to 60 mL of saline, rectal pressure increased (P < 0.001), anal pressure decreased (P < 0.01), and the balloon was expelled. CONCLUSION: Sympathetic rectal innervation may have a role during both the filling and evacuation phases of the defecation mechanism. During rectal filling, it most likely maintains rectal compliance. During evacuation in cases of rectal sympathetic block or denervation, a larger volume than usual of rectal distension is needed to induce rectal contraction and evacuation.

Methylene blue as a means of treatment for priapism caused by intracavernous injection to combat erectile dysfunction.

OBJECTIVE: The authors observed priapism as a side effect occuring during the intracavernous treatment of erectile dysfunction. Earlier priapism had been treated with an intracavernous injection of sympatomimetics; unfortunately several complications and contraindications were found. PATIENTS AND METHODS: Methylene blue was applied in the treatment of five patients. First a corpus cavernosum punction was performed and some blood was aspirated from the penis. Finally 100 mg of Methylthionin Chlorati was injected into the corpus cavernosum. RESULTS: A sufficient detumescence was observed in all of these cases. There were no complications. The method was applied effectively in two cases after an unsuccessful punction. CONCLUSION: The autors recommend intravenous methylene blue for the treatment of priapism. According to their experience this method is free of complications and as effective as a sympathomimetics treatment. As they think, it can be recommended in any manifestations of priapism because its force of action appears to be both chemically and biologically clear.

Phentolamine administration increases blood S100B protein levels in pediatric open-heart surgery patients.

AIM: Phentolamine administration during open-heart surgery shortens the cooling and rewarming phases of cardiopulmonary bypass (CPB) and hastens weaning from mechanical ventilation and extubation. Data on the effects of phentolamine on cerebral circulation and function in this setting are lacking. This study reports the cerebral effects of phentolamine using blood S100B protein levels and the middle cerebral artery pulsatility index (MCA PI). METHODS: Sixty pediatric patients undergoing congenital heart disease repair were randomly assigned to receive either phentolamine 0.2 mg kg(-1) i.v. (n = 30) or placebo (n = 30) before the cooling and rewarming phases of CPB. Samples for S100B measurement were collected at seven predetermined time-points before, during and after surgery. MCA PI values were recorded at the same times as sampling. RESULTS: S100B blood levels were higher in the phentolamine-treated group than in controls after rewarming (3.53 +/- 1.88 vs 1.58 +/- 0.53 microg l(-1); p < 0.001), remained persistently higher at the end of surgery (2.95 +/- 0.91 vs 0.79 +/- 0.21 microg l(-1); p < 0.001) and returned to normal ranges 12 h later than in the placebo group (p > 0.05). MCA PI values were also significantly higher at the end of surgery in the phentolamine-treated group (1.83 +/- 0.50 vs 1.22 +/- 0.34; p < 0.01). Cooling and rewarming times were shorter in the phentolamine-treated group (p < 0.01, for all). CONCLUSION: Despite improved peripheral vasodilatation and perfusion, phentolamine administration in pediatric open-heart surgery is correlated with increased cerebrovascular resistance and brain damage.

Erectile dysfunction: oral pharmacotherapy options.

Erectile dysfunction (ED) (impotence) is a widespread, age-related problem, which affects 52% of men between 40 and 70 years of age. It is classified as psychogenic, organic, or mixed psychogenic and organic. ED is not a problem only of men, because the relationship between partners can also be disturbed. Therefore, adequate treatment of ED is needed and the most convenient and simplest way is oral drug therapy. Sildenafil, phosphodiesterase-(PDE)-5-selective inhibitor has been the drug of choice for patients with ED since it has been launched in March 1998. The results of various studies have confirmed the efficacy of the drug in men with ED of various etiologies, as well as the positive effect of sildenafil on the quality of a partnership. The most frequent adverse effects documented with sildenafil usage are headache, flushes, dyspepsia, visual disturbances and nasal congestion/rhinitis. These adverse effects are dose-related, usually transient and mild, with low withdrawal rate. Several studies performed recently have shown that sildenafil is a safe and effective treatment of ED in patients with cardiovascular disease, who do not take nitrates or nitrate donors concomitantly. Other oral medications for ED include apomorphine, phentolamine, yohimbine, trazodone, testosterone and new PDE-5 inhibitors in Phase III clinical trials, such as vardenafil and tadalafil. It is obvious, according to recent data, that the concept of PDE-5 inhibition has a central position in oral pharmacotherapy of ED. However, larger clinical studies of efficacy and safety should be carried out using most of the other above-mentioned oral agents and these may also gain a place in the therapy of ED. There are no studies directly comparing sildenafil and other treatments of ED or assessing its role in combination with other therapies. According to the present knowledge, the quality of life, not only of patients but also of their sexual partners, will be improved significantly with sildenafil usage and this is an important precondition for overall health ofboth. Sildenafil is thus a highly effective peroral treatment for ED in patients without contraindications for its use, which can be considered as the firstline therapy with an acceptable risk-benefit ratio.