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PubMed1994

[Diagnosis and treatment of impotence. Indications of intracavernous injections].

Based on progress in our understanding of the physiology of erection, intracavernous injections of vasoactive substances have completely changed the treatment of impotence. Essentially, erection results from the effect of smooth muscle relaxation in the vascular walls leading to local fall in vascular resistance and increased arterial flow combined with smooth muscle relaxation within the sinusoid spaces of the cavernous bodies. Smooth muscle cell tone is regulated not only by the classical norepinephrine and acetylcholine neurotransmitters, but also by other non-adrenergic and non-cholinergic neurotransmitters released locally. Although the "erectile neurotransmitter" has not been identified parasympathetic nerve terminaisons release nitric oxide (NO) a powerful myorelaxant agent. NO is also synthetized by the endothelial cells on the internal surface of the sinusoidal spaces. These recent findings have led to the use of papaverin to reduce the level of intracellular calcium, alpha-blockers to antagonize alpha-receptor and prostaglandin to inhibit norepinephrine release. Vasoactive intestinal polypeptide, a myorelaxing agent, and linsidomine which favours NO release have also been used. Diagnostic tests by intracavernous injections are indicated as part of the complete work-up in patients consulting for impotence. Therapeutic indications for auto-injections require careful choice of the agent and the dosage to inject depending on the cause of the impotence and the patient's demands and capacity to learn the technique. Papaverin or prostaglandin E1 alone or in combination with phentolamine give good results. Rigid erections can be obtained in over 60% of the patients. Alpha-blockers appear to be the least active in terms of rigidity. Mid-term results of intracavernous fibroses have been reported after papaverine injections. Priapism is the main secondary effect of intracavernous injections.

Humans↗
PubMedDate not supplied

[Evaluation of clinical usefulness of direct drug injections for increasing local circulation, into cavernous bodies of the penis for treatment of erection impotence in patients with diabetes mellitus].

The study aimed at comparing an effectiveness of drugs increasing local blood flow injected into cavernous bodies of penis in the treatment of erective impotence in diabetic patients. Fifteen diabetic patients aged between 33 and 60 years with impotence lasting for 4 years have been selected. Patients have been treated with papaverine HCl in the dose of 20-40 mg, papaverine HCl in the same dose combined with phentolamine 5 mg, and prostaglandin E1 in the dose of 20 micrograms. Each patient has been all tested drugs. The most favourable results, i.e. most effective and without adverse reactions (priapism), have been produced by prostaglandin E1 which seems a drug of choice in the treatment of erective impotence in patients with long-lasting diabetes mellitus.

Adult↗
PubMed1994

The change of penile blood thromboxane B2 and prostacyclin after intracavernous injection of vasoactive drugs for the treatment of arteriogenic impotence.

Penile hypercoagulability during erection may predispose to aging vascular changes and, eventually, arteriogenic impotence. The relationship of penile blood thromboxane B2 and 6-keto-prostaglandin F1 alpha in both psychogenically and arteriogenically impotent patients after intracavernosal treatment with papaverine plus phentolamine or prostaglandin E1 was evaluated. No significant change in penile blood thromboxane B2 was observed with treatment of these vasoactive drugs. On the other hand, penile blood 6-keto-prostaglandin F1 alpha was significantly increased with the injection of 30 mg of papaverine plus 0.5 mg of phentolamine, and of 20 micrograms prostaglandin E1. Furthermore, the prostacyclin-to-thromboxane A2 ratio for the patient who received papaverine plus phentolamine was significantly lower than that for the same individual receiving prostaglandin E1. Our preliminary findings suggest that penile blood prostacyclin may participate in the pathogenesis of arteriogenic impotence and priapism.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Transfusion therapy in sickle cell disease patients: methods and acute indications.

Management of transfusion therapy in sickle cell disease patients with acute complications is often made difficult because of confusing indications, a variety of methods, disparate goals, and varying needs for maintenance transfusion. In priapism, acute chest syndrome, many major surgical procedures, toxemia of pregnancy, and cerebrovascular accidents, the target hemoglobin A level should be made as close to 100% as possible by mechanized red blood cell exchange. If mechanized exchange is unavailable, manual exchange should be instituted. Hemoglobin A should be maintained at greater than 60% to 70% by periodic simple transfusion until patients are fully recovered. Stroke patients should undergo maintenance transfusions for at least 3 years and perhaps 5 to 12 years. Physicians and patients should be aware of the transfusion-related risks of hepatitis and HIV infection. Alloimmunization and iron overload should be minimized in patients requiring frequent transfusions and chelation therapy should be utilized for iron overload.

Anemia, Sickle Cell↗
PubMed1994

Common problems in sickle cell disease.

Sickle cell disease is transmitted as an autosomal recessive trait. Symptoms of pallor, fever, abdominal and joint pain, and swelling of the liver, spleen, hands and feet first appear near the latter part of the first year of life. Intravascular sickling affects all organs. For clinical and therapeutic purposes, exacerbations may be classified as vasoocclusive or pain, aplastic, hemolytic or sequestration crisis. In addition to infection, complications include severe pain, cerebrovascular accidents, cholelithiasis, bone infarction, heart failure, hypotension and priapism. The most common cause of early childhood death is septicemia or meningitis due to Streptococcus pneumoniae. Complications may be reduced or prevented by early diagnosis through newborn screening, patient education, routine immunizations, administration of folic acid, pneumococcal and influenza vaccinations, penicillin prophylaxis, and early diagnosis and aggressive treatment of complications.

Anemia, Sickle Cell↗
PubMed1994

[Intracavernous auto-injection of prostaglandin E1 for diagnosis and treatment of erectile dysfunction].

34 impotent patients were offered auto-injection therapy and all except 2 began treatment. Prostaglandin E1 (PGE) was used regularly for a mean of 8.6 months (range 1-17). The onset of erection was 5-30 min (mean 11.4) after injection and it lasted at least 30 min (mean 106.2 min). An erection of more than 6 hrs was observed in only 2 patients. There have been no instances of cavernous fibrosis, chemical priapism or systemic reactions. The most common adverse effect was penile pain after injection. It was mild to moderate in 4 patients (11.7%), and in only 1 was it severe enough to require stopping treatment. Overall, intracavernous injection of PGE appears to be safe, effective treatment for impotence without side-effects other than pain after injection in a few.

Adult↗
PubMed1993

[Complications of intracavernous pharmacologic infusion in impotence. Long-term results].

The large scale employment in recent years of vasoactive drugs in the treatment of impotence forms the basis for a significant statistical study on incidence of complications and collateral effects. We studied 658 patients submitted to ICF (intracavernous pharmacoinfusion) diagnostic and therapeutic in the last 6 years (1986-1992). The patients have been shared groups according to the period and the treatment: in 226 cases we have utilized papaverine, in 224 cases phentolamine-papaverine association and in 208 cases prostaglandin E1. In the last group the complications have been lower: echymosis and haematoma 0.5%, priapism 1.5%, intracavernous fibrosis 1%, fibrotic knots 0.5%. In conclusion we confirm the validity of treatment with PGE1 intracavernous infusion.

Adult↗
PubMed1993

[Metastatic disease of the penis. Report of 3 cases].

Metastatic lesions of the penis are uncommon, only some 200 cases having been reported in the literature. Priapism is the most frequent symptom, although increased penis size, ulceration and nodes formation have also been described; metastasis happens simultaneously in 20% cases while in 50% of cases they appear 2 years after initial diagnosis. Survival of untreated patients has not exceed 24 weeks, whereas treated patients have survived 47 weeks.

Aged↗
PubMed1993

[Duplex ultrasound of the penis. Value of a new diagnostic procedure based on over 1,000 patients].

In the period between December 1989 and December 1991, penile duplex sonography was performed, mostly after intracavernous injection of prostaglandin E1 in more than 1000 patients with erectile dysfunction or other penile disorders (Peyronie's disease, penile deviations, priapism). The most reliable evaluation criterion was the assessment of the peak flow velocity. Values of more than 25-30 cm/s with reference to the deep penile artery and more than 35-40 cm/s with reference to the dorsal artery indicated the integrity of the penile arteries. The assessment of the resistancy index has not proved to be a useful criterion because of its dependence on diastolic blood flow and therefore on the erection state, especially in cases of so-called cavernous insufficiency. Similar observations were made concerning the assessment of the increase in diameter of the deep penile arteries after intracavernous application of vasoactive drugs. Based on the fact that the increase in diameter is more dependent on the relaxation capacity of the cavernous smooth musculature and not on the actual blood flow, the measured values may be equal both in normal and in clearly disturbed blood circulation. In conclusion, duplex sonography is at present, together with color Doppler imaging, the most reliable vascular diagnostic tool and has clearly proved its superiority both to conventional penile Doppler imaging and penile angiography.

Blood Flow Velocity↗
PubMed1995

[Effectiveness of and tolerance to intracavernous injection of moxisylyte in patients with erectile dysfunction: effect/dose relationship versus placebo].

The authors investigated the optima dose (efficacy and safety) of moxisylyte, an alpha-blocking agent, in a double-blind placebo-controlled crossover study in 30 patients. The origin of the erectile dysfunction was predominantly psychological in 14 patients and neurological in 16 patients. Each patient received 4 intracavernous injections in a randomized order (placebo, 10, 20, 30 mg of moxisylyte) at 7-day intervals. Regardless of the dose, moxisylyte induced significantly greater penile responses than placebo on all erection criteria. The frequency of responses allowing sexual intercourse appeared to be dose-dependent in the two aetiological groups. The erectile responses most frequently obtained were complete rigidity in the "neurological" group and tumescence in the "psychological" group. The safety was excellent for 95.6% of injections and no case of priapism was observed. One patient (neurological patient) experienced two prolonged erections after the dose of 20 mg and another patient (psychological patient) reported 2 headaches after the dose of 30 mg. No pain was experienced on injection. Moxisylyte is very well tolerated and is able to induce an erectile response from the dose of 10 mg. This dose appears to be sufficient in patients with central neurological erectile dysfunction; a dose of 20 mg tends to improve the quality of response in patients with a predominantly psychological disorder, although the differences observed between the doses were not statistically significant in this number limited of patients.

Adult↗
PubMed1996

The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience.

PURPOSE: Prostaglandin E1 (PGE1, alprostadil) is used worldwide for self-injection therapy in erectile failure and was recently officially approved for this purpose in the United States and most European countries. Therefore a comprehensive overview on biochemistry, pharmacology and therapeutic results of PGE1 is provided. MATERIALS AND METHODS: The relevant literature on PGE1 was reviewed along with personal experience with 4,577 patients during a 7-year period. PGE1 was compared to other vasoactive drugs, such as papaverine, the mixture of papaverine and phentolamine or linsidomine alone. RESULTS: In Europe PGE1 was officially approved for the therapy of peripheral arterial occlusive disease of the lower limbs in 1984. The drug has direct relaxing effects on smooth muscle cells of vessels and cavernous bodies, shows inhibitory effects on platelet aggregation, on low-density lipoprotein entry into the vascular wall and on presynaptic noradrenaline release and, therefore, it prevents the progress of atherosclerosis. In erectile failure PGE1 shows a response rate of more than 70% and, compared to papaverine with phentolamine, a considerably lower risk of priapism (0.35% versus 6%, respectively) as well as of local fibrotic complications. Except for rare cases of blood pressure decrease, no systemic side effects were observed after intracavernous injection of PGE1. CONCLUSIONS: For self-injection therapy, PGE1 presently represents the most efficacious and safest drug. Ongoing trials with topical and especially intraurethral PGE1 are promising and may offer less invasive therapies in the near future.

Alprostadil↗
PubMed1996

Prostanoid production in rabbit corpus cavernosum: I. regulation by oxygen tension.

PURPOSE: To investigate the effects of oxygen tension on prostanoid synthesis in rabbit penile corpus cavernosum tissue (RCC) in organ culture. MATERIALS AND METHODS: Strips of rabbit corpus cavernosum were incubated in organ culture media under varying oxygen conditions (0%, 12% and 21% oxygen), in the presence or absence of acetylcholine and arachidonate stimulation. Prostanoids were measured in collected media by radioimmunoassay. Prostaglandin H synthase (PGHS) protein levels and mRNA PGHS expression were measured under both 0% and 21% oxygen conditions. RESULTS: Basal and acetylcholine-stimulated PGI2 release was progressively diminished as a function of diminishing oxygen tension (pO2 from approximately 165 to 25 mm.Hg). The basal and stimulated production of other prostanoids, thromboxane A2, PGF2alpha, and PGE2, was also significantly inhibited under 0% oxygen (approximately 25 mm.Hg) conditions. However, incubation under 0% oxygen did not alter PGHS protein levels nor mRNA PGHS expression. Cavernosal strips incubated under 0% oxygen but supplemented with exogenous arachidonate (10 microM.) maintained significantly lower PGI2 production than tissues exposed to 21% oxygen (approximately 165 mm.Hg). CONCLUSIONS: These data demonstrate that oxygen tension regulates prostaglandin production in corporal tissue. The reduction in prostanoid production during hypoxia can be attributed to inhibition of PGHS activity rather than the expression of the enzyme. In view of the role of PGI2 as an inhibitor of platelet aggregation and white cell-endothelial adhesion, our findings may provide mechanistic insight into the alteration in corporal blood homeostasis ischemic-hypoxic priapism.

Acetylcholine↗
PubMed1994

Prostaglandin E1 in the medical management of erectile dysfunction in a genito-urinary medicine clinic.

Fifty consecutive patients with erectile failure who had previously proved refractory to papaverine and phentolamine intracavernosal therapy or were inappropriate candidates for such treatment were treated with intracavernosal prostaglandin E1. Forty patients (80%) achieved an erection sufficient for sexual intercourse and after a mean follow-up period of 5.9 months, 32 patients were continuing to use treatment successfully. The average dose was 14 micrograms (range 2.5 to 30 micrograms). There were no cases of priapism or cavernosal fibrosis and no systemic side effects. A low incidence (8%) of local discomfort was reported. We conclude that prostaglandin is a safe and effective vasoactive agent for the treatment of erectile failure in a genito-urinary outpatient clinic.

Adult↗
PubMed1996

Prostaglandin E1 with phentolamine for the treatment of erectile dysfunction.

AIM OF THE STUDY: to evaluate the feasibility of a self-injection programme for impotence with a combination of 10 micrograms prostaglandine E1 (PGE1) and 0.5 mg phentolamine. METHOD: follow-up at outpatients department with history taking, physical examination and questionnaires of 58 patients using this combination. Many patients could compare this drug combination with previously used drugs for intracavernous use. RESULTS: 42 patients started regular use. After a follow-up of 14 months, 26 are still on the programme. Drug related problems encountered: 10 patients reported insufficient erectile response, five patients have had priapism, four patients experienced severe pain, one patient developed fibrosis. CONCLUSION: the combination of PGE1 and phentolamine is very effective. The complication rate is comparable with those reported from PGE1 alone and from papaverine with phentolamine.

Adrenergic alpha-Antagonists↗
PubMed1996

Pharmacotherapy in erectile dysfunction agents for self-injection programs and alternative application models.

Previously, men with erectile dysfunction (ED) were frequently treated with penile prosthesis implants or considered to have psychogenic impotence. Since the reports by Virag and Brindley in 1932 and 1983, pharmacotherapy, by self-injection programs has become a new therapeutic concept for impotent men. In clinical practice, this application model has been generally accepted as the "golden standard" in the treatment of ED. Papaverine was first used as monotherapy, but because of side-effects such as prolonged erection, priapism, and fibrosis of the corpus cavernosum, single use of the drug was abandoned. Instead, papaverine was introduced in mixtures, e.g. together with alpha adrenoceptor-blockers as phentolamine, and/or prostaglandin E1 (PGE1) in these "cocktails", the dose of papaverine is reduced to 10-15 mg compared to the high doses (80-120 mg) that were used initially. By having two or more drugs in the mixture, a facilitating cascade effect as probably obtained. PGE1 is the only drug that has been approved by the FDA and is today registered in more than 50 countries. Other combination therapies such as vasoactive intestinal polypeptide+ phentolamine, or calcitonin gene-related peptide+ PGE1, have been suggested as suitable alternatives for intracavernosal injection. Transdermal and intraurethral application models may be considered in selected patients. Recently, oral administration of a phosphodiesterase inhibitor (UK-92.480) was reported to improve penile erection in patients with psychogenic impotence. Further clinical results from controlled trials will probably explain if this new oral drug will compete with PGE1 or other agents in self-injection programs.

Erectile Dysfunction↗
PubMedDate not supplied

[PGE1 program in erectile dysfunction: etiopathogenic and pharmacologic aspects].

Since Ishii et al.2 first described in 1986 the use of PGE1 in erectile dysfunction, a number of studies have been conducted using this vasoactive drug. Use in self-injecting programs, without additional drugs associated due to the ease of use and minimal complications, is currently becoming increasingly common as the choice therapy for erectile dysfunction. The paper analyzes our series of 66 patients included in self-injecting programs with PGE1 with no other drugs associated. Follow-up time has been 9.8 months (1-39). Mean age of our patients was 55. Our larger etiological groups were vascular (42%), diabetic (19%) and psychological (21%) patients. Dose increase over time has been significant in vascular and diabetic patients relative to the other groups. It has been found that program compliance has basically depended on the severity of the causative disease, which was significant in vascular and diabetic patients. Local complications have been: pain (19.6%), prolonged erection (3%), and priapism (1.5%).

Adult↗
PubMed1996

A pilot study of the role of intracavernous injection of vasoactive intestinal peptide (VIP) and phentolamine mesylate in the treatment of erectile dysfunction.

Twenty men with chronic impotence with a mean age of 46 years (range 26-63 y) were treated with self administration of 0.35 ml of Vasopotin 1 and 2, a combination of 30 mg Vasoactive Intestinal Peptide (VIP) and either 1.0 or 2.0 mg Phentolamine Mesylate. All patient were assessed using a standard protocol which included history and examination, vibratory penile biothesiometry, colour flow duplex Doppler ultrasonography and where indicated, Rigiscan nocturnal penile tumescence testing, dynamic infusion cavernosometry and cavernosography (DICC) and angiography. Impotence was classified as psychogenic in six patients, arteriogenic in nine patients, neurogenic in two patients and cavernosal venous leakage in three patients. A total of 60 injections was given. After sexual stimulation, an erection of sufficient rigidity for intercourse occurred in six patients with psychogenic impotence, seven of the nine patients with arteriogenic impotence, two patients with neurogenic impotence and one of three patients with cavernosal venous leakage. No patients experienced priapism, two patients complained of postinjection penile pain and three patients experienced transient facial flushing. Intracavernous self injection of Vasopotin appears to be a useful treatment for erectile dysfunction.

Adult↗
PubMed1996

[Prolonged use of moxisylyte chlorhydrate (Icavex) by intracavernous self-injections in the treatment of impotence. Evaluation of long-term tolerance].

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.

Adrenergic alpha-Antagonists↗