Papaverine 30mg/2ml / Phentolamine 1mg/2ml solution for injection ampoules

L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) phosphodiesterase in smooth muscles, and it has been observed to increase intracellular levels of cAMP and cGMP. It induces coronary, cerebral, and pulmonary artery dilatation and helps to lower cerebral vascular resistance and enhance cerebral blood flow. Current pharmacological research has revealed that papaverine demonstrates a variety of biological activities, including activity against erectile dysfunction, postoperative vasospasms, and pulmonary vasoconstriction, as well as antiviral, cardioprotective, anti-inflammatory, anticancer, neuroprotective, and gestational actions. It was recently demonstrated that papaverine has the potential to control SARS-CoV-2 by preventing its cytopathic effect. These experiments were carried out both in vitro and in vivo and require an extensive understanding of the mechanisms of action. With its multiple mechanisms, papaverine can be considered as a natural compound that is used to develop therapeutic drugs. To validate its applications, additional research is required into its precise therapeutic mechanisms as well as its acute and chronic toxicities. Therefore, the goal of this review is to discuss the major studies and reported clinical studies looking into the pharmacological effects of papaverine and the mechanisms of action underneath these effects. Additionally, it is recommended to conduct further research via significant pharmacodynamic and pharmacokinetic studies.

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Erectile dysfunction (ED) is a urological condition defined as the inability of a man to achieve or maintain an erection. This condition negatively affects his sexual performance and the performance of his partner. Phosphodiesterase type 5 (PDE5) inhibitors are commonly used to treat ED. Arginase II plays an important role in regulating L-arginine to NO synthase in the smooth muscle of the human corpus cavernosum of the penis. NO is a molecule essential for regulating a variety of functions, including arterial blood pressure, penile erection, and energy balance. Substances such as vardenafil, alprostadil, papaverine, and resveratrol increase NO production, thereby supporting sexual function and vascular health. Additionally, NO donors such as L-arginine, L-citrulline, and α-lipoic acid provide effective alternatives when used in combination with PDE5 inhibitors. Medications used in the treatment of ED include vardenafil, alprostadil, and papaverine. In addition, although molecules such as L-arginine, citrulline, resveratrol, alpha-lipoic acid, and rutin are thought to play a role in ED, their pharmacological and molecular effects have not been sufficiently elucidated. The aim of this study was to investigate the effects of these molecules in the treatment of ED by computer-based calculations, to obtain new information about them and to inspire new treatment strategies for ED. The physicochemical, molecular and pharmacokinetic properties of the compounds were determined by SwissADME software, and ADMET (absorption, distribution, metabolism, excretion and toxicity) data were determined by ADMETlab 3.0 software. Biological target and activity data were obtained by MolPredictX and PASS Online software. While the Gaussian 09 program was used for DFT calculations, PyMOL, AutodockTools 4.2.6, AutoDock Vina, and Biovia Discovery programs were used for molecular docking studies. It was found that L-arginine, citrulline, resveratrol and α-lipoic acid were well absorbed from the intestine, while rutin showed limited absorption. When their metabolic risks were evaluated, L-arginine and citrulline were found to have lower toxicity. Molecular docking results of rutin and resveratrol were remarkable. The electronic properties of the compounds were explained by DFT calculations. L-arginine and citrulline were found to have low toxicity and positive therapeutic effects. L-arginine and citrulline stand out as promising candidates for future research. Although resveratrol data are promising, unfortunately their potential toxicity and metabolic interactions require further investigation. It is important to learn more about these compounds or conduct research to improve their therapeutic efficacy. Although computer-based calculations play an important role in toxicity predictions, drug interactions, pharmacokinetics and toxicity properties should be carefully evaluated.

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Key Clinical Message: Topical papaverine is an effective vasodilator that can be used for dilating small veins to accept venous couplers for thumb replantation. This technique corrects size mismatches for successful venous anastomosis and minimizes postoperative complications. Abstract: Thumb replantation is a complex microsurgical procedure used to restore function and appearance after amputation. A successful venous anastomosis is essential in replantations; however, venous couplers can mismatch the size of veins and lead to obstacles. A 26-year-old male presented with a left thumb amputation caused by an electric saw injury. The amputated thumb was preserved and replantation surgery was performed 9 h post-injury. The digital artery and veins were repaired but a size mismatch was found between the only salvageable superficial vein (0.7 mm) and the smallest available venous coupler (1 mm). The vein was dilated to accept the coupler by a series of applications of topical papaverine (1 mg/mL). This allowed venous anastomosis to be accomplished in 25 min. Postoperative follow-up showed good thumb function, sensation, and circulation. Venous anastomosis is vital in thumb replantation to avoid venous congestion hence survival of the replanted thumb. Venous couplers shorten operative time and decrease the risk of postoperative complications. Papaverine is a vasodilator and facilitates venous anastomosis when veins and couplers are mismatched. This case demonstrates how papaverine, a vasodilator, may be used to improve surgical outcome during thumb replantation when small veins prevent venous coupler use.

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This study aimed to elucidate the vasodilatory effects and cytotoxicity of various vasodilators used as antispasmodic agents during microsurgical anastomosis. Rat smooth muscle cells (RSMCs) and human coronary artery endothelial cells (HCAECs) were used to investigate the physiological concentrations and cytotoxicity of various vasodilators (lidocaine, papaverine, nitroglycerin, phentolamine, and orciprenaline). Using a wire myograph system, we determined the vasodilatory effects of each drug in rat abdominal aortic sections at the concentration resulting in maximal vasodilation as well as at the surrounding concentrations 10 min after administration. Maximal vasodilation effect 10 min after administration was achieved at the following concentrations: lidocaine, 35 mM; papaverine, 0.18 mM; nitroglycerin, 0.022 mM; phentolamine, 0.11 mM; olprinone, 0.004 mM. The IC50 for lidocaine, papaverine, and nitroglycerin was measured in rat abdominal aortic sections, as well as in RSMCs after 30 min and in HCAECs after 10 min. Phentolamine and olprinone showed no cytotoxicity towards RSMCs or HCAECs. The concentrations of the various drugs required to achieve vasodilation were lower than the reported clinical concentrations. Lidocaine, papaverine, and nitroglycerin showed cytotoxicity, even at lower concentrations than those reported clinically. Phentolamine and olprinone show antispasmodic effects without cytotoxicity, making them useful candidates for local administration as antispasmodics.

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INTRODUCTION: The issue of sexual dysfunction in infertile couples is often neglected and underreported. As sexual dysfunction can both contribute to and result from infertility, clinicians should be equipped to identify and address these issues as part of comprehensive fertility care. OBJECTIVES: To develop evidence- and consensus-based recommendations for the clinical management of male sexual dysfunction (MSD) in the context of infertility. METHODS: Initial recommendations were formulated based on expert opinion and exploratory analysis of various types of MSD associated with infertility. A focused literature review was conducted for each topic, followed by iterative rounds of expert discussion to refine recommendations. Final consensus was achieved at the 5th International Consultation on Sexual Medicine meeting, and recommendations were rated using GRADE criteria. RESULTS: MSD and infertility often coexist, necessitating a detailed sexual history and physical examination during the initial infertility evaluation. Erectile dysfunction may be effectively managed with counseling, phosphodiesterase-5 inhibitors, or intracavernosal injections (eg, alprostadil, papaverine, phentolamine), which do not impair fertility outcomes. For low libido or unconsummated marriages, a multidisciplinary approach tailored to the couple's priorities-sexual function or fertility-is recommended. Ejaculatory disorders may be treated with counseling, penile vibratory stimulation, electro-ejaculation, medications, or assisted reproduction, depending upon the underlying cause. Selective serotonin reuptake inhibitors, used for premature ejaculation, may adversely affect sperm parameters and should be prescribed cautiously. Men with hypogonadism seeking fertility should avoid exogenous testosterone; alternatives such as selective estrogen receptor modulators, aromatase inhibitors, or gonadotropins may be considered. Lifestyle optimization, management of comorbidities, and use of fertility-safe lubricants can improve sexual and reproductive outcomes for couples trying to conceive. CONCLUSION: MSD and infertility are often interrelated. Incorporating routine sexual health assessments into fertility evaluations enables clinicians to diagnose and treat MSD effectively, thereby improving both sexual function and reproductive success.

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OBJECTIVE: To describe a case of clinically significant norepinephrine extravasation in a dog with a successful outcome following the use of subcutaneous phentolamine infusion. CASE SUMMARY: An 8-year-old male neutered Labrador Retriever experienced norepinephrine extravasation from a cephalic, peripheral intravenous catheter while under anesthesia for an exploratory laparotomy. Upon recognition of norepinephrine extravasation, moderate subcutaneous edema and a painful dermal plaque were apparent at the extravasation site. Ten milligrams of phentolamine mesylate, a potent alpha-adrenergic receptor antagonist, were diluted in 10 mL of sterile saline and administered subcutaneously in small aliquots at multiple sites in the area of extravasation. The patient remained hemodynamically stable during and after the infusion. Most phentolamine injections produced instantaneous erythematous macules that resolved 24-36 h later, and the integument in the extravasation area rapidly changed from a "blanched" to a "pink" color. The subcutaneous edema gradually resolved within 7 days post-extravasation. At 12 h following extravasation, the dermal plaque progressed into a necrotic focus, which later developed into an ulcer (36 h), then a small crust (7 days), and finally healed epidermis (9 days). When the patient was euthanized 10 days after surgery due to continued decline secondary to systemic disease, there remained only a small superficial crust at the site of extravasation. UNIQUE INFORMATION: To the authors' knowledge at the time of submission, this case report documented the first reported clinical use of subcutaneous phentolamine infusion for the management of norepinephrine extravasation in a veterinary species.

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We present a case of medication-induced priapism that was refractory to conventional urologic methods and required treatment with a caverno-saphenous bypass. The patient had been misusing an injectable erectile dysfunction medication consisting of alprostadil, papaverine, and phentolamine (Trimix), resulting in multiple episodes of priapism. His initial episodes of priapism were successfully treated with the traditional urologic algorithm, including phenylephrine, aspiration, and distal shunting. However, due to his continued medication misuse, these became ineffective, requiring proximal shunt surgery. Priapism requiring an extra-anatomic bypass is exceedingly rare. Following our proximal shunt surgery, he maintained partial sexual function, and his bypass remained patent.

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