Over 150 million people worldwide are affected by erectile dysfunction. Alprostadil is an approved second-line treatment for erectile dysfunction (oral phosphodiesterase-5 inhibitors, for example, sildenafil, is the first line therapy). Alprostadil can be used in combination with other medications, the combination of papaverine, phentolamine, and alprostadil, known as "trimix," is particularly effective when used for intracavernous injection as a treatment for erectile dysfunction. However, it is only available from pharmacies authorized to produce such mixtures as it is otherwise not produced commercially.
Alprostadil is also used for the temporary ductus arteriosus patency maintenance in heart conditions where duct patency is mandated for survival until the defect is corrected surgically. The defects are both cyanotic (e.g., TGA - transposition of great vessels, TOF - tetralogy of Fallot, tricuspid atresia, pulmonary stenosis, etc.) and acyanotic (eg., coarctation of the aorta, interruption of the aortic arch). Alprostadil IV is FDA-approved for the temporary maintenance of patency of ductus arteriosus in neonates with ductal-dependent congenital heart disease until surgery. Alprostadil causes vasodilation by a direct effect on vascular and ductus arteriosus smooth muscle. In infants exhibiting restricted systemic blood flow, alprostadil can increase systemic blood pressure, and decrease the pulmonary artery pressure to aortic pressure ratio. Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. Lipo-PGE1 can effectively improve the neural function of patients with DPN.
Topical alprostadil has also shown promising results for the treatment of FSAD (female sexual arousal disorder) when used in a clinic on females with female sexual arousal disorder, but the more studies are needed to further define a proper role of topical alprostadil in the treatment of FSAD. Alprostadil is widely used to manage ischemic changes in patients with Raynaud phenomena. Prostaglandin E1 analogs have shown to be efficacious as a modality for conservative treatment for the patients with lumbar spinal canal stenosis. Contrast-induced nephropathy (CIN) is one of the top five leading cause of hospital-acquired acute renal injury, using alprostadil has shown to reduce the precontrast serum creatinine (SCr), blood urea nitrogen (BUN) levels and a decrease in the incidence of contrast-induced nephropathy (CIN).
Alprostadil is a synthetic analog of prostaglandin E1 and shows a multifariousness of pharmacologic actions. Alprostadil binds as an agonist to prostaglandin receptor which in turns activates adenylate cyclase leading to accumulation of 3'5'-cAMP (cyclic adenosine monophosphate) which is responsible for the pharmacologic effects of the medication including smooth muscle relaxation, causing vasodilation (increasing peripheral blood flow; helps in erectile dysfunction) and bronchodilation, and inhibits platelet aggregation.
When used as MUSE (medicated urethral system for erection):
Side effects of alprostadil on intracavernosal use:
Side effects of prostaglandin E1 analog (alprostadil) on intravenous use:
When starting alprostadil for a patient complaining of erectile dysfunction, certain things are to be kept in mind to prevent and for the early identification of adverse effects for better overall outcomes. Alprostadil is known to cause hemodynamic instability causing hypotension/hypertension, and flushing. It is advisable to monitor blood pressure, heart rate, and temperature, before and after the use of the drug. Alprostadil is also known to cause penile pathologies such as stricture formation, fibrosis, and hematoma formation at the site of infection. Regular examination by a physician and timely attention by one on the onset of discomfort can bring about better possible outcomes. For a better understanding of drug-to-effect response, monitoring the duration of erection can be essential for tailoring management for the patient.
Use of alprostadil for the treatment of erectile dysfunction in men is associated with prolonged erection, and sometimes priapism. The incidence of priapism as an adverse effect of alprostadil is more when used as 'MUSE,' and priapism is a genitourinary emergency that requires detailed evaluation. The evaluation is primarily based on physical exam and possibly with the help of penile ultrasonography and penile blood gas analysis. Some of the management techniques include aspiration of cavernosal blood, cold saline irrigation and penile injections with sympathomimetic agents. Penile prosthesis implantation for priapism are also commonly used.
Managing erectile dysfunction with alprostadil as an intracavernosal injection or as 'MUSE' requires an interprofessional team of healthcare providers, including a nurse, pharmacist, and several physicians in different specialties. Apart from classical causes of erectile dysfunction such as diabetes, hypertension, other common lifestyle factors such as obesity, limited or absence of physical exercise, lower urinary tract system infections are also linked to the development of erectile dysfunction requiring attention. Without proper management and patient education, the morbidity associated with the treatment itself can be dreadful. Patient education for the use of alprostadil as intracavernosal injection form or as 'MUSE' is a must and is an essential aspect of the management. The patient should be monitored timely for the adverse effects of the drug such as prolonged erection/priapism, penile fibrosis, urethritis, and penile fibrosis or stricture formation and circulatory disturbances causing hypotension. Consult with a radiologist, urologist to assess any penile pathology before starting alprostadil. Consult with a psychiatrist to evaluate for possible psychiatric issues that might cause erectile dysfunction. Consult a sex therapist for holistic management of erectile dysfunction. Consult a cardiologist as studies have shown an association of cardiovascular diseases with erectile dysfunction, whereas ED can be a strong indicator of CAD (coronary artery disease), and the recommendation is for cardiovascular assessment of a noncardiac patient in a patient coming with the chief complaint of erectile dysfunction. Also using alprostadil can cause circulatory issues causing hypotension.
Patients discussing reproductive health, particularly men, can be challenging, and it is essential to be empathetic and maintain a professional attitude while establishing a rapport. Creating a positive and respectful approach for patient and provider, allows there to be an open discussion for subject matters such as erectile dysfunction.
|||Hanchanale V,Eardley I, Alprostadil for the treatment of impotence. Expert opinion on pharmacotherapy. 2014 Feb; [PubMed PMID: 24369066]|
|||Vieillard V,Eychenne N,Astier A,Yiou R,Deffaux C,Paul M, Physicochemical stability study of a new Trimix formulation for treatment of erectile dysfunction. Annales pharmaceutiques francaises. 2013 Sep; [PubMed PMID: 24075706]|
|||Coceani F,Olley PM,Bishai I,Bodach E,Heaton J,Nashat M,White E, Prostaglandins and the control of muscle tone in the ductus arteriosus. Advances in experimental medicine and biology. 1977; [PubMed PMID: 899912]|
|||Aykanat A,Yavuz T,Özalkaya E,Topçuoğlu S,Ovalı F,Karatekin G, Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease. Pediatric cardiology. 2016 Jan; [PubMed PMID: 26260095]|
|||Wu JD,Tao S,Jin X,Jiang LL,Shen Y,Luo Y,Zhang P,Lee KO,Ye L,Ma JH, PGE1 improves diabetic peripheral neuropathy in patients with type 2 diabetes. Prostaglandins [PubMed PMID: 27421690]|
|||Kielbasa LA,Daniel KL, Topical alprostadil treatment of female sexual arousal disorder. The Annals of pharmacotherapy. 2006 Jul-Aug; [PubMed PMID: 16757679]|
|||Marasini B,Massarotti M,Bottasso B,Coppola R,Del Papa N,Maglione W,Comina DP,Maioli C, Comparison between iloprost and alprostadil in the treatment of Raynaud's phenomenon. Scandinavian journal of rheumatology. 2004; [PubMed PMID: 15370722]|
|||Yoshihara H, Prostaglandin E1 Treatment for Lumbar Spinal Canal Stenosis: Review of the Literature. Pain practice : the official journal of World Institute of Pain. 2016 Feb; [PubMed PMID: 25612248]|
|||Zhang JZ,Kang XJ,Gao Y,Zheng YY,Wu TT,Li L,Liu F,Yang YN,Li XM,Ma YT,Xie X, Efficacy of alprostadil for preventing of contrast-induced nephropathy: A meta-analysis. Scientific reports. 2017 Apr 21; [PubMed PMID: 28432310]|
|||Neves-Zaph SR, Phosphodiesterase Diversity and Signal Processing Within cAMP Signaling Networks. Advances in neurobiology. 2017; [PubMed PMID: 28956327]|
|||Lea AP,Bryson HM,Balfour JA, Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction. Drugs [PubMed PMID: 8785470]|
|||Becher E, Topical alprostadil cream for the treatment of erectile dysfunction. Expert opinion on pharmacotherapy. 2004 Mar; [PubMed PMID: 15013930]|
|||Porst H, Transurethral alprostadil with MUSE (medicated urethral system for erection) vs intracavernous alprostadil--a comparative study in 103 patients with erectile dysfunction. International journal of impotence research. 1997 Dec; [PubMed PMID: 9442415]|
|||Mantovani F, Alprostadil plus Vacuum (VITARUM) in severe erectile dysfunction (ED). Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2017 Jun 30; [PubMed PMID: 28679188]|
|||Cacione DG,Macedo CR,Baptista-Silva JC, Pharmacological treatment for Buerger's disease. The Cochrane database of systematic reviews. 2016 Mar 11; [PubMed PMID: 26967103]|
|||Porst H, [Transurethral alprostadil administration with MUSE ( [PubMed PMID: 9738294]|
|||Podolej GS,Babcock C, Emergency Department Management Of Priapism. Emergency medicine practice. 2017 Jan; [PubMed PMID: 28027457]|
|||Yücel ÖB,Pazır Y,Kadıoğlu A, Penile Prosthesis Implantation in Priapism. Sexual medicine reviews. 2018 Apr; [PubMed PMID: 28916463]|
|||Shamloul R,Ghanem H, Erectile dysfunction. Lancet (London, England). 2013 Jan 12; [PubMed PMID: 23040455]|