Case Report
 

By Prof. Hari Aggarwal , Dr. Deepak Jain , Dr. Raj Kawar Yadav
Corresponding Author Prof. Hari Aggarwal
Department of Medicine, University of Health Sciences, - India 124001
Submitting Author Prof. Hari Aggarwal
Other Authors Dr. Deepak Jain
Deptt.of Medicine Pt BDS PGIMS Rohtak, - India

Dr. Raj Kawar Yadav
Pt BDS PGIMS Rohtak, - India

PHARMACOLOGY

Phosphodiesterase enzyme inhibitors , Sildenafil, Priapism

Aggarwal H, Jain D, Yadav R. Priapism Induced With Single Oral Dose Of Sildenafil: A Rare Case Report. WebmedCentral PHARMACOLOGY 2010;1(9):WMC00676
doi: 10.9754/journal.wmc.2010.00676
No
Submitted on: 20 Sep 2010 04:27:17 PM GMT
Published on: 20 Sep 2010 05:21:25 PM GMT

Abstract


Phosphodiesterase enzyme inhibitors like Sildenafil citrate and tadalafil has revolutionised the treatment of erectile dysfunction. Priapism as a side effect of Sildenafil has been reported very rarely. We report a case of priapism caused by usual dose of Sildenafil

CASE REPORT


A 25 years old married healthy male presented in emergency department with history of priapism of 72 hours duration after consuming a non-prescribed single tablet of sildenafil (50 mg) purchased over the counter along with 250ml of alcohol. He developed painful priapism 30 minutes after drug intake, when he was viewing pornographic material for sexual stimulation. There was no history of intake of any priapism inducing drugs like antihypertensive or antipsychotics or any other drugs that affect the metabolism of Sildenafil. There was no history suggestive of sickle cell trait, leukemia or multiple myeloma.
Haemogram, coagulation parameters and serum chemistry were all within normal limits. Work up for sickle cell trait was negative.
On examination, the corpus spongiosum and glans was soft and the corpus cavernosa was rigid. Patient was reluctant for any kind of surgical intervention and insisted for oral medication. On repeated perusation, aspiration and corporal wash followed by a winter procedure were done but with no relief. Fifteen milliliters of dark blood was aspirated with 16 G needle. Consent was taken after explaining the negligible chance of regaining potency for proximal caverno-spongiosal shunting but patient refused for any surgical intervention and left the hospital against medical advice. Further follow up could not be done.

DISCUSSION


Priapism is defined as a genuine erectile disorder, in which erection persists uncontrollably without sexual purpose. The significance of priapism is further emphasized by the fact that this disorder commonly causes erectile tissue damage and leads to the loss of functional erections. Hematologic dyscrasias like sickle cell disease, thrombophilia and thalassemia have been associated with priapism. Hematologic malignancies including leukemia and multiple myeloma have also been identified for their risk associations with this disorder.1
The identification of the cyclic GMP/NO pathway as the final neurotransmitter messengers responsible for penile erection and the subsequent development of highly specific phosphodiesterase enzyme inhibitors like sildenafil has revolutionised the treatment of erectile dysfunction. Sildenafil citrate and tadalafil citrate are effective, well tolerated and safe treatments for erectile dysfunction caused by a broad range of aetiologies.2-3 Sildenafil though has no direct relaxant effect on isolated human corpus cavernosum, but it enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum.4-5 Sildenafil at recommended doses has no effect in the absence of sexual stimulation.  Sildenafil has been reported to restore sexual activity in low-flow priapism, recurrent priapism, corporal fibrosis associated with recalcitrant priapism and as a preventative strategy for priapism. Sildenafil has also been used to relieve priapism in patients with sickle cell disease.6-9
Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. In addition to the active ingredient, , each tablet contains the inactive ingredients like: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake. There may be a hypersensitivity to any component of the tablet. For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. The onset of activity of sildenafil is 14 min. The peak plasma levels are attained within 30 to 120 min (median 60 min) of oral dosing in the fasted state. It is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41%. It is eliminated predominantly by hepatic metabolism (mainly cytochrome P450 3A4) and is converted to an active metabolite with properties similar to the parent, sildenafil. Both sildenafil and the metabolite have terminal half lives of about 4 h. sildenafil clearance is reduced in severe renal impairment or hepatic cirrhosis.. The concomitant use of potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole) as well as the nonspecific CYP inhibitor, cimetidine, is associated with increased plasma levels of sildenafil. Side effects like back pain, flu syndrome, arthralgia., hyperglycemia, paresthesia, tremor dyspepsia, photosensitivity reaction, abdominal pain, syncope, tachycardia, palpitation, anemia and leukopenia are observed .Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely.10
An extensive review of the published medical literature and the manufacturer's clinical trial and post marketing database identified six reports of priapism following the use of sildenafil in an estimated 1.2 billion users.11-14 The earlier reports of priapism following the use of sildenafil have been with self-administration of very large doses or in conditions predisposing to priapism or had used drug for prolonged period.. The first case report of priapism induced by oral sildenafil was due to a high dose (200mg)15. Priapism may also follow simultaneous oral dose and intracavernous injection. of alprostadil or trimix.11 Recently, an accidental consumption of six 50 mg tablets (up to 30 mg/kg) in a 19-month-old child resulting in facial flushing and priapism has been reported.15 Priapism following the use of sildenafil in safe oral doses for a healthy individual has been reported earlier but very rarely; 17-19
Our patient had priapism following a single dose of the usually prescribed dosage of 50 mg and had no predisposing condition. Although he has consumed tablet with alcohol, however extensive review of literature does not show any interaction between alcohol and sildenafil. Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. On the contrary in a recent study it is reported that sildenafil dramatically reduces alcohol-induced gastric damage in rats. The authors provide convincing evidence that such protection not only occurs via the nitric oxide (NO)/cGMP pathway, but also involves regulation of ATP-sensitive potassium channels20.
An escalating dose starting at 12.5 mg and then increasing to 25 mg and followed by the usual prescribed dose of 50 mg may help to avoid the side effects of priapism. [4] This case highlights the existence of unfortunate myths surrounding the omnipotence of Sildenafil, in all sorts of sex related problems. It points toward an urgent need for steps to prevent unauthorized prescription and misuse of this drug. It should only be used under professional guidance as abuse of such drug may lead to severe morbidity. It is difficult to predict which individuals are more prone to develop priapism, though a genetic basis with cross-reactivity of PDE-3 in addition to PDE-5 resulting in a cumulative erection effect may be possible elucidation. In the eventuality of only few case reports, highlighting this side effect of sildenafil, it is difficult to draw concrete conclusion. Therefore more research directed towards the etiopathogenesis of this side effect of sildenafil is needed.

References


1. Burnett L. Therapy insight: priapism associated with hematologic dyscrasias. Nature Clinical Practice Urology (2005) 2,449-56.
2. Brock GB. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002; 168:1332.
3. Morales A. Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res 1998; 10:69.
4. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto GM, Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990;170:839-43
5. Lin CS, Lau A, Tu R, Lue TF. Expression of three isoforms of cGMP binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Commun 2000;268:628-35
6. Rajfer J, Gore JL, Kaufman J, Gonzalez CN. Case report: Avoidance of palpable corporal fibrosis due to priapism with upregulators of nitric oxide. J Sex Med 2006;3:173-6.       
7. De Rose AF, Corbu C, De Caro G, Bonini F, Carmignani G. Priapism: Decisional algorithm, our experience, and role of sildenafil in sexual rehabilitation. Arch Ital Urol Androl 2001;73:27-32.       
8. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Long term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism. Urology 2006;67:1043.
9. Bialecki ES, Bridges KR. Sildenafil relieves priapism in patients with sickle cell disease. Am J Med 2002;113:252.
10. The Internet Drug Index (online) 2010. Available from URL:/http://www.rxlist.com/ impotence_ed/article_htm.
11. Sur RL Kane CJ. Sildenafil citrate associated priapism. Urology 2000;55:950.
12. Aoyagi T, Hayakawa K, Miyaji K, Ishikawa H, Hata M. Sildenafil induced priapism.    Bull Tokyo Dent Coll 1999;40:215-7. 
13. Kassim AA, Fabry ME, Nagel RL. Acute priapism associated with the use of sildenafil in a patient with sickle cell trait. Blood 2000; 95:1878.
14. Goldmeier D, Lamba H. Prolonged erections produced by dihydrocodeine and sildenafil. BMJ 2002; 324:1555.
15. McMahon CG. Priapism associated with concurrent use of phosphodiesterase inhibitor drugs and intracavernous injection therapy. Int J Impot Res 2003;15:383-4.       
16. Wills BK, Albinson C, Wahl M, Clifton J. Sildenafil citrate ingestion and prolonged priapism and tachycardia in a pediatric patient. Clin Toxicol (Phila) 2007;45:798-800.       
17. Kumar R, Jindal L, Seth A. Priapism following oral sildenafil abuse. Natl Med J India 2005;18:49.
18. Adhikary S, Sinha M, Chacko KN. Sildenafil induced priapism. Indian J Urol 2006;22:146-7.
19. Sharma S, Panda S, Sharma S, Singh SK, Seth A, Gupta N. Prolonged priapism following single dose administration of sildenafil: A rare case report. Urol Ann 2009;1:67-8.
20. Duffin R, Shaw CA, Rossi AG. Sildenafil reduces alcohol induced gastric damage: just say ‘NO'. Br J Pharmacol 2008 April 14; 153(8):1764.

Source(s) of Funding


No funding,  No conflict of interest

Competing Interests


No competing interests

Disclaimer


This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

Reviews
2 reviews posted so far

Sildenafil Priapism
Posted by Dr. Bennett N on 21 Jan 2011 06:48:42 PM GMT

Comments
0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.

 

Author Comments
0 comments posted so far

 

What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
Where
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)