Guideline for oral healthcare of adults with Huntington's disease Graham Manley1, Helen Lane1, Annette Carlsson2, Bitte Ahlborg2, Åsa Mårtensson2, Monica B Nilsson2, Sheila A Simpson3,4 & Daniela Rae*3,4; On behalf of the contributing members of the European Huntington's Disease Networks Standards of Care Dental Care Group A preventive dentistry regime should be implemented at the earliest possible opportunity and maintained throughout development of the condition. The use of high fluoride toothpaste is essential.
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Repository.uobaghdad.edu.iqOriginal Article Dermatological side effects of Sildenafil among a group of Iraqi males Nadheer A. Matloob Dermatological Side Effects of Sildenafil among a group of Iraqi
Nadheer A. Matloob* MBCHB, DDV, FICMS, CABD
Background: Sildenafil is a drug that is used to treat erectile dysfunctions, it acts by inhibiting CGMP
specific phosphodiesterase type 5, an enzyme that regulates blood flow in the penis. The most common
adverse effects of sildenafil are headache, dyspepsia, nasal congestion and impaired vision which
includes photophobia and blurred vision. Many dermatological side effects are present like flushing,
Fac Med Baghdad urticaria, sweating and many others. 2010; Vol. 52, No.4 Patients and Methods: Fifty six males were included in this study, with ages between 37 – 60 years and
Received Mar.2010 a mean age of 50.1 ± 7.1years. The study was conducted from November 2004 till May 2009 in the Accepted Nov. 2010 Department of Dermatology of Al-Kadhymia Teaching Hospital in Baghdad; all patients experienced dermatological side effects every time they use the drug. Full history and full examination including
dermatological examination were done for all patients.
Results: The commonest dermatological side effect was flushing of the face which was seen in 44
(78.6%) patients followed by hyperhydrosis which was seen in 14 (25%) patients then urticaria which
was seen in 12 (21.4%) patients. It is seemed that side effects were more with 100mg dose than with
50mg dose (78 side effect against 22 one) and this result was statistically significant.
Conclusion: Dermatological side effects of sildenafil are fairly common and dermatologist must be
aware of these side effects especially when he searches for the cause of angioedema, urticaria, pruritis as
well as erythroderma.
Keywords: Sildenafil, Dermatological, Side effects.
Sildenafil citrate, sold as Viagra and under various
dysfunction in all settings,including diabetes.(4)People other trade names, is a drug that is used to treat erectile on antidepressants may experience sexual dysfunction, dysfunctions in males. It was developed and being either as a result of their illness or as a result of their marketed by the pharmaceutical company Pfizer. Since treatment and a study showed that sildenafil improved 1998, sildenafil has been the prime treatment for sexual function in men in this situation. (5) The same erectile dysfunction and it is frequently called the 'blue researchers found that sildenafil was able to improve pill'.(1) The mechanism of action of sildenafil citrate the sexual function in female patients on involves the release of nitric oxide (NO) in the corpus antidepressants as well. (6, 7) Other common cavernosum of the penis, this NO binds to the indications include pulmonary hypertension and receptors of the enzyme guanylate cyclase which altitude sickness. (8, 9) The dose of sildenafil for results in increased levels of cyclic guanosine erectile dysfunction is 25 mg to 100 mg taken not monophosphate (CGMP), leading to smooth muscle more than once per day between 30 minutes and 4 relaxation (vasodilatation) of the intimal cushions of hours prior to sexual intercourse.(10) the helicine arteries, resulting in an increased inflow of Contraindications include those who use organic blood into the spongy tissue of the penis causing an nitrites and nitrates, such as glyceryl trinitrate erection . (2) Sildenafil is a potent and selective (nitroglycerin), sodium nitroprusside, amyl nitrite inhibitor of CGMP specific phosphodiesterase type 5 ("poppers"),(11) also men for whom sexual intercourse (PDE5) which is responsible for degradation of CGMP is inadvisable due to cardiovascular risk factors, in the corpus cavernosum.(3) The molecular structure Severe hepatic impairment (decreased liver function), of sildenafil is similar to that of CGMP and acts as a Severe impairment in renal function, Hypotension competitive binding agent of PDE5 in the corpus (low blood pressure), Recent stroke or heart attack, cavernosum, resulting in more CGMP and better Hereditary degenerative retinal disorders (including erection. (2, 3) Uses of sildenafil citrate include Sexual genetic disorders of retinal phosphodiesterases). The dysfunction; the primary indication of sildenafil is most common adverse effects of sildenafil include treatment of erectile dysfunctions (inability to sustain a headache, flushing, dyspepsia, nasal congestion and satisfactory erection to complete intercourse). It is impaired vision (including photophobia and blurred used now as a standard treatment for erectile vision).(12) Some sildenafil users have complained of seeing everything tinted blue (cyanopsia).(13) Some *Dept. of Dermatology and Venereology, Al-Nahrain complained of blurriness and loss of peripheral vision College of Medicine and it may lead to vision impairment in rare cases,(14) J Fac Med Baghdad 398 Vol.52, No.4, 2010 Dermatological side effects of Sildenafil among a group of Iraqi males Nadheer A. Matloob and a number of studies have linked sildenafil use with nonarteritic anterior ischemic optic Continuous variables were expressed as mean and neuropathy.(15, 16) Rare but serious adverse effects standard deviation. Categorical variables were found through post marketing surveillance include expressed as percentages. Descriptive characteristics priapism, severe hypotension, myocardial infarction, of patients were compared using χ2 tests with Yate's ventricular arrhythmias, stroke, increased intraocular correction for continuity. All database management pressure and sudden hearing loss. (12) As a result, the and statistical analyses were performed with SPSS FDA announced that the labeling for all PDE5 software (10th version). The level of significance was inhibitors, including sildenafil, required a more set at (P-value < 0.05).All probability values were prominent warning of the potential risk of sudden hearing loss. (17) Dermatological side effects include rash which was reported in at least 2% of patients and Results:
other side effects include urticaria, herpes simplex, Fifty six Iraqi males were included in this study, with pruritis, sweating, skin ulcer, contact dermatitis and ages between 37 & 60 years and a mean age of 50.1 ± exfoliative dermatitis. (18) Interactions Care should 7.1 years. Thirty eight (67.9%) of these patients were be exercised by patients who are also taking protease diabetics and the other 18 (32.1%) took the drug for inhibitors which inhibit the metabolism of sildenafil, different other causes including psychological effectively multiplying the plasma levels of sildenafil, problems. All patients had the same side effects every increasing the incidence and severity of side-effects. It time they took the drug, and the minimal number of is recommended that patients using protease inhibitors attacks at time of examination was three and some of limit their use of sildenafil to no more than one 25 mg those patients experienced the side effects many times dose every 48 hours. Concomitant use of sildenafil and monthly (at each time they took the drug), the attacks an alpha blocker may lead to low blood pressure, but appeared between few hours and 10 days from the this effect does not occur if they are taken at least four time of taking the drug depending on the type of the hours apart. (19) This study was designed to determine dermatological side effect, the earliest side effects to the dermatological side effects of Sildenafil among a be appear were flushing and urticaria which appeared group of Iraqi males. within few hours after taking the drug and the latest was maculo-papular rash which appeared after up to Patients and Methods:
10 days in many occasions. Some patients had more Fifty six Iraqi males were included in this study, with than one side effect and it is seemed that side effects ages between 37 & 60 years and a mean age of 50.1 ± were more with 100mg dose than with 50mg dose (78 7.1 years. The study was conducted between side effects appeared with 100mg dose against 22 side November 2004 & May 2009 in the Department of effects appeared with 50 mg) and this result was Dermatology of Al-Kadhymia teaching hospital in statistically significant (P value ≤ 0.0001 & Chi square Baghdad. Every one of the patients experienced = 60.5). The commonest side effect was flushing of the dermatological side effect every time he took the drug face which was seen in 44 (78.6%) patients followed and this side effect was documented after excluding by hyperhydrosis which was seen in 14 (25%) patients other causes of every one of the side effects. Full then urticaria which was seen in 12 (21.4%) patients history including age, occupation, the dose (and the (Table 1). Some of the side effects were sever and manufacture)of the drug when taken, the duration considered as emergencies like angioedema and between the ingestion of the drug and the appearance erythroderma. The patients used sildenafil tablets from of the dermatological side effect, history of other drugs different manufactures and experienced side effects in take, history of systemic and other illnesses, also from all of these including the original Pfizer full examination including dermatological examination manufacture and so the side effects are due to the drug were done for all patients by the same dermatologist. itself not to the manufacture. The drug was prescribed by different doctors from inside and outside the hospital including the researcher Table 1: Dermatological side effects of sildenafil
himself (as the drug is usually prescribed by many different medical branches) and the drug was obtained from different pharmacies including the hospital pharmacy. All patients attended the dermatology Hyperhydrosis 14 department due to the appearance of the same rash every time they took the drug and no one of them Pruritis 10 17.9 discovered accidentaly.Those 56 males took either 50 Maculopapular rash or 100 mg tablets and some of them took 50 mg and if he had no benefit then took a 100 mg tablet. The drug manufactures were multiple as some of those men took the standard Pfizer tablets others took tablets made by other manufactures as Indian Ranbaxy co. and even J Fac Med Baghdad 399 Vol.52, No.4, 2010 Dermatological side effects of Sildenafil among a group of Iraqi males Nadheer A. Matloob Discussion:
57. Retri Dermatological side effects were not mentioned in details previously in any study but seem to be fairly 2. Bolell M, Allen MJ, Ballard SA, Gepi-Attee S, common among Iraqi males, side effects other than the Muirhead GJ, Naylor AM, Osterloh IH, Gingell C. dermatological ones were fully determined but "Sildenafil: an orally active type 5 cyclic GMP- unfortunately they are still few in number and so our specific phosphodiesterase inhibitor for the treatment study considered as the first one to be done in Iraq and of penile erectile dysfunction". Int J Impot Res 1996; 8 may be the first one in the other different parts of the (2): 47–52. world regarding this aspect, however, it was 3. Terrett NK et al. Sildenafil (Viagra), a potent and previously mentioned that skin rash may appeared in selective inhibitor of Type 5 CGMP phosphodiesterase 2% of patients who took sildenafil (18) and this point with utility for the treatment of male erectile needs volunteers studies in Iraq similar to what dysfunction". Bioorg Med Chem Lett 1996; 6: 1819– occurred abroad. Dundar etal showed that flushing of the face was shown in 75% of the men that took 4. Vardi M, Nini A. "Phosphodiesterase inhibitors for sildenafil and this result is nearly similar to what's erectile dysfunction in patients with diabetes mellitus". appear in our study which showed that flushing Cochrane Database Syst Rev 2007; (1): CD002187. appeared in 78.6% of Iraqi males and flushing was the 5. Nurnberg HG, Hensley PL, Gelenberg AJ, Fava M, only dermatological manifestation that commonly Lauriello J, Paine S. Treatment of antidepressant- mentioned in the literature (21), however, it was associated sexual dysfunction with sildenafil: A mentioned in other studies that flushing appeared in randomized controlled trial. JAMA 2003 Jan; 289 (1): 10% of the patients only and this difference from our study may be due to the difference in patient's 6. Nurnberg HG, Hensley PL, Lauriello J, Parker LM, number, the difference in the used dose of the drug or Keith SJ (). Sildenafil for women patients with due to the little concentration on the dermatological antidepressant-induced sexual dysfunction. Psychiatr side effects in the literature. (18) Serv 1999 Aug; 50 (8): 1076–8. This study showed the appearance of dermatological 7. Nurnberg HG, Hensley PL, Heiman JR, Croft HA, side effects that did not mentioned in the literature as Debattista C, Paine S. Sildenafil treatment of women diffuse dermatitis and angioedema that may be with antidepressant-associated sexual dysfunction. severely affects the patients also other cutaneous side JAMA 2008; 300 (4): 395–404. effect may be life threatening like erythroderma and 8. Richalet JP, Gratadour P, Robach P et al. Sildenafil inhibits altitude-induced hypoxemia and pulmonary This study also showed that the higher the dose of the hypertension". Am. J. Respir. Crit. Care Med.2005; drug, the more the side effects will appear (78 side 171 (3): 275–81. effects appeared with 100 mg dose and only 22 with 9. Fagenholz PJ, Gutman JA, Murray AF, Harris NS. 50 mg dose) and the result was statistically significant, Treatment of high altitude pulmonary edema at 4240 this point was also not mentioned in the literature. It m in Nepal. High Alt. Med. Biol. 2007; 8 (2): 139–46. shown in this study that the drug itself and not the 10. Oh SS, Zou P, Low MY, Koh HL. Detection of manufacture seems to be the cause of the side effects sildenafil analogues in herbal products for erectile as drug from all known manufactures caused these dysfunction. Journal of Toxicology and Environmental 11. Venhuis BJ, Blok-Tip L, de Kaste D. Designer drugs in herbal aphrodisiacs. Forensic Science Dermatological side effects of sildenafil are fairly International. 20 May 2008; 177(2-3): e25-7. common and a dermatologist must be aware of them 12. "Pill Identifier". Drugs.com. especially when he searches for the cause of angioedema, urticaria, pruritis as well as erythroderma Retrieved 10-2-2009. and some of these side effects are serious and life 13. Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM . Use of sildenafil The higher the dose of the drug the higher the (Viagra) in patients with cardiovascular disease. incidence of the side effects will be seen. The drug itself and not the manufacture seems to be 33 (1): 273–82. the cause of the side effects as drug from all known 14."VIAGRA Prescribing Information" (PDF). Pfizer. manufactures caused these side effects. References:
1. Aubetawe Bro Morgannwg University NHS Trust 15. Pomeranz; Pomeranz HD and Bhavsar AR. (4-7-2008)."Research at ABM". Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases. J Neuroophthalmol 2005; 25 (1): 9–13. J Fac Med Baghdad 400 Vol.52, No.4, 2010 Dermatological side effects of Sildenafil among a group of Iraqi males Nadheer A. Matloob 16. Egan; Egan R and Pomeranz H. Sildenafil (Viagra) associated anterior ischemic optic neuropathy. Arch Ophthalmol 2000; 118 (2): 291–2. 17. Boshier A, Pambakian N, Shakir SA. A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil. Int J Clin Pharmacol Ther 18.http://www.drugs.com/sfx/viagra-side-effects.html 19. Akash R, Hrishikesh D, Amith P, Sabah S. Case report: association of combined nonarteritic anterior ischemic optic neuropathy (NAION) and obstruction of cilioretinal artery with overdose of Viagra. J Ocul Pharmacol Ther (2005); 24 (4): 315–7. 20. Duncan RC, Knapp RG, Miller MC (Eds). Introductory biostatistics for the health sciences, 1977, Wiley & Sons Inc.; PP: 79-85. 21. Dündar M, Koçak I, Dündar SO, Evaluation of side effects of sildenafil in group of young healthy volunteers. J Int Urol and Nephrol 2001 Dec; 32(4):705-708. J Fac Med Baghdad 401 Vol.52, No.4, 2010
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