Fixed drug eruption by etoricoxib confirmed by patch test

Abstract: Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Abstract The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

Systematic Review and Meta-Analysis of Pulmonary Hypertension Specific Therapy for Exercise Capacity in Chronic Obstructive Pulmonary Disease

Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.

Sequential, non-arteritic anterior ischemic optic neuropathy in patients taking sildenafil: a report of ten cases

To present a summary of 10 cases of non-arteritic anterior ischemic optic neuropathy [NAION] in patients who received phosphodiesterase type 5 [PDE-5] inhibitors. A case series of 10 patients who, after regular intake of Sildenafil, presented with a first episode of NAION in one eye. NAION was diagnosed based on the following criteria: acute, painless, unilateral loss of vision, fundus features consistent with NAION and exclusion of other possible causes. Despite the initial adverse event [first episode of NAION], all of these patients continued to use the medication and developed a second episode of NAION in the contralateral eye. Only one of the 10 patients presented with bilateral simultaneous NAION. This largest case series published to date, reinforces the general consensus that PDE-5 inhibitors are contraindicated in patients with a history of unilateral NAION.

Effect of sildenafil citrate on behavior and excitatory and inhibitory amino acids levels in albino rat's brain

Sildenafil is an active cGMP-specific phosphodiesterase type 5 inhibitor that is effective in the treatment of male erectile dysfunction. None of the previous studies have measured sildenafil or its possibly related neurochemical changes, but mainly they related their finding to sildenafil associated behavior changes. In this work, behavioral and brain neurochemical changes [excitatory and inhibitory neurotransmitters] associated with acute administration of sildenafil using male albino rats were investigated. Rats were divided into three groups [n=6]; group1 received saline [1ml/kg], group 2 received single doses of sildenafil [1.5mg/kg], while group 3 received single doses of sildenafil [100mg/kg]. Administration was via the intraperitoneal route. Behavior scores using EPM and brain homogenate for neurotransmitters evaluation by HPLC were carried out 60min after administration. Sildenafil did not produce any changes in behavior using the EPM test; also it did not alter the brain levels of excitatory, inhibitory and dopamine. Sildenafil produced dose dependent decreases in plasma dopamine level by mechanism[s] needs more neurochemical investigation. The chronic effect of sildenafil should be taken into consideration.

Evaluation the effect of sildenafil citrate [sc or viagra] on senile albino rat testis [histological and biochemical study]

Sildenafil citrate [SC or Viagra] is an oral medication widely used to treat erectile dysfunction and maintains a sufficient erection for satisfactory sexual performance. The side effects of sildenafil citrate have been reported. The present study was designed to investigate the effect of sildenafil citrate in the therapeutic dose in different regimes. This study included forty senile male albino rats divided into four equal groups. Group [A] was used as a control group [did not receive any treatment]. Group [B] receive the therapeutic dose of Viagra [1.5 mg suspended in 1.5 ml distilled water] orally using a gastric gavage as daily dose for one week. Group [C] received the therapeutic dose of Viagra 3 times / week for two weeks. Group [D] received the therapeutic dose of Viagra each week for 4 weeks. Half of the treated rats of the different groups were sacrificed, other half were sacrificed after two weeks from the last dose as recovery groups [RB, RC and RD]. The testes were dissected and blocked in paraffin. Hematoxylin and Eosin [HX and E] and Periodic acid Schiff stain [PAS] were applied and serum testosterone levels in the different groups were evaluated. The present study showed that the therapeutic dose of sildenafil caused several histological findings in the germinal epithelial of the rat testes including degeneration, detachment of the spermatogenic cells especially the primary spermatocytes with addition thickening of the basement membranes of the seminiferous tubules and increased interstitial Leydig cells. The serum testosterone of the treated rats showed increased level of testosterone especially in group D. The recovery rats showed relative improvement of parameter toward normal. Sildenafil produce morphological and histological alterations in the testes

Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: A randomised, double-blind, placebo-controlled trial.

Background. Sildenafil has been found to improve exercise capacity and haemodynamic parameters in patients with various pulmonary disorders. This study was undertaken to evaluate its efficacy in severe chronic obstructive pulmonary disease (COPD). Methods. In this double-blind, randomised, placebo-controlled study, 37 patients with severe COPD received either sildenafil or placebo for 12 weeks. Distance covered in six-minute walk test (6MWD) was taken as primary end-point. Pulmonary artery pressure (PAP) was measured as secondary end point. Results. Thirty-three patients (15 in sildenafil arm and 18 in placebo arm) completed the study. Non-parametric tests were used for comparison. There was significant increase in 6MWD from baseline after three months of follow-up in sildenafil users (median change in distance covered in six-minute walk test (Δ6MWD)=190m) as compared to placebo users (Δ6MWD=0m, p< 0.05). The PAP decreased significantly (χ2=14.94, p<0.05) in sildenafil group after three months, while it did not change significantly among placebo group (χ 2=3.84, p>0.05). Conclusion. Sildenafil improved 6MWD and PAP in patients with severe COPD. This trial has been registered with Indian Council of Medical Research (ICMR) Trial Registry. [CTRI Registry Number: CTRI/ 2009/091/000017]

Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats

Prostaglandins control osteoblastic and osteoclastic function under physiological or pathological conditions and are important modulators of the bone healing process. The non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and consequently prostaglandins synthesis. Experimental and clinical evidence has indicated a risk for reparative bone formation related to the use of non-selective (COX-1 and COX-2) and COX-2 selective NSAIDs. Ketorolac is a non-selective NSAID which, at low doses, has a preferential COX-1 inhibitory effect and etoricoxib is a new selective COX-2 inhibitor. Although literature data have suggested that ketorolac can interfere negatively with long bone fracture healing, there seems to be no study associating etoricoxib with reparative bone formation. Paracetamol/acetaminophen, one of the first choices for pain control in clinical dentistry, has been considered a weak anti-inflammatory drug, although supposedly capable of inhibiting COX-2 activity in inflammatory sites. OBJECTIVE: The purpose of the present study was to investigate whether paracetamol, ketorolac and etoricoxib can hinder alveolar bone formation, taking the filling of rat extraction socket with newly formed bone as experimental model. MATERIAL AND METHODS: The degree of new bone formation inside the alveolar socket was estimated two weeks after tooth extraction by a differential point-counting method, using an optical microscopy with a digital camera for image capture and histometry software. Differences between groups were analyzed by ANOVA after confirming a normal distribution of sample data. RESULTS AND CONCLUSIONS: Histometric results confirmed that none of the tested drugs had a detrimental effect in the volume fraction of bone trabeculae formed inside the alveolar socket.

Effects of sildenafil on autonomic nervous function during sleep in obstructive sleep apnea

OBJECTIVE: To evaluate the effects of sildenafil on the autonomic nervous system in patients with severe obstructive sleep apnea. METHODS: Thirteen male patients with severe obstructive sleep apnea (mean age 43±10 years with a mean body mass index of 26.7±1.9 kg/m²) received a single 50-mg dose of sildenafil or a placebo at bedtime. All-night polysomnography and heart rate variability were recorded. Frequency domain analysis of heart rate variability was performed for the central five-minute sample of the longest uninterrupted interval of slow wave and rapid eye movement sleep, as well as for one-minute samples during apnea and during slow wave and rapid eye movement sleep after resumption of respiration. RESULTS: Compared to the placebo, sildenafil was associated with an increase in the normalized high-frequency (HFnu) components and a decrease in the low/high-frequency components of the heart rate variability ratio (LF/HF) in slow wave sleep (p<0.01 for both). Differences in heart rate variability parameters between one-minute post-apnea and apnea samples (Δ= difference between resumption of respiration and apnea) were assessed. A trend toward a decreasing magnitude of ΔLF activity was observed during rapid eye movement sleep with sildenafil in comparison to placebo (p=0.046). Additionally, Δ LF/HF in SWS and rapid eye movement sleep was correlated with mean desaturation (sR= -0.72 and -0.51, respectively, p= 0.01 for both), and Δ HFnu in rapid eye movement sleep was correlated with mean desaturation (sR= 0.66, p= 0.02) and the desaturation index (sR= 0.58, p = 0.047). CONCLUSIONS: The decrease in arousal response to apnea/hypopnea events along with the increase in HFnu components and decrease in LH/HF components of the heart rate variability ratio during slow wave sleep suggest that, in addition to worsening sleep apnea, sildenafil has potentially immediate cardiac effects in patients with severe obstructive sleep apnea.

Central retinal vein occlusion in a patient after being commenced on sildenafil citrate for pulmonary arterial hypertension.

A 75-year-old female was commenced on sildenafil for the treatment of pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD). She reported blurring of vision within 72 hours after starting treatment and was found to have a central retinal vein occlusion (CRVO). Such an occurrence is the second case reported to date, and we review the possible mechanisms and literature on the subject.

Cardiovascular and hematologic effects produced by chronic treatment with etoricoxib in normotensive rats / Efeitos cardiovasculares e hematológicos produzidos pelo tratamento crônico com etoricoxib em ratos normotensos

PURPOSE: Evaluate the cardiovascular and hematological effects produced by chronic treatment with two dosis of etoricoxib in Wistar normotensive rats. METHODS: Thirty rats have been used and divided into one control group and two etoricoxib (10mg/kg and 30mg/kg) treatments groups for 60 days. The mean arterial pressure (MAP) was taken during the whole experimental period and at the end of this period, under anesthesia blood samples were taken, and further the withdrawn of the aorta, heart, brain, liver, and kidneys for the anatomopathologic study. RESULTS: The treatment with etoricoxib (30mg/Kg) produced a significant increase of the MAP from the 28th day of the experiment and from the platelets when compared to the control group and to the group treated with 10mg/Kg, besides producing a highly significant difference in hematocrit and in the red blood cells in relation to the control group. On the other hand the treatment with etoricoxib has not caused histopathological changes when compared to the control. CONCLUSION: These data show that the chronic treatment with etoricoxib leads to increase of the MAP, and to important hematological changes which seem to be associated to the hemoconcentration although not producing anatomopathological significant changes.

OBJETIVO: Avaliar os efeitos cardiovasculares e hematológicos produzidos pelo tratamento crônico com duas doses de etoricoxib em ratos Wistar normotensos. MÉTODOS: Foram utilizados 30 ratos divididos em um grupo controle e dois grupos tratamentos (10mg/kg e 30mg/kg) de etoricoxib por 60 dias. A pressão arterial média (PAM) dos animais foi aferida durante todo o período experimental e, ao final deste, sob anestesia, foram coletadas amostras de sangue, além da retirada da aorta, coração, cérebro, fígado e rins para estudo anatomopatológico. RESULTADOS: O tratamento com etoricoxib (30mg/Kg) produziu aumento significativo da PAM a partir do 28° dia do experimento e das plaquetas quando comparado ao grupo controle e ao grupo tratado com etoricoxib 10 mg/Kg, além de produzir diferença altamente significativa no hematócrito e nas hemácias em relação ao grupo controle. Por outro lado, o tratamento com etoricoxib, não produziu alterações histopatológicas quando comparado ao controle. CONCLUSÃO: Estes dados indicam que o tratamento crônico com etoricoxib produz aumento da PAM, além de importantes alterações hematológicas que parecem estar associadas à hemoconcentração, porém sem produzir alterações anatomopatológicas significativas.

Recurrent haemoptysis following sildenafil administration.

Sildenafil is widely used in the treatment of male erectile disorder and is generally well-tolerated. Its adverse effects are reported to be mild and include flushing, headache, dyspepsia and visual disturbances. We document a case of recurrent haemoptysis observed soon after self administration of sildenafil in a 38-year-old male with no other causative factors. The episodes of haemoptysis stopped following stoppage of sildenafil.

Subarachnoid haemorrhage: possibly caused by the illegitimate use of sildenafil citrate.

Sildenafil (Viagra) has been developed as a drug to treat male impotence. It has also been used to reduce symptoms (e.g. improved exercise capacity) in patients with pulmonary arterial hypertension. A case of subarachnoid haemorrhage (SAH) following the illicit use of sildenafil is reported.

Sildenafil citrate and Torsade de pointes

Sildenafil citrate is a drug used in the treatment of erectile dysfunction. It is an inhibitor of the enzyme phosphordiesterase-5; it slows down the breakdown of c-GMP and nitrous oxide. The cardiac effects associated with Sildenafil citrate have been extensively studied in medical literature, especially its potent vasodilatory effect when combined with nitrate-based medications, producing intractable hypotension, but a lesser known and potentially lethal side effect is prolonged cardiac repolarization when used at dosage greater than recommended, leading to QT prolongation that could theoretically lead to dangerous cardiac dysrrhythmias and sudden death in men with coronary artery disease. The authors present the case of a 49-year-old hypertensive Hispanic man who arrived to our emergency department with the chief complaint of acute epigastric pain for 3 hours of evolution after ingestion of Sildenafil citrate 50 milligrams (mg). The patient was found to have an acute ST elevation inferior myocardial infarction (STEMI). Shortly after diagnosis the patient developed a polymorphic ventricular tachycardia (Torsade de pointes) before thrombolytic administration. We present this case followed by a brief discussion, to heighten awareness of the possible association of acute inferior STEMI and the development of Torsade de Pointes after the use of Sildenafil citrate.

Efficacy and safety of sildenafil in Asian males with erectile dysfunction and cardiovascular risk.

OBJECTIVE: Assess the effectiveness of sildenafil in Asian males with erectile dysfunction (ED) and one or more of the co-morbidities, mild-to-moderate hypertension, dyslipidemia, and diabetes. MATERIAL AND METHOD: A six-week, double-blind, randomized, placebo-controlled, multicenter study was carried out in Thailand, Malaysia and Singapore. One hundred and fifty five male subjects were randomized (2:1) to sildenafil (n = 104) or placebo (n = 51). Sildenafil was started at 50 mg and increased (100 mg) or decreased (25 mg) at week 2 if necessary. RESULTS: On the primary efficacy endpoint, sildenafil-treated subjects had significantly better scores on the International Index of Erectile Function (IIEF) questions 3 and 4 than placebo (p < 0.001, both questions). When accumulated into IIEF domains, all five domains were significant in favor of sildenafil. In addition, sildenafil-treated subjects were more satisfied with treatment and had a higher intercourse success rate. The majority of adverse events were mild in severity; the most commonly reported treatment-related events were dizziness (7.7%) and tinnitus (2.9%). CONCLUSION: Sildenafil (25, 50, and 100 mg) was found to be an effective, safe, and well-tolerated treatment for ED in the present study population of Thai, Malaysian, and Singaporean males who also had increased cardiovascular risk

Inhaled iloprost for severe persistent pulmonary hypertension of the newborn.

The authors report one case of persistent pulmonary hypertension that had hypoxia although receiving treatment with high frequency oscillation, inotropic drugs, blood transfusion, and oral sildenafil for pulmonary vasodilatation. The patient developed hypotension after two doses of oral sildenafil and no response to high dose of inotropic drugs. So aerosolized iloprost was given via endotracheal tube and oxygen saturation improved within 10 minutes. Oxygen was weaned at 36 hours after treatment with this drug and no any side effect was found.