Drug-induced Stevens-Johnson syndrome in Indian population: A multicentric retrospective analysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening hypersensitivity reactions mainly caused by drugs. Data on incubation period, hospital stay, and outcome for HIV-positive patients are sparse. Role of corticosteroids in their management is still controversial. METHODS: Indoor cases of SJS, SJS-TEN overlap, and TEN were analyzed for causative drugs, incubation period, a severity-of-illness score for toxic epidermal necrolysis (SCORTEN) score, HIV status, treatment, and outcome. Comparison of parameters between HIV and non-HIV cases was done. Utilization pattern of corticosteroids and their role in outcome were evaluated. RESULTS: Four SJS, 15 SJS-TEN overlap, and 21 TEN cases were evaluated. Antimicrobials (27.1%), antiviral (23%), antiseizure drugs (8.4%), and analgesics (8.4%) were commonly associated drugs. Among 12 (30%) HIV-reactive cases, nevirapine (97.6%) and cotrimoxazole (41.6%) were common causative drugs. Males (75%) were affected more than females (25%) among HIV-positive individuals. Incubation period was significantly higher in HIV-reactive patients. Total 30 (75%) patients were treated with corticosteroids. Dexamethasone (90%) and prednisolone (26.6%) were most commonly used. No significant difference was found among cases treated with or without corticosteroids. CONCLUSIONS: Antimicrobial drugs are common to cause SJS/TEN. Among HIV-reactive patients, male have more risk, incubation period is more and severity of reaction is less. Effectiveness of corticosteroids for treatment of SJS/TEN is inconclusive.

Cardiovascular abnormalities with single dose of tapentadol.

This case represents the development of dizziness, palpitation, tightness in chest, flushing, and tremor on consumption of a single dose of tapentadol (100 mg) for acute lower back pain. The patient was admitted in the intensive cardiac care unit for continuous monitoring. At admission, electrocardiogram showed tachycardia (140/min) along with ST segment elevation in second chest lead (V2). The patient was monitored and advised not to take further doses of tapentadol. He was discharged after 36 hours of admission. Tapentadol should be used cautiously in patients with cardiovascular diseases and receiving sympathomimetic drugs.

Effect of Zidovudine and its interaction with rocuronium on neuromuscular transmission.

Neuromuscular weakness is often found in patients receiving zidovudine therapy due to mitochondrial damage. Effect of zidovudine was evaluated in indirectly and directly stimulated isolated rat phrenic nerve hemidiaphragm preparations, by cumulative dose response curve with square wave pulses, 0.5 ms duration of 2 Hz at every 10 s. To understand the observed effect of zidovudine, interaction studies were carried out with rocuronium. Dose response curve of rocuronium was compared in the absence and in the presence of 1.2 and 12 mmol/ml zidovudine. In another set of experiment, intact animals were treated with zidovudine 50 and 100 mg/kg for 15 days and phrenic nerve hemidiaphragm was obtained for in vitro experiment. Effect of zidovudine (30 mmol/ml) on twitch responses inhibited by dantrolene 50 µmol/ml, magnesium chloride 8 mmol/ml, rocuronium 10 µmol/ml, succinylcholine 25 µmol/ml and lignocaine 600 µmol/ml was studied. Zidovudine (3-30 mmol/ml) significantly augmented the twitch responses up to 80 and 40% in indirectly and directly stimulated preparations, respectively (P<0.05). Zidovudine did not show significant interaction with rocuronium in any group as per dose response curve and inhibitory concentration 5%, inhibitory concentration 50% and inhibitory concentration 95% of rocuronium. Zidovudine (30 mmol/ml) augmented the twitch responses inhibited by dantrolene, magnesium chloride and rocuronium. It reduced the time for complete block of succinylcholine (P<0.05). Zidovudine affects the neuromuscular transmission. No conclusive interaction between rocuronium and zidovudine was found.

Anti-urolithiatic effect of cow urine ark on ethylene glycol-induced renal calculi.

PURPOSE: To investigate the anti-urolithiatic effect of cow urine ark (medicinal distilled cow urine) on ethylene glycol (EG) induced renal calculi. MATERIALS AND METHODS: 36 male Wistar rats were randomly divided into 6 equal groups. Group I animals served as vehicle control and received distilled water for 28 days. Group II to VI animals received 1% v/v EG in distilled water for 28 days. Group II served as EG control. Group III and IV (preventive groups) received cow urine ark orally for 28 days in doses of 1 mL/kg and 2 mL/kg, respectively. Group V and VI (treatment groups) received 1 mL/kg and 2 mL/kg cow urine ark orally, respectively from 15th to 28th days. 24-hour urine samples were collected on day 0 and 28. Urine volume and oxalate levels were measured. On day 28, blood was collected for biochemical parameters. Animals were sacrificed and kidneys were harvested, weighed and histopathologically evaluated for calcium oxalate (CaOx) crystals. To calculate the percentage of inhibition of mineralization, simultaneous flow static in-vitro model was used. RESULTS: EG significantly increased urine oxalate, serum creatinine, blood urea level; kidney weight and CaOx deposits. Provision of cow urine ark resulted in significantly lower levels of urine oxalate, serum creatinine, blood urea and CaOx depositions as compared to Group II. (p value < 0.05) It also significantly restored kidney weight. (p value < 0.05) Cow urine ark inhibited 40% and 35% crystallization of CaOx and calcium phosphate, respectively. CONCLUSION: Cow urine ark is effective in prevention and treatment of EG induced urolithiasis in Wistar rats.

Anti-Urolithiatic Effect of Cow Urine Ark on Ethylene Glycol-Induced Renal Calculi

Purpose To investigate the anti-urolithiatic effect of cow urine ark (medicinal distilled cow urine) on ethylene glycol (EG) induced renal calculi. Materials and Methods 36 male Wistar rats were randomly divided into 6 equal groups. Group I animals served as vehicle control and received distilled water for 28 days. Group II to VI animals received 1% v/v EG in distilled water for 28 days. Group II served as EG control. Group III and IV (preventive groups) received cow urine ark orally for 28 days in doses of 1 mL/kg and 2 mL/kg, respectively. Group V and VI (treatment groups) received 1 mL/kg and 2 mL/kg cow urine ark orally, respectively from 15th to 28th days. 24-hour urine samples were collected on day 0 and 28. Urine volume and oxalate levels were measured. On day 28, blood was collected for biochemical parameters. Animals were sacrificed and kidneys were harvested, weighed and histopathologically evaluated for calcium oxalate (CaOx) crystals. To calculate the percentage of inhibition of mineralization, simultaneous flow static in-vitro model was used. Results EG significantly increased urine oxalate, serum creatinine, blood urea level; kidney weight and CaOx deposits. Provision of cow urine ark resulted in significantly lower levels of urine oxalate, serum creatinine, blood urea and CaOx depositions as compared to Group II. (p value < 0.05) It also significantly restored kidney weight. (p value < 0.05) Cow urine ark inhibited 40% and 35% crystallization of CaOx and calcium phosphate, respectively. Conclusion Cow urine ark is effective in prevention and treatment of EG induced urolithiasis in Wistar rats. .

Neuromuscular blocking effect of fluoxetine and its interaction with rocuronium.

As selective serotonin reuptake inhibitors have an inhibitory effect on nicotinic acetylcholine receptors, they may affect the neuromuscular transmission and interact with neuromuscular blockers. This study was designed to observe the effect of fluoxetine on neuromuscular transmission and its interaction with rocuronium using the rat phrenic nerve hemidiaphragm and rabbit head drop methods. Rat phrenic nerve hemidiaphragms were mounted and stimulated using a train of four pulses (TOF). The effect of fluoxetine was studied on both indirectly and directly stimulated basal twitch responses by plotting cumulative dose response curves (DRCs). DRCs of rocuronium were obtained in the absence, and presence of 5 µm and 20 µm fluoxetine to study its interaction. ED5 , ED50 and ED95 values of rocuronium DRCs in absence and presence of fluoxetine were calculated. Fluoxetine significantly inhibited twitch responses in both indirect and directly stimulated preparations. Fluoxetine (20 µm) caused an increase in the potency of rocuronium such that the ED50 and ED95 values of rocuronium DRCs were significantly decreased. Partially inhibited twitch responses by fluoxetine (100 µm) were not reversed by neostigmine (3.3 µm) or 3,4 diaminopyridine (0.25 µm). Rabbits were given fluoxetine 0.25 mg kg(-1) and 1 mg kg(-1) orally for 15 days, and on 15th day, rocuronium infusion was given, and time for head drop was recorded. The time of head drop was significantly reduced in fluoxetine pretreated as compared to control group. Fluoxetine blocks the neuromuscular transmission and increases the potency of rocuronium-induced neuromuscular block.

Drug-induced Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap: a multicentric retrospective study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare immune-mediated severe cutaneous adverse reactions with incidence rate of 0.05 to 2 persons per million populations per year. Drugs are the most commonly implicated in 95% of cases. AIMS: To audit the causative drugs, clinical outcome, and cost of management in SJS, TEN, and SJS-TEN overlap. SETTING AND DESIGN: Tertiary care hospitals-based multicentric retrospective study (case series). MATERIALS AND METHODS: Indoor case papers of SJS, TEN, and SJS-TEN overlap admitted between January 2006 and December 2009 in four tertiary care hospitals of Gujarat were scrutinized. Data were collected for demographic information, causative drugs, investigations, treatment given, duration of hospital stay, time interval between onset of symptoms and drug intake, clinical outcome, and complications. Data were analyzed to find out proportion of individual drugs responsible, major complications, and clinical outcome in SJS, TEN, and SJS-TEN overlap. Total cost of management was calculated by using cost of drugs, investigations, and consumables used during entire hospital stay. STATISTICAL ANALYSIS: One-way Analysis of Variance followed by Tukey-Kramer multiple comparison test was used for comparison of incubation period, duration of hospital stay, and cost of management. RESULTS: Antimicrobials (50%), nonsteroidal anti-inflammatory drugs (22.41%), and antiseizure drugs (18.96%) were the most commonly associated groups. Nevirapine (28.12%) was the most common drug. Antiseizure drugs were more often associated with serious form of adverse reaction (TEN: 81.8%) than other drugs. Duration of hospital stay (20.6 vs 9.7 days) and cost of management (7,910/- vs 2,460/-) were significantly higher in TEN than SJS (P=0.020 and P<0.001, respectively). Time duration between drug intake and onset of symptoms (17.7 vs 27.5 days) was nonsignificantly lower in TEN as compared with SJS. Secondary infection (28.12%) was the most common complication noted. Mortality rate was 15.6% among all cases; 9% in SJS and 26.7% in TEN. CONCLUSION: Antimicrobial drugs are the most commonly implicated drugs and cost of managing these adverse drug reactions is higher than other serious ADRs.