Quantitative Structure-Activity Relationship (QSAR) Model for the Severity Prediction of Drug-Induced Rhabdomyolysis by Using Random Forest.

Drug-induced rhabdomyolysis (DIR) is a rare and potentially life-threatening muscle injury that is characterized by low incidence and high risk. To our best knowledge, the performance of the current predictive models for the early detection of DIR is suboptimal because of the scarcity and dispersion of DIR cases. Therefore, on the basis of the curated drug information from the Drug-Induced Rhabdomyolysis Atlas (DIRA) database, we proposed a random forest (RF) model to predict the DIR severity of the marketed drugs. Compared with the state-of-art methods, our proposed model outperformed extreme gradient boosting, support vector machine, and logistic regression in distinguishing the Most-DIR concern drugs from the No-DIR concern drugs (Matthews correlation coefficient (MCC) and recall rate of our model were 0.46 and 0.81, respectively). Our model was subsequently applied to predicting the potentially serious DIR for 1402 drugs, which were reported to cause DIR by the postmarketing DIR surveillance data in the FDA Spontaneous Adverse Events Reporting System (FAERS). As a result, 62.7% (94) of drugs ranked in the top 150 drugs with the Most-DIR concerns in FAERS can be identified by our model. The top four drugs (odds ratio >30) including acepromazine, rapacuronium, oxyphenbutazone, and naringenin were correctly predicted by our model. In conclusion, the RF model can well predict the Most-DIR concern drug only based on the chemical structure information and can be a facilitated tool for early DIR detection.

Drug-induced parotitis.

Drug-induced parotitis is a relatively uncommon adverse drug reaction. Most of the data on drug-induced parotitis consist of isolated case reports with few attempts at rechallenge to confirm the aetiology. Phenylbutazone and oxyphenbutazone have a significant number of reports suggesting that these drugs may be implicated in causing parotitis. Antipsychotics, particularly thioridazine, have been associated with parotitis. Most of these reports relate the anticholinergic oral drying as a predisposing factor in the development of a parotid gland infection. There is inadequate literature on the histamine (H2) receptor blockers, interferon-alpha, doxycycline, trimipramine, nifedipine, methyldopa, nitrofurantoin, nicardipine, isoproterenol or ritodrine to link them as aetiological agents in the development of parotitis.

Effects of commonly used NSAID's on gastric mucosa. A clinico-endoscopic and histopathological study.

Non steroidal anti-inflammatory drugs (NSAID's) are one of the most commonly used agents in clinical practice today. All these drugs are known to produce gastro-intestinal lesions. In the present study we found that aspirin, indomethacin and phenylbutazone caused gastric mucosal damage in 90.9%, 100%, respectively while ibuprofen and paracetamol caused gastric mucosal damage in 33.3% and 37.5% respectively. Thus latter two drugs were safer NSAID's. Further more we have demonstrated that endoscopic monitoring of the patients on NSAID's is a sensitive method of early detection of gastric mucosal damage. This monitoring may be particularly valuable in high risk subjects on NSAID's.

A new approach to encapsulating nonsteroidal anti-inflammatory drugs. IV. Effect of cellulose derivatives with different functional groups on the bioavailability and gastric ulcerogenic activity of acidic as well as basic nonsteroidal anti-inflammatory drugs.

The bioavailability and gastric ulcerogenic activity of oxyphenbutazone and glafenine (acidic and basic nonsteroidal anti-inflammatory drugs), coated with different cellulose derivatives were assessed in albino rats. The cellulose derivatives chosen have different functional groups, acidic (carboxymethyl cellulose), basic (chitosan) and neutral (hydroxypropylmethyl cellulose). The bioavailability was dependent on the drug and polymers. Generally, all the cellulose derivatives chosen decreased the gastric ulcerogenic activity of the drugs studied.

[Toxic epidermal necrolysis in children (Lyell's syndrome). Apropos of 18 cases]. / Nécrolyse épidermique toxique de l'enfant (syndrome de Lyell). A propos de 18 cas.

The authors report 18 children with toxic epidermal necrolysis (T.E.N.). The clinical and laboratory signs, the development of complications and sequelae and the drugs presumed to be responsible are compared with those of T.E.N. in adults. The onset was generally marked by a influenza-like state with development of mucosal signs between the first and the seventh days. The lips and buccal cavity were involved in 16 cases and the eyelids and conjunctiva were involved in 15 cases. Epidermal loss occurred after a variable interval of between one and eight days after the appearance of the erythema. The severity of the epidermal loss, expressed as a percentage of the body surface area, was a poor prognostic factor. Hypoproteinaemia was the most frequently observed laboratory abnormality. The complications were infectious and the 2 deaths in this series were due to septicaemia. Ocular complications were also observed: keratitis, responsible for sequelae such as distichiasis, conjunctival adhesions, sicca syndrome. As in adults, these children were frequently taking multiple drugs. Among the drugs prescribed during the classical interval of imputability, two drugs were particularity noted: phenobarbital and oxyphenbutazone. Treatment should only be undertaken in a specialized unit and is based on the principles of intensive care of burns patients: control of hypovolemia and infection. Ocular sequelae should be prevented by local treatments several times a day.

Reaçöes hematológicas adversas a drogas e produtos quimícos / Hematological adverse reaction of drugs and chemical products

O autor apresenta um resumo das mais importantes reaçöes hematológicas adversas secundárias a produtos químicos e/ou drogas de uso clínico. Destaca a conduta médica de prevençäo e tratamento nestes casos. Além disso, o autor apresenta um breve sumário da experiência da disciplina de Hematologia Clínica da FCM - UNICAMP em Aplasia Medular, com destaque às causas prováveis mais importantes