SciCombinator

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Concept: Adverse drug reaction

404

Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-RIs). Clinical trial reports and the manufacturers' full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure.

Concepts: Clinical trial, Effectiveness, ClinicalTrials.gov, Pharmaceutical industry, Adverse drug reaction, Erectile dysfunction, Exposure

193

Since the first ADA working group report on the recommendations for management of diabetes during Ramadan in 2005 and our update in 2010, we received many inquiries asking for regular updates on information regarding education, nutritional habits and new oral and injectable agents that may be useful for the management of patients with diabetes during Ramadan. Patients can be stratified into their risk of hypoglycemia and/or complications prior to the start of the fasting period of Ramadan. Those at high risk of hypoglycemia and with multiple diabetic complications should be advised against prolonged fasting. Even in the lower hypoglycemia risk group, adverse effects may still occur. In order to minimize adverse side effects during fasting in patients with diabetes and improve or maintain glucose control, education and discussion of glucose monitoring and treatment regimens should occur several weeks prior to Ramadan. Agents such as metformin, thiazolidinediones and dipeptidyl peptidase-4 inhibitors appear to be safe and do not need dose adjustment. Most sulfonylureas may not be used safely during Ramadan except with extreme caution; besides, older agents, such as chlorpropamide or glyburide, should not be used. Reduction of the dosage of sulfonylurea is needed depending on the degree of control prior to fasting. Misconceptions and local habits should be addressed and dealt with in any educational intervention and therapeutic planning with patients with diabetes. In this regard, efforts are still needed for controlled prospective studies in the field of efficacy and safety of the different interventions during the Ramadan Fast.

Concepts: Therapeutic effect, Nutrition, Diabetes mellitus, Hypoglycemia, Sulfonylurea, Metformin, Adverse drug reaction, Fasting

192

Discovering the unintended ‘off-targets’ that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended ‘side-effect’ targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1 nM to 30 μM. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery.

Concepts: Scientific method, Pharmacology, Blood, Chemotherapy, Platelet, Aspirin, Adverse drug reaction, Iatrogenesis

180

Acetaminophen (paracetamol) is one of the most common medications used for management of pain in the world. There is lack of consensus about the mechanism of action, and concern about the possibility of adverse effects on reproductive health.

Concepts: Health, Influenza, Cytochrome P450, Paracetamol, Adverse drug reaction, World, Adverse effect

179

Adverse drug reactions and interactions are among the major causes of death in the United States. Antidepressants have been reported as causing suicide and homicide and share the class attribute of frequently producing akathisia, a state of severe restlessness associated with thoughts of death and violence. Medical examiners can now identify some pharmacogenetic interactions that cause drugs, deemed safe for most, to be lethal to others. Such deaths do not yet include medication-induced, akathisia-related suicides and homicides. An extrapyramidal side effect, akathisia is a manifestation of drug toxicity whose causes lie, inter alia, in drugs, doses, and co-prescribed medications that inhibit and compete for metabolizing enzymes, which may themselves be defective. In this paper, we report our investigation into adverse drug reactions/interactions in three persons who committed homicide, two also intending suicide, while on antidepressants prescribed for stressful life events. Their histories of medication use, adverse reactions and reasons for changes in medications are presented. DNA samples were screened for variants in the cytochrome P450 gene family; that produce drug metabolizing enzymes. All three cases exhibit genotype-based diminished metabolic capability that, in combination with their enzyme inhibiting/competing medications, decreased metabolism further and are the likely cause of these catastrophic events.

Concepts: Protein, Pharmacology, Metabolism, Cytochrome P450, Enzyme inhibitor, Adverse drug reaction, Pharmaceutical drug, Suicide

167

INTRODUCTION: Linezolid-induced black hairy tongue has been rarely reported. The purpose of this paper is to report a case of linezolid-induced black hairy tongue and review the literature. CASE PRESENTATION: A 56-year-old Caucasian man was admitted with community-acquired pneumonia that failed to respond to levofloxacin 750mg daily. He was started on linezolid and meropenem and was subsequently discharged home on oral linezolid 600mg every 12 hours and intravenous ertapenem 1g daily. On a follow-up clinic visit, day 14 of linezolid therapy, he complained of dysgeusia and his tongue examination was consistent with black hairy tongue. After he finished his antibiotic course, his complaints resolved with regular tongue brushing. CONCLUSION: Black hairy tongue is characterized by abnormal hypertrophy and elongation of filiform papillae. Five reported cases of linezolid-induced black hairy tongue were identified in a MEDLINE search (from January 2000 to June 2012). The Naranjo Probability Scale revealed a probable adverse drug reaction of linezolid-induced black hairy tongue. Potential contributing factors included other antibiotics, drug–drug interaction and poor oral hygiene. Health care professionals should be aware of the possibility of linezolid-induced black hairy tongue. Thorough history for other possible contributing factors should be obtained. Patients on linezolid should be counseled to perform good oral hygiene.

Concepts: Antibiotic resistance, Probability, Adverse drug reaction, Oral hygiene, Taste bud, Papilla, Black hairy tongue

163

The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients' experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance.

Concepts: Pharmacology, Adverse drug reaction, Idiosyncratic drug reaction, Benzodiazepine, Pharmacovigilance, Drug safety

163

Drug molecules with lack of specificity and solubility lead patients to take high doses of the drug to achieve sufficient therapeutic effects. This is a leading cause of adverse drug reactions, particularly for drugs with narrow therapeutic window or cytotoxic chemotherapeutics. To address these problems, there are various functional biocompatible drug carriers available in the market, which can deliver therapeutic agents to the target site in a controlled manner. Among the carriers developed thus far, mesoporous materials emerged as a promising candidate that can deliver a variety of drug molecules in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles are widely used as a delivery reagent because silica possesses favourable chemical properties, thermal stability and biocompatibility. Currently, sol-gel-derived mesoporous silica nanoparticles in soft conditions are of main interest due to simplicity in production and modification and the capacity to maintain function of bioactive agents. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release. The properties of mesopores, including pore size and porosity as well as the surface properties, can be altered depending on additives used to fabricate mesoporous silica nanoparticles. Active surface enables functionalisation to modify surface properties and link therapeutic molecules. The tuneable mesopore structure and modifiable surface of mesoporous silica nanoparticle allow incorporation of various classes of drug molecules and controlled delivery to the target sites. This review aims to present the state of knowledge of currently available drug delivery system and identify properties of an ideal drug carrier for specific application, focusing on mesoporous silica nanoparticles.

Concepts: Pharmacology, Nanoparticle, Adverse drug reaction, Materials, Mesoporous material, Mesoporous silica, Silicon compounds, Drug carrier

161

To evaluate the risk of severe cutaneous adverse drug reactions (SCAR) after exposure to multi-indication antiepileptic drugs for in Korean elderly patients.

Concepts: Pharmacology, Illness, Epilepsy, Adverse drug reaction, Anticonvulsant, Benzodiazepine, Carbamazepine, Primidone

160

Automatic monitoring of Adverse Drug Reactions (ADRs), defined as adverse patient outcomes caused by medications, is a challenging research problem that is currently receiving significant attention from the medical informatics community. In recent years, user-posted data on social media, primarily due to its sheer volume, has become a useful resource for ADR monitoring. Research using social media data has progressed using various data sources and techniques, making it difficult to compare distinct systems and their performances. In this paper, we perform a methodical review to characterize the different approaches to ADR detection/extraction from social media, and their applicability to pharmacovigilance. In addition, we present a potential systematic pathway to ADR monitoring from social media.

Concepts: Pharmacology, Medicine, Performance, Adverse drug reaction, Pharmacy, Pharmacovigilance, American Depositary Receipt, Medical informatics