Current Drug Safety - Volume 16, Issue 3, 2021

Background: Clopidogrel has been commonly prescribed as a selective P2Y12 receptor antagonist to reduce heart attack and stroke risk. Nearly 10% of absorbed clopidogrel is metabolized to active forms by cytochrome P450 (CYP) enzymes in the liver and 90% to inactive clopidogrel carboxylate by esterases. Objective: Since different forms of clopidogrel have cytotoxic potential, our aim was to determine the effect of 7.5, 40, and 75μM clopidogrel over DNA damage in adipocytes and hepatocytes. Methods: In the present study, DNA damage was investigated by Comet analysis using 3T3-L1 adipocytes and Alpha Mouse 12 (AML-12) hepatocytes. Results: DNA fragmentation was found to be increased as a response to 7.5 μM, 40 μM, and 75 μM clopidogrel treatment compared to non-treated control groups in AML-12 hepatocytes (p<0.01, p<0.001, p<0.01 respectively) and 3T3-L1 adipocytes (p<0.001, p<0.001 and p<0.001respectively). DNA damage levels as a response to clopidogrel treatment were found to be higher in 3T3-L1 adipocytes than AML-12 hepatocytes. Also, DNA damage levels in adipocytes and hepatocytes were found to increase dose-dependently for 7.5 and 40 μM clopidogrel, whereas decreased as a response to 75 μM. Conclusion: According to our results, clopidogrel results in more DNA damage in adipocytes than in hepatocytes. The molecular mechanism of clopidogrel genotoxicity needs to be further investigated especially in adipose tissue.

Background: Colistin utilization has gradually increased worldwide with the rising of multidrug-resistant (MDR) gram-negative bacilli despite its nephrotoxicity. Lipid emulsion (LE) is widely used for the toxic overdose treatment of various drugs. Objective: The aim of the present study is to evaluate the effect of lipid emulsion on the improvement of renal damage in colistin-induced nephrotoxicity with an experimental Sprague Dawley rat model. Methods: Twenty-four male Sprague Dawley rats were initially assigned to 2 random groups. Sixteen rats were given a single dose of 20 mg/kg colistin, and eight rats received no medication (control group). Sixteen rats that were administered colistin were sub-divided into 2 groups. Group 1/LE rats (n = 8) were given 20 ml/kg solution of lipid emulsion, and group 2/S rats (n = 8) were given 20 ml/kg/day (i.p.) of 0.9% NaCl saline; both were administered for 10 days. Then tubular injury was evaluated histopathologically. Serum levels of blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), and creatinine were measured. Besides, malondialdehyde (MDA) levels were determined in tissue samples for the assessment of lipid peroxidation. Results: The mean percent of tubular epithelial cell injury and tubular dilatation was found significantly higher in group 2/S than in control and group 1/LE (p < 0.0001 and < 0.001; respectively). KIM-1 and MDA levels were also statistically higher in group 2/S than in control and group 1/LE. (p < 0.0001 and < 0.0001; respectively). Additionally, serum BUN and creatinine levels of group 2/S were significantly greater than control and group 1/LE (p < 0.0001 and < 0.0001; respectively). Conclusion: In this present study, we determined that colistin-induced proximal tubular damage was decreased histopathologically and serologically by the effect of lipid emulsion. Thus, our findings may guide future studies on the clinical use of colistin, particularly in MDR positive intensive care infections.

Background: Drugs with anticholinergic properties are known to be associated with deleterious effects on cognition in older adults. There is a paucity of literature in this aspect in older adults with psychiatric disorders. Objective: To examine the anticholinergic cognitive burden and its predictors in hospitalised older adults having psychiatric disorders. Methods: Case records of older adults who sought in-patient care under the Geriatric Psychiatry Unit from January 2019 to June 2019 were reviewed. The anticholinergic burden was assessed with Anticholinergic Cognitive Burden (ACB) scale updated version, 2012. Results: Sample included 129 older adults with an almost equal number of males (53.48%) and females (46.52%) having a mean age of 67.84 (SD = 6.96) years. The diagnostic spectrum included depression (34.89%), dementia (31.01%), mania (10.85%), psychosis (13.95%), delirium (6.20%), and others (3.1%). 60.47% of the patients had more than one medical illness. 48.84% of the older adults had clinically relevant anticholinergic cognitive burden (ACB score ≥ 3). Use of 3 or more psychotropic drugs (OR = 4.88), diagnosis of psychosis/mania (OR = 7.62) and dementia/ delirium (neurocognitive disorders group) (OR = 5.17) increased the risk of ACB score ≥ 3. Conclusion: Nearly half of the older adults in the psychiatry in-patient setting had a clinically relevant anticholinergic burden, which was associated with higher use of psychotropics. Our study highlights the importance of monitoringanticholinergic effects of psychotropics in older adults.

Background: Gallstone disease (GSD) is one of the most common gastroenterological disorders. It is known that drospirenone causes small increased risk of gallbladder diseases. However, the risk may vary between different adverse drug reaction databases. Objective: The purpose of this studty is to examine the safety and risk association between hormonal contraceptive drospirenone and gallbladder diseases using adverse drug reaction database of USFDA’s Federal Adverse Events Reporting System (FAERS), Europe’s Eudravigilance (EV) and Canada’s Canada Vigilance Adverse Reaction Online Database (CVARD). Methods: Individual Case Safety Reports of patients till October 2019 were downloaded from the Federal Adverse Event Reporting System, Eudravigilance, and Canadian database. These reports contained information on adverse events associated with all other drugs inclusive of drospirenone. The disproportionality method of data mining was used to calculate the risk association. Results: The lower limit of 95% CI of PRR was 3.27, 3.47 and 3.76, PRR was 33.08, 41.35 and 115.42, ROR was 37.20, 44.61 and 127.19, Chi-square value was 126572.89, 110392.95 and 362.46, and IC-2SD value was 0.16, 0.17, and 1.21 for FAERS, EU, and CVARD respectively indicating a week signal. Also, all the calculated parameters were above the threshold value. Conclusion: From our study, it was clear that the risk between drospirenone and gallbladder diseases was very low among three databases. There was no harm in prescribing this drug for a contraceptive action.

Background: Several studies have been published which stated that there is some connection between severe psychiatric disorders and contraceptive drug “desogestrel”. However, nothing in the summary of product characteristics (SmPC) or patient information leaflets of desogestrel about anxiety, more severe anxiety leading to panic attacks, or about risks of severe depression leading to suicidal thoughts or suicide attempts. Objective: To examine the safety and risk association between hormonal contraceptive desogestrel among women with psychiatric disorders using adverse drug reaction database of FDA Adverse Events Reporting System (FAERS) and EudraVigilance (EV). Methods: Individual case safety reports (ICSRs) of only female patients from Jan 1999 to Nov 2019 and Jan 2004 to Nov 2019 were downloaded from FAERS and EV database, respectively. Reports of drug desogestrel, dienogest, norgestimate, cyproterone acetate and drospirenone were downloaded. Disproportionality method of data mining was used to calculate the risk association. Results and Discussion: The lower limit of 95% CI of PRR is -0.28 and 2.02, PRR is 1.08 and 9.18, ROR is 1.09 (95%CI: 0.74, 1.59) and 9.26 (95% CI: 7.21, 11.89), Chi square value is 1.21 and 433.68, and IC-2SD is -0.27 and 2.60, respectively for data obtained from FAERS and EV. Conclusion: From this study, we conclude that there is no new emerging signal for the drug-event pair studied. Further study and continuous monitoring are required in future to know more about this drug-event pair association, as severe psychiatric disorders are not yet mentioned or included in SmPC and patient leaflet of desogestrel.

Background: With the recent widespread use of over-the-counter drugs, there has been a noticeable increase in the occurrence of gastrointestinal discomfort and peptic ulcer disease. However, peptic ulcer is a highly complex disorder resulting from an imbalance between gastric destructive and protective factors. Objective: To identify the risk factors of peptic ulcer disease. Methods: This study was organized at Al-Basra teaching hospital and Al Sader teaching hospital in Basrah city, Iraq. Medical records and questionnaires were filled by patients undergoing diagnostic and therapeutic upper gastrointestinal endoscopies following their gastric discomfort complaints. Information related to patients, disease history, and medication history for six months prior to endoscopy procedures was collected. Results: A total of 476 patients were identified, including 246 (51.7%) patients with endoscopically diagnosed peptic ulcers and 230 (48.3%) patients without peptic ulcers. The population was predominately male and there were significant differences between age groups. Smoking correlated with high relative risk; however, alcohol drinking had no significant role as a causative factor. The most extensively used drugs by patients who complained of peptic ulcers include NSAIDs, iron supplements, corticosteroids, and anti-platelet agents. A small number of patients were treated for hypertension and diabetes, which were correlated with peptic ulcer risks. The presence of H-pylori infections was significantly associated with peptic ulcer diagnosis. Conclusion: The risk of peptic ulcer disease appeared to increase with chronic medication use and smoking, which aggravate the contributing risk by H-pylori infections.

Background: Quinacrine is an older antimalarial drug that remains in use for a variety of illnesses including treatment-resistant giardiasis. Case Presentation: We report a patient with no prior psychiatric history who developed mild, prodromal psychiatric symptoms when treated with quinacrine for treatment-resistant giardiasis. Symptoms resolved when the drug was stopped, recurred with greater severity (requiring involuntary psychiatric hospitalization) when restarted and promptly resolved again when the drug was finally stopped. Conclusion: Although quinacrine remains in use today, providers may be unaware of its potential for serious neuropsychiatric toxicity.

Background: Xylometazoline, a sympathomimetic agent, is considered safe in hypertensive patients as a relief measure for nasal congestion with intranasal application. Case Report: In the present case, a 58-year old male patient, having ischemic heart disease, controlled hypertension on telmisartan and bisoprolol, experienced hypertensive urgency in a span of two hours of intranasal administration of the paediatric formulation of xylometazoline. Conclusion: The interaction with bisoprolol should be kept in mind while using xylometazoline.

Background: A rare type of cutaneous adverse drug reaction (CADR), lichenoid drugeruption (LDE), can be associated with ethambutol. Case Report: A 60-year-old woman with spinal tuberculosis received multiple anti-TB medications and developed rashes after 3 months of the treatments. A skin biopsy from the posterior auricular area confirmed lichenoid dermatitis, and the Naranjo causality assessment indicated ethambutol as a probable cause of LDE in the patient. The rashes slowly improved after discontinuation of ethambutol. Unfortunately, the residual of brown hyperpigmentation on the body still persisted for over 16 months. Conclusion: The medications were reduced to isoniazid 300 mg/day and rifampicin 450 mg /day as planned for another 3 months. This case report points out the essentials of early recognition of ethambutol LDE by health care professionals.

Background: Ivermectin is widely used for the treatment of neglected tropical diseases associated with adverse maternal and fetal outcomes when the infection complicates the pregnancy. However, the United States FDA classification and current distribution protocols limit ivermectin treatment in pregnant women because antepartum safety has not been well-established. Objective: We conducted a scoping review to address the question of what is known from both human and vertebrate animal studies about the safety of systemic ivermectin exposure during pregnancy. Methods: We searched PubMed for adverse outcomes related to systemic ivermectin exposure in human and vertebrate animal pregnancies, including English-language primary articles from 1900 - 2019. Results: We identified 23 primary articles for evaluation, including 10 human studies and 13 vertebrate animal studies of interest. One prospective randomized, controlled trial investigating the safety of systemic ivermectin exposure during pregnancy and four retrospective human studies did not identify a significant association with adverse birth outcome metrics. Out of the three human case reports, two reported uncomplicated prenatal courses and one reported stillbirth and maternal death. A retrospective cross-sectional study concluded a positive association between onchocerciasis and spontaneous abortion, mitigated by ivermectin mass drug administration. While adverse pregnancy outcomes were observed at high doses in mice, rats, and rabbits, there was overall a lack of evidence to support concerns that therapeutic doses of ivermectin (0.2 mg/kg) cause adverse pregnancy outcomes. Conclusion: Further research is warranted to address safety concerns regarding the use of ivermectin in pregnant women in treating and preventing neglected helminth infections that threaten maternal-child health.

Background: Minocycline is a tetracycline antibiotic that is widely used to treat infections and is a first-line oral antibiotic in the treatment of moderate to severe inflammatory acne. Although it has high efficacy, several adverse reactions, including life-threatening ones, have been reported in association with its use. Objective: To identify all the potential adverse reactions due to minocycline and analyze them in terms of the number of cases reported so far, salient features, severity and clinical outcome. Methods: Comprehensive PubMed search of English and non-English literature for case reports of adverse reactions to minocycline was conducted. Results: A total of 550 cases were identified from over 200 publications. The major reported adverse events caused by minocycline are drug reaction with eosinophilia and systemic symptoms syndrome, autoimmune syndromes like hepatitis, lupus and vasculitis, acute eosinophilic pneumonia, pseudotumor cerebri, hyperpigmentation, serum sickness-like reaction, Sweet’s syndrome and drug fever. Several other reactions involving multiple organ systems have also been reported. These show an overlap of clinical features and may be associated with multiple events causing considerable morbidity. Eight of these cases resulted in the death of the patients. Conclusion: In view of the evident potential of minocycline to cause long-lasting and severe adverse effects, significant morbidity and even mortality, it should be prescribed with caution in the first-line treatment for moderate to severe acne.

Objective: This systematic review aims to investigate the role and responsibilities of pharmacists in the prevention of medication errors. The study also aims to evaluate pharmacist-centered strategies that have an impact on medication error reduction and prevention. Methods: A search was conducted through the following databases PubMed Central, Scopus, Trip, Prospero, Medline and Google Scholar using terms related to “medication errors prevention” or “pharmacist-related errors”. Other search terms included “pharmacist(s)”, “prevention”, “medication error(s)”, “dispensing error(s)”, “drug incidence(s)”, “medication malpractice(s)”. Included studies were prospective and retrospective cohort, case-control and cross-sectional full-text studies published in the last 10 years (2010-2020). The review team screened the articles for inclusion criteria and evaluated the quality of the articles. The PRISMA guidelines were used to report the selected articles and screening process. Then, the articles were sent to a third independent reviewer for the quality assessment using the STROBE Checklist. Results: A clinical pharmacist’s duties are to supervise the medication treatment of admitted patients and to notify the healthcare team when a discrepancy is found. A total of seven reviewed studies highlighted the importance and positive impact of increasing the number of clinical pharmacist’s interventions. Literature showed that an average of 64.9% of medication discrepancies happen during patient discharge, highlighting the necessity of a clinical pharmacist intervention at that stage. The systematic review focused on the significant impact of clinical pharmacists’ role in preventing errors (studies reported=5); encouraging pharmacist-led education to increase medication error awareness (studies reported =5), incorporating better and innovative pharmacy-related work approaches (studies reported =4); and implementing appropriate and secured policies for medication error reporting (studies reported =1). The screened literature highlighted the significant reduction in the number of medication errors and an increase in medication error identification and awareness. These findings suggest the crucial role of a pharmacist in healthcare policies for the prevention of medication errors and patient safety. Conclusion: This systematic review suggests multiple pharmacist-centered strategies that have been implemented in several studies showing the positive impact on the reduction and prevention of medication errors commenced by not only the pharmacist but the rest of the healthcare team.