Multiple Adverse Drug Reactions Research Articles

Multivariate generalized mixed-effects models for screening multiple adverse drug reactions in spontaneous reporting systems.

Introduction: For assessing drug safety using spontaneous reporting system databases, quantitative measurements, such as proportional reporting rate (PRR) and reporting odds ratio (ROR), are widely employed to assess the relationship between a drug and a suspected adverse drug reaction (ADR). The databases contain numerous ADRs, and the quantitative measurements need to be calculated by performing the analysis multiple times for each ADR. We proposed a novel, simple, and easy-to-implement method to estimate the PRR and ROR of multiple ADRs in a single analysis using a generalized mixed-effects model for signal detection. Methods: The proposed method simultaneously analyzed the association between any drug and numerous ADRs, as well as estimated the PRR and ROR for a specific combination of drugs and suspected ADRs. Furthermore, the proposed method was applied to detect drug-drug interactions associated with the concurrent use of two or more drugs. Results and discussion: In our simulation studies, the false-positive rate and sensitivity of the proposed method were similar to those of the traditional PRR and ROR. The proposed method detected known ADRs when applied to the Food and Drug Administration Adverse Event Reporting System database. As an important advantage, the proposed method allowed the simultaneous evaluation of several ADRs using multiple drugs.

Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients

Aripiprazole is recommended for routine use in schizophrenia patients. However, the biological mechanism for the adverse drug reactions (ADRs) among schizophrenia patients with the antipsychotic drug aripiprazole is far from clear. To explore the potential genetic factors that may cause movement-related adverse antipsychotic effects in patients, we conducted an association analysis between movement-related ADRs and SNPs in schizophrenia patients receiving aripiprazole monotherapy. In this study, multiple ADRs of 384 patients were quantified within 6-week treatment, and the scores of movement-related ADRs at baseline and follow-up time points during treatment were obtained. The highest score record was used as the quantitative index in analysis, and genetic analysis at the genome-wide level was conducted. The SNP rs4149181 in SLC22A8 [P = 2.28 × 10−8] showed genome-wide significance, and rs2284223 in ADCYAP1R1 [P = 9.76 × 10−8], rs73258503 in KCNIP4 [P = 1.39 × 10−7], rs678428 in SMAD9 [P = 4.70 × 10−7], rs6421034 in NAP1L4 [P = 6.80 × 10−7], and rs1394796 in ERBB4 [P = 8.60 × 10−7] were found to be significantly associated with movement-related ADRs. The combined prediction model of these six loci showed acceptable performance in predicting adverse events [area under the curve (AUC): 0.84]. Combined with the function and network of the above genes and other candidate loci (KCNA1, CACNG1, etc.), we hypothesize that SLC22A8 and KCNIP4-Kv channel perform their respective functions as transporter or channel and participate in the in vivo metabolism or effects of aripiprazole. The above results imply the important function of ion transporters and channels in movement-related adverse antipsychotic effects in aripiprazole monotherapy schizophrenia patients.

Adverse Drug Reactions of Antiepileptic Drugs in Neurology Department of M.Y.H Indore, India: An Observational, Prospective Study

Background: Epilepsy is the second most common neurological disorder that affects 1 percent of global population. Since antiepileptics have narrow therapeutic index having multiple adverse drug reactions (ADRs) thus have significant safety concerns. The aim of this study was to observe adverse drug reactions due to antiepileptics in neurology department M.Y.H. Indore, India.
 Methods: An observational prospective study was done from November 2021 to January 2022. Patients having history of seizures attending neurology outpatient department at MYH Hospital, who were on antiepileptic drugs were recruited. Suspected adverse drug reaction forms were recorded and their causality assessment was done by Naranjo’s scale.
 Results: Data of total 70 patients were recorded. Males reporting ADRs due to antiepileptics were 67.1% and females 32.8%. Using Naranjo’s scale, we noted 93.3% ADRs as “probable” and 6.7% as “possible”. Common causes of prescribing antiepileptic drugs were known case of epilepsy (78.5%),old case of neurocysticercosis (11.4%),post traumatic(4.3%),gliosis (2.8%) and tuberculoma (2.8%) .Most ADRs were dermatological 76% (rashes),central nervous system (16%) (nocturnal enuresis, poor school performance, dizziness, headache, sleep disturbances, personality changes) ,Gastrointestinal (8%) (gastric irritation, nausea, vomiting and hepatotoxicity) .Most common drug for causing ADRs were sodium valproate(58.5%),carbamazepine(17.14%),phenytoin(14.2%),leviteracetam(7.1%),and lamotrigine(2.8%).
 Conclusion: Our study aimed us to know the incidence and patterns of adverse drug reactions due to antiepileptics in a tertiary care institute of central India. Despite of recent advances and novel therapies used for the treatment of epilepsy, conventional drugs like sodium valproate, phenytoin and carbamazepine still are the first choice for the management and treatment of seizures and their ADRs are very common.

Iron Infusions, Their Reactions and Efficacy Related to Dosing - a Single Center Retrospective Study

Background: Intravenous (IV) iron infusions are associated with a variety of adverse drug reactions (ADRs) including anaphylactic reactions. The Commonly used IV iron formulations are Iron sucrose (Venofer), Ferric carboxymaltose (Injectafer), Sodium ferric gluconate complex (Ferrlecit), and others. Iron sucrose has been approved by the FDA (Food and Drug Administration) for patients with iron deficiency who also have kidney disease. It is also often used off-label for iron deficiency anemia on its own. In our facility, multiple ADRs were noted with Venofer compared to other formulations. Hence, we aimed to study: 1. If altering the dose of Venofer will result in a lesser incidence of allergic reactions. 2. To determine if one preparation of IV iron has a higher incidence of adverse events than another. 3. To evaluate the efficacy after 6 to 8 weeks of completion of iron infusions, by comparing the response to various dosages and formulations. Methods: This is a retrospective chart review of 274 patients ages 18-92 who received at least one dose of Intravenous Iron at Einstein Medical Center Montgomery Outpatient Infusion Center from 01/01/21 to 10/31/21. Patients were divided into two groups based on the Venofer dosing schedule. Group D1 included patients that received any IV iron formulation from January to May 2021. In this group, Venofer dosing was 400mg x 1 followed by 300mg x2. Multiple ADRs were noticed in group D1 hence Group D2 was created. This group included patients that received any IV iron formulation from June to October 2021, where Venofer dosing was changed to 300mg x 3 doses or 300mg x 2 followed by 400mg. We collected data on age, gender, race, preparation, strength, pregnancy status, prior history of allergies and transfusion reactions, adverse drug reactions, the timing of reaction, total doses received, pre/post-medications provided to prevent or treat a reaction, outcomes of reaction, hemoglobin, iron studies before and after the infusions. Patient characteristics in both D1 and D2 groups were well balanced. Data were analyzed and summarized in descriptive measures. Efficacy of intravenous iron treatment was measured as a rise in Hemoglobin by 2gm/dl. Results: Out of 120 patients in group D1, 71 patients (59.2%) received Injectafer, out of these, 12 patients (16.9%) had ADRs, the most common reaction was hypotension, and 1 patient had an anaphylactic reaction requiring Emergency Room (ER) visit. Responders in this group were 28/71(39.4%). 10/71 (14.1%) were lost to follow-up. 48 patients (40%) received Venofer, out of which 11 patients (22.9%) had ADRs, the most common being pain in the back, and 2 patients required ER visits. Responders to the infusion in this group were 11/48 (22.9%) with 10/48 (20%) lost to follow-up. 1 patient (0.8%) received ferumoxytol, with no ADRs to report. In the D2 group, which involved a total of 154 patients, 76 patients (49.3%) received Injectafer, out of which 14 patients (18.4%) had ADRs, again the most common being hypotension, and 2 patients required an ER visit. Responders in this group were 29/76 (38.1%) and 10/76 (13.2%) were lost to follow-up. 77 patients (50%) received Venofer, out of which 9 patients (11.7%) had ADRs, the most common being hypotension and this group has not had any ER visits. Responders to the infusion in this group were 36/77(46.8%) and 9/77 (11.7%) were lost to follow-up. 1 patient (0.6%) received Ferumoxytol with no ADRs. [See Table 1]. Conclusions: Injectafer was overall the most used iron formulation in our institution. It was associated with more ADRs when compared to Venofer, including anaphylactic reactions. The most common ADR was hypotension with Injectafer, and back pain with Venofer. We found that Venofer dosing with 400mg x 1 followed by 300mg x2 was associated with the highest incidence of ADRs. Both strategies of Venofer dose modification with 300mg x 3 and schedule modification, 300x 2 followed by 400mg had greater efficacy and lesser frequency of ADRs as compared to Venofer 400mg followed by 300mg x2. Other studies have shown the benefit of Venofer in non-renal disease patients with iron deficiency. Although our study was not planned to demonstrate this outcome, our data may suggest that Venofer is beneficial for this group of patients. This should be looked into with further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence of adverse reactions to intravenously administered originator biologics in patients with rheumatoid arthritis: A 5-year retrospective study

BackgroundFew Saudi studies have examined adverse drug reactions (ADRs) in patients with rheumatoid arthritis (RA) receiving intravenous (IV) originator biologics. Therefore, this study aimed to evaluate the prevalence, types, and predictors of ADRs following long-term IV originator biologic use in patients with RA. Patients and methodsThis retrospective, single-center study included adult patients with RA who received IV originator biologics between 2015 and 2020. Medical records were reviewed and data regarding ADRs were collected and evaluated for causality using the Naranjo scale. Binary logistic regression analysis was performed to identify the odds for and factors associated with developing ADRs for each biologic. ResultsA total of 129 patients (87.6% women) with a mean (standard deviation) age of 54 (13) years were included in this study. A total of 1963 doses of tocilizumab (38.76%), rituximab (38.76%), abatacept (13.95%), and infliximab (8.53%), were administered during the study period. ADRs with a Naranjo score ≥ 1 were experienced by 103 (78%) patients, with an average of 2.2 events per patient. Infection (26.6%) and skin and mucous membrane disorders (14.18%) were the most commonly reported ADRs. Abatacept was associated with a significantly higher risk of multiple ADRs than the other biologics (adjusted odds ratio: 3.145, 95% confidence interval 1.004–9.854, p = 0.049). ConclusionThere was a high prevalence of ADRs among patients with RA receiving biologics. Abatacept was associated with a greater risk of multiple ADRs than other biologics. Infection was the most common ADR. Future multicenter longitudinal studies are warranted.

Adverse Drug Reaction Monitoring of Anticancer Drugs in Hematology Department

Background: Cancer is among the leading causes of mortality in India. Studies have reported antineoplastic agents as the common class of drugs causing Adverse Drug Reactions (ADRs). The present study aimed to conduct active surveillance of ADRs of anticancer drugs in the hematology department. Methods: A prospective observational study was conducted in 136 patients with cancer and the incidence and frequency of ADRs were assessed. The study was conducted in 6 months in a multispecialty hospital. Results: Among 136 cancer patients, All was more prevalent (39.70%); CLL, Non- Hodgkin’s Lymphoma were less prevalent (0.73%). ADRs were more prevalent in the Pediatrics department, i.e., 18.53% of ADRs were observed in patients aged <10 years. ADRs in male patients constituted 54.39%, whereas it was 45.60% in female patients. Cytarabine caused the highest number of ADRs (34.48%). The most prevalent ADR was anemia (25.60%). Conclusion: Multiple ADRs were detected in cancer patients. We found that hematological ADRs were more prevalent. Most of the ADRs were possible reactions according to Naranjo and the World Health Organization (WHO) scales.

Multiple Adverse Drug Reactions to Calcineurin Inhibitors in a Renal Transplant Patient

Calcineurin inhibitors (CNIs) are typically used to prevent organ rejection and their use has significantly improved allograft and survival rates with a marked reduction in rejection rates. However, CNIs have been associated with various side effects including nephrotoxicity, hypertension, gingival hyperplasia, hypertrichosis, hepatotoxicity, hyperkalemia, and neurotoxicity. Significant intra-patient and interpatient pharmacokinetic variability and narrow therapeutic indices make the therapy complicated. Although CNIs are essential in preventing organ rejection, higher doses could lead to toxicity, which can reduce patient tolerability and negatively affect long-term allograft survival and patient mortality. As individual patients respond differently to comparable drug levels, attaining the optimal drug level range does not ensure lack of drug toxicity or complete immunosuppressant viability. One to two adverse effects are commonly observed in patients using CNIs. However, no case about CNI-induced gingival hyperplasia, hypertrichosis, tremors, facial nerve palsy, and blepharospasm after kidney transplantation in a single patient has been reported. Our report describes the unusual case of a patient presenting with CNI-induced multiple adverse reactions.

Nationwide analysis of treatment outcomes in children and adolescents routinely treated for tuberculosis in the Netherlands.

As a vulnerable population, children and adolescents with tuberculosis (TB) are faced with many challenges, even those who live in low TB incidence countries. We aimed to evaluate factors associated with TB treatment outcomes allowing more focused interventions to support this population once diagnosed. A retrospective cohort study using a nationwide surveillance database was performed in children and adolescents (aged 0-18 years) treated for TB in the Netherlands from 1993 to 2018. Logistic regression analyses were used to estimate adjusted odds ratios (aOR) for associated factors of mortality and loss to follow-up (LTFU). Among 3253 eligible patients with known outcomes, 94.4% (95.9% children and 92.8% adolescents) were cured or completed treatment, 0.7% died during treatment and 4.9% were LTFU. There were no reported treatment failures. Risk factors of death included children aged 2-4 years (aOR 10.42), central nervous system TB (aOR 5.14), miliary TB (aOR 10.25), HIV co-infection (aOR 8.60), re-treated TB cases (aOR 10.12) and drug-induced liver injury (aOR 6.50). Active case-finding was a protective factor of death (aOR 0.13). Risk factors of LTFU were adolescents aged 15-18 years (aOR 1.91), illegal immigrants (aOR 4.28), urban domicile (aOR 1.59), unknown history of TB contact (aOR 1.99), drug-resistant TB (aOR 2.31), single adverse drug reaction (aOR 2.12), multiple adverse drug reactions (aOR 7.84) and treatment interruption >14 days (aOR 6.93). Treatment in recent years (aOR 0.94) and supervision by public health nurses (aOR 0.14) were protective factors of LTFU. Highly successful treatment outcomes were demonstrated in children and adolescents routinely treated for TB. Special attention should be given to specific risk groups to improve treatment outcomes.

Induction and Amelioration of Methotrexate-Induced Gastrointestinal Toxicity are Related to Immune Response and Gut Microbiota

As a widely used anticancer and immunosuppressive agent, methotrexate (MTX) can induce multiple adverse drug reactions (ADRs), such as gastrointestinal toxicity, the mechanisms are poorly understood. Gut microbiota has been widely reported to be associated with the onset of multiple diseases as well as treatment outcomes of different drugs. In this study, mucosal injury was observed in MTX-treated mice, leading to significant changes in macrophages (i.e., M1/M2 ratio, P < 0.05) but not in dendritic cells. Moreover, the population, diversity and principal components of the gut microbiota in mice were dramatically altered after MTX treatment in a time-dependent manner, and Bacteroidales exhibited the most distinct variation among all the taxa (P < 0.05). Bacteroides fragilis was significantly decreased with MTX treatment (P < 0.01) and tended to decrease proportionately with increasing macrophage density. Gavage of mice with B. fragilis ameliorated MTX-induced inflammatory reactions and modulate macrophage polarization. In conclusion, our results delineate a strong impact of the gut microbiota on MTX-induced intestinal mucositis and provide a potential method for the prevention of such ADRs.

Direct costs of managing adverse drug reactions during rifampicin-resistant tuberculosis treatment in South Africa.

To estimate the provider costs of managing adverse drug reactions (ADRs) to standard long-course treatment for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) according to South African guidelines. We parameterised a published Markov health state model for MDR/RR-TB with guidelines-based, bottom-up public-sector provider costing of ADR management. Frequency of ADR occurrence was extracted from the literature. Costs were estimated over 10 years, discounted 3% annually and tested using probabilistic sensitivity analysis. On average, guidelines-based costing of moderate ADRs weighted by the frequency of occurrence was US$135.76 (standard deviation [SD] US$17.18) and the cost of serious ADRs was US$521.29 (SD US$55.99). We estimated that the incremental costs of ADR management were US$380.17 annually per patient initiating MDR/RR-TB treatment. The incremental costs of ADR management for the public health sector in South Africa was US$4.76 million, 8.3% of the estimated cohort costs of MDR/RR-TB treatment ($57.55 million) for the 2015 cohort of 12 527 patients. Management of multiple ADRs and serious ADRs, which are common during the first 6 months of standard, long-course MDR/RR-TB treatment, substantially increases provider treatment costs. These results need to be taken into account when comparing regimen costs, and highlight the urgent need to identify drug regimens with improved safety profiles.

Drug-Induced Paradoxical Vocal Fold Motion

Vocal cord dysfunction, also known as paradoxical vocal fold motion (PVFM), is a disorder characterized by abnormal vocal cord adduction during inspiration. PVFM is commonly misdiagnosed as asthma because of the similarity of symptoms: cough, wheezing, chest pain, and dyspnea. We present the clinical vignette of a 36-year-old woman with juvenile rheumatoid arthritis and multiple adverse drug reactions who presented with recurrent episodes of unrecognized PVFM during skin testing for drug allergy, omalizumab treatment, and tocilizumab desensitization. Before the diagnosis of PVFM, these episodes were treated as anaphylaxis, including the administration of epinephrine. Once diagnosed and treated for PVFM, the patient did not present any further events and continued treatment for drug allergy. PVFM may be underreported in hypersensitivity reactions because of the similarity to Type 1-mediated respiratory symptoms and comorbid asthma.

Adverse reactions to fluoroquinolones in the Nigerian population: an audit of reports submitted to the National Pharmacovigilance Centre from 2004 to 2016.

Adverse drug reactions (ADRs) recorded in national pharmacovigilance databases in developed countries have been analyzed. However, adverse reactions to fluoroquinolones were observed globally despite their wide use and safety concerns. We provided information on the pattern of adverse reactions to fluoroquinolones reported spontaneously to the National Pharmacovigilance Centre (NPC), Nigeria. ADRs to fluoroquinolones reported to the NPC, over a period of 12 years, were analyzed. Evaluation was done for annual reports, age and gender of patients, type of reporter, suspected fluoroquinolones and adverse reactions, onset and outcome of ADRs, and causality. A total of 18527 ADR reports were received by the NPC. Antibiotics accounted for 1371(7.4%) of the total reports and fluoroquinolones accounted for 256 (18.7%) cases. A total of 540 ADRs due to fluoroquinolones was experienced by the patients. Multiple ADRs were experienced by 165 (65%) patients. Norfloxacin (2; 0.8%), moxifloxacin (3; 1.2%), ofloxacin (10; 3.9%), ciprofloxacin (112; 43.8%), and levofloxacin (129; 50.4%) were responsible for the ADRs. Neurological disorders (121; 22.4%), gastrointestinal disorders (118; 21.9%), and skin‐appendage disorders (116; 21.5%) were the most reported ADRs, while pruritus (41; 7.6%), abdominal pain (34; 6.3%), vomiting (34; 6.3%), and skin rash (27; 5.0%) were the most frequently reported specific ADRs. Thirty‐four (6.4%) patients experienced serious ADRs. Fluoroquinolones accounted for a small but significant proportion of ADRs spontaneously reported to the NPC in Nigeria. Ciprofloxacin and levofloxacin were the two most culpable fluoroquinolones due to their inappropriate use or increased use in multi‐drug resistant tuberculosis (MDR‐TB) treatment.

Quality of life in children with adverse drug reactions: a narrative and systematic review

Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases.

Identifying the causative proteins of similar side effect pairs to explore the common molecular basis of these side effects.

Drug side effects, or adverse drug reactions (ADRs), have become a major public health concern and often cause drug development failure and withdrawal. Some ADRs always occur concomitantly. Therefore, identifying these ADRs and their common molecular basis can better promote their prevention and treatment. In this paper we predicted the potential proteins for ADR pairs with similar mechanisms based on three layers of information: (i) the drug co-occurrence between a pair of ADRs; (ii) the correlation between a protein and an ADR pair based on the co-occurrence of drugs and (iii) the interaction between these proteins within the protein-protein interaction (PPI) network. The methods of randomization and functional annotation are used to investigate and analyze the relation between causative proteins and similar ADR pairs. The prediction accuracy of the relation between similar ADR pairs and related proteins reached 80%, and it increases with the number of drugs shared by the ADR pairs. From the ADR network made of single ADRs from predicted similar ADR pairs, we found that some ADRs are involved in multiple ADR pairs. The functional analysis of these ADR-related proteins suggests that a similar molecular basis is shared by multiple ADR pairs containing the same ADR, and these ADR pairs are almost caused by the same drug sets. The results of this study are reliable and provide a theoretical basis for the better prevention and treatment of ADRs that always occur concomitantly.

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

BackgroundData collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas.ObjectivesThe aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner.MethodsWe used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength.ResultsWhen applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five patients exhibited a significant difference (p < 0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05).ConclusionsThe developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-014-0145-z) contains supplementary material, which is available to authorised users.

Network Characteristic Analysis of ADR-related Proteins and Identification of ADR-ADR Associations

Adverse drug reactions (ADRs) are caused by interactions between drugs or their metabolites and specific proteins. Knowledge of these proteins is important for facilitating mechanistic research of ADRs and new drug discovery. Here, we identified 41 network modules from an ADR-protein network; analysed the function of each module; revealed the potential accompanying actions of the ADRs and the new ADR-related proteins (ADRPs) to a unique ADR and studied the characteristics of composition, subcellular location and tissue distribution of these ADRPs by comparing them with drug-related proteins (DRPs). The results indicated that ADRs are mainly caused by risk drug-related proteins (RDRPs) and that drug off-target effects are a secondary cause. Biological processes that enzymes involve are the main reason for the occurrence of ADRs. However, drug-related transporters have a higher risk of inducing ADRs than drug-related enzymes do, and ADRPs locating in the cell membrane tend to induce multiple ADRs.

Adverse drug reactions in medical intensive care unit of a tertiary care hospital

Patients in the intensive care unit (ICU) have multiorgan dysfunction as well as altered pharmacokinetic parameters. Hence they are susceptible to adverse drug reactions (ADRs). The objective of the study is to assess the characteristics of ADRs among inpatients in the medical ICU and to compare the same with patients who have not experienced ADRs. Prospective, observational study for a period of 1 year in medical ICU of a tertiary care hospital. Relevant data of patients with ADRS were analysed. Characteristics of patients with and without ADRs were compared. Of 728 patients admitted in medical ICU, 222 (28.4%) had ADRs. Multiple ADRs (38.7%) implicated by the same drug and serious ADRs (37%) were noticed. Renal/electrolyte system (21%) was most commonly involved. Clinical spectrum included acute renal failure (ARF, 11.4%), hepatic injuries (5.4%), haematological dysfunction (4.2%), seizures (3.3%), upper gastrointestinal bleed (3.3%) and cutaneous ADRs (3.3%). Antimicrobials (27%) were the commonly implicated drug class. The most commonly implicated drug was furosemide (6.8%). Infrequently reported ADRs included azithromycin-induced erythema multiforme, leflunamide-induced erythema multiforme and vasculitis, ceftazidime-induced seizures and ceftriaxone-induced hepatitis. Co-morbidity, polypharmacy and duration of stay were significantly higher in patients with ADRs compared to those who have not experienced ADRs. Three patients died. High incidence of serious and multiple ADRs noticed. A wide clinical spectrum of ADRs and infrequently reported ADRs to newer drugs were also observed.

Adverse drug reactions in nephrology ward inpatients of a tertiary care hospital

Adverse drug reactions (ADRs) are important causes of hospital admissions and inpatient complications. Renal dysfunction has a role in occurrence of ADRs. (1) To study the characteristics of ADRs among inpatients in Nephrology ward of a tertiary care hospital and (2) to compare these characteristics between patients with renal dysfunction and patients with normal renal function in same population of patients with ADRs. A retrospective study of inpatients with ADRs (July 2005-June 2006) in Nephrology ward of a tertiary care hospital. ADR characteristics were analyzed using descriptive statistics. Comparisons were made between normal renal function group and renal dysfunction group by t-test and Chi-square test. Of 1,464 case records, 244 (17%) patients were included. Two hundred sixty-seven drugs contributed to 294 ADRs. Serious ADRs accounted for 12% of the total ADRs. Renal/ electrolyte system (44%) was the most common organ system involved. Major clinical spectrum of ADRs included acute renal failure (22%), hypo/ hyperglycemia (13%), hyper/ hypokalemia (13%), bone marrow suppression (5%) and hepatic injuries (4%). Prednisolone (12%) was the most commonly implicated drug. Mean time to revert was 13+/-7.2 days. Three patients died. On comparing patients with normal renal function (n=80) with those suffering from renal dysfunction (n=164), polypharmacy, serious ADRs, multiple ADRs, longer time to recover, longer period of hospitalization were found to be more frequent among the renal dysfunction group (P CONCLUSIONS: High incidence of ADRs, especially serious and life-threatening ADRs, was noticed. A wide spectrum of ADRs was observed. Renal dysfunction showed a significant impact on various characteristics of ADRs.

Adverse Drug Reactions Following Nonresponse in a Depressed Patient with CYP2D6 Deficiency and Low CYP 3A4/5 Activity

A 47-year-old male taxi driver experienced multiple adverse drug reactions during therapy with clomipramine (CMI) and quetiapine for major depressive disorder, after having been unsuccessfully treated with adequate doses of mirtazapine and venlafaxine. Drug serum concentrations of CMI and quetiapine were significantly increased and pharmacogenetic testing showed a poor metabolizer status for CYP2D6, low CYP3A4/5 activity and normal CYP2C19 genotype. After reduction of the CMI dose and discontinuation of quetiapine, all ADR subsided except for the increase in liver enzymes. The latter improved but did not normalize completely, even months later, possibly due to concomitant cholelithiasis.

Approach to the patient with multiple antibiotic sensitivities.

Allergists sometimes are asked to evaluate patients who have experienced multiple adverse drug reactions. By the time the patient reaches the allergist, the referring physician, as well as the patient, often are frustrated. Each seeks a quick and simple answer regarding the particular drugs the patient may safely receive. Unfortunately, however, in most instances, simple answers cannot be given. Currently we have limited knowledge of the mechanisms and of the clinically-relevant drug metabolites responsible for many of the reactions demonstrated and, for these reasons, we have few valid diagnostic tests that are able to provide clear-cut answers for our patients who present with multiple drug "allergies." Despite these limitations, using accurate and complete historical information along with limited diagnostic testing, logical and practical management approaches can be devised. In addition, due to new exciting data that are being generated from basic research studies in drug allergy, the mechanisms underlying the immunopathology of many drug reactions are becoming more clear. Through the acquisition of scientific information of this type, it is hoped that valid diagnostic tools soon will be developed so that definitive answers, desired by both the patient and the referring physician, can be provided.