Classification Of Adverse Drug Reactions Research Articles

Spontaneous Reporting of Adverse Drug Reactions through Electronic Submission from Regional Society Healthcare Professionals in Korea

PurposePharmacovigilance Research Network built a spontaneous reporting system and collected adverse drug reactions (ADRs) by electronic submission (e-sub) in Korea. We analyzed ADRs spontaneously reported through e-sub from regional health professionals.Materials and MethodsNine hundred and thirty three ADR cases were collected and analyzed from January to December in 2008. "A matter" was defined as one symptom matched to one culprit drug included in an ADR case. We collected and analyzed e-sub ADR cases and matters to determine common culprits and organ specified ADR matters.ResultsThere were 3,049 matters in 933 ADR cases for 1 year, and 3.3 matters per case were reported. In organ specific ADR classification, skin reactions which took the first place in 866 matters (28%) included urticaria and rash. The next cases were neurologic symptom (624 matters, 21%) and gastrointestinal symptom (581 matters, 19%). Doctor (53%) and pharmacist (31%) were the most important participants in e-sub spontaneous reporting system, and 3% of ADR cases were reported by patients or their guardians. WHO-Uppsala Monitoring Center causality assessment results showed certain 10.6%, probable 37.7%, possible 41.7% and below unlikely 10.0%. Culprit drugs were antibiotics (23.4%), neurologic agents (14.7%) and non-steroidal anti-inflammatory drugs (9.4%).ConclusionIn our study, antibiotic was most common culprit drug, and skin manifestation was most common symptom in e-sub ADRs collected from regional healthcare practitioners in Korea.

Bases for the study of the safety of medicines. The spectrum of rare and unexpected ad-verse reactions of bisphosphonates

The paper presents a classification of adverse drug reactions and their characteristics. Bisphophonates (BP) that are have been prescribed for more than 30 years to prevent and treat all forms of osteoporosis (OP) and recognized as first-line drugs for its treatment are used as an example to see the history of investigating rare and unexpected adverse reactions. The direct correlation between the rare adverse reactions of Ps and their use remains to be proven today. The proposal to reduce the prescriptions of BPs is unfounded. The evidence for the efficacy and safety of BPs in OP has been obtained and confirmed by multiple trials and many years X real practice. Alendronate (fosavance) is the most studied BP now.

Causality Assessment of Cutaneous Adverse Drug Reactions

BackgroundCutaneous adverse drug reactions (ADRs) are the most common adverse reactions attributed to drugs. A systematic and effective approach to a patient with suspected drug eruption allows for prompt recognition, classification and treatment of cutaneous ADRs. A standardized and effective approach for objective causality assessment is necessary to make consistent and accurate identification of ADRs.ObjectiveAlthough the Naranjo algorithm is the most widely used assessment tool, it contains many components which are not suitable for clinical assessment of ADRs in Korea. The purpose of this study is to compare correlations of the Naranjo algorithm and the Korean algorithm to evaluate usefulness of both algorithms in order to make a causal link between drugs and cutaneous ADRs. In addition, this study classifies the clinical types and causative agents of cutaneous ADRs.MethodsThe authors retrospectively reviewed the clinical types and laboratory findings of patients who were diagnosed with cutaneous ADRs in the dermatology clinic at Gil hospital. One hundred forty-one patients were enrolled in this evaluation. The causal relationship of ADRs was assessed by using the Naranjo algorithm and Korean algorithm (version 2.0).ResultsA cross-tabulation analysis was applied to the Naranjo algorithm and Korean algorithm (version 2.0). Simple correlation analysis and a Bland-Altman plot were used for statistical analysis. Correlation analysis confirmed that the two assessment algorithms were significantly correlated. Exanthematous eruptions (68.8%), Stevens- Johnson syndrome (10.6%), and urticaria (8.5%) were the most common types of cutaneoues ADRs. The most common causative agents were antibiotics/antimicrobials, antipyretics/non-steroidal anti-inflammatory drugs, and central nervous system depressants.ConclusionThe Naranjo algorithm and Korean algorithm (version 2.0) were significantly correlated with each other, and thus reliable assessment methods to determine cutaneous ADRs.

Development of a combined system for identification and classification of adverse drug reactions: Alerts Based on ADR Causality and Severity (ABACUS): Table 1

Currently, adverse drug reaction (ADR) causality and severity are assessed using different systems but there is no standard method to combine the results. In this work, a combined ADR causality and severity assessment system, including an online version, was developed. Logical rules were defined to translate the score obtained from the system into three alert zones: green, amber, and red. The alert zones are useful for triaging ADR cases as they help define the seriousness of the ADR and the urgency of the responses required. This new scoring system may be useful for clinicians, investigators, and regulators seeking information on the likelihood of a drug causing an adverse reaction, and whether an adverse reaction is sufficiently dangerous for the drug to be withheld or undergo further investigation.

Adverse events to Houttuynia injection: A systematic review

To systematically assess the main clinical features of Houttuynia injection-associated adverse drug reactions (ADRs), as described in published reports, and to contribute to the post-marketing re-evaluation and clinical practices of Houttuynia injection. We searched the electronic databases- PubMed, EMBASE, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Science and Technology Journal Full-text Database (VIP) and the Chinese Biomedical Disc (CBMdisc), for articles published through June 2010. We then extracted and analyzed the data. A total of 645 articles were included, with a total of 1232 ADR cases reported. Respiratory diseases accounted for 52.44% of all cases of Houttuynia injection ADRs, followed by reproductive system diseases (4.30%) and urinary system diseases (3.73%). Multiple systems or organs were involved in the ADRs, the top five were: respiratory system (37.42%), skin (34.66%), digestive system (25.49%), circulatory system (25.41%), and nervous system (23.96%). Serious systemic adverse reactions accounted for 22.56% of total ADRs. Of the reported 1,232 ADR cases, 286 ADR cases reported previous allergies in detail; allergy to penicillin accounted for 15.03% of the total cases with the allergic history, followed by unknown drugs (8.05%), and sulfonamides (3.15%). Among the ADR cases, Houttuynia injection was commonly used together with cephalosporins, penicillins, and macrolides. Macrolides combined with Houttuynia injection showed higher ADR risk than Houttuynia injection used alone (RR = 8.80, 95% CI 6.12 to 12.65, P < 0.0001). The ADR risk for intravenous injection of Houttuynia injection was higher than that of intramuscular injection (OR = 6.86, 95% CI 1.88 to 56.95, P= 0.0016). We used the WHO ADR Classification Criteria to divide the ADR cases into four grades. There were 22.56%, 36.28%, 16.48%, and 24.68% cases of Grade I, II, III, and IV, respectively. Anaphylactic shock accounted for 58.99% of the most serious ADRs (Grade I). All cases of death were caused by allergic shock, except one, who died of multiple organ failure caused by anaphylactic purpura. The fastest-onset three ADR cases occurred in one minute after injection. The respiratory system was the most common system treated in Houttuynia injection ADR cases. It was also the most common site of ADR symptoms. The ADRs of Houttuynia injection were serious. The precautions should be taken to prevent the anaphylactic shock. Intravenous injection and the combination with with cephalosporins, penicillins, and macrolides increased the ADR risk of Houttuynia injection.

Discrepancies in reported drug use in geriatric outpatients: Relevance to adverse events and drug-drug interactions

Background: Increased age is associated with polypharmacy. Polypharmacy is a risk factor for severe adverse drug reactions (ADRs) and is associated with an increased risk of mortality. Objectives: The main goal of the current study was to describe the frequency and relevancy of discrepancies in drug use in Dutch geriatric outpatients as reported by the patients and their caregivers, documented by the referring general practitioner (GP), and registered by the public pharmacy. The frequency of medication discrepancy adverse patient events (MDAPEs) was also recorded. In addition, possible contributing factors—such as increasing age, cognitive status and depressive symptoms, the number of medications used, the number of physicians visited by the patient, and the presence of a caregiver to supervise medication use—were studied. Methods: This was a prospective descriptive study conducted at the geriatric outpatient clinic of a teaching hospital. Between January 1 and May 1, 2005, consecutive patients were included if they were aged >65 years, reported use of ≥1 medication, and if they could understand the goals and consequences of participating in the study. The medications described by geriatric patients and their caregivers were compared with the drugs listed by their GP. The pharmacies of the referred patients were asked to send a description of the drugs distributed in the 6 months preceding the patient's visit to the geriatric outpatient clinic. The classification of ADRs and undertreatment as clinically relevant was done by study investigators who were blinded for the presence of discrepancy. Results: A total of 120 outpatients were included. The mean (SD) age of the study patients was 82.3 (6.8) years; 71.7% were women. Of the 120 patients, 113 patients (94.2%) reported taking >1 drug and 88 (73.3%) were prescribed ≥4 drugs. At least 1 discrepancy between the medication lists of the patients, GP, or pharmacy was present in 104 of the 120 patients (86.7%). In 90 patients (75.0%), there was ≥1 discrepancy between the medication reported by the patient and the GP. Patients with ≥1 discrepancy reported taking a higher mean number of drugs and had more prescribing physicians in addition to their GP. Twenty-nine patients (24.2%) experienced an MDAPE involving the use of drugs the GP had not correctly described in the letter of referral. The pharmacy was unaware of the use of medication involved in an MDAPE in 2 patients. Conclusions: Geriatricians should assume that the medication lists supplied by GPs are incomplete or incorrect, and be aware that in ~25% of patients, symptoms may be caused by medication use inaccurately described in the referral. Reports by the community pharmacy may supply valuable additional information. Because there are also discrepancies between patients and pharmacies, medication use from a database—with data from prescribing physicians and pharmacy systems—will still have to be confirmed by the patient.

Nationwide Survey of Subjectively Reported Adverse Drug Reactions in Sweden

Adverse drug reactions (ADRs) and the safety of drugs continue to be widely discussed. However, information on the prevalence of subjectively experienced ADRs (SADRs) and their subsequent burden in the general population is largely lacking. To analyze, from an epidemiologic perspective, SADRs with respect to occurrence and health status. A cross-sectional mail survey to a random national sample in Sweden of inhabitants aged 18-84 years was conducted; 61% (N = 4875) of the sample answered the questionnaire. Self-reported SADRs occurring during a 2-week period of using prescription, over-the-counter (OTC), or herbal drugs were classified according to Meyler's classification of ADRs. Self-perceived health status was assessed with a visual analog scale graded from 0 (worst possible health/death) to 1 (perfect health). SADRs were reported by 6.4% of the total study sample, 10.2% of the 2851 users of prescription drugs, 1.0% of the 2862 users of OTC drugs, and 0.1% of the 1352 users of herbal drugs. Of the total sample, 3.3% reported SADRs of the nervous system, 2.6% of the gastrointestinal system, and 0.6% of the cardiovascular system. Users of prescription drugs with SADRs reported a mean health status score of 0.655, while those who did not report SADRs scored 0.744. Among users of OTC and herbal drugs, the corresponding scores were 0.720 and 0.818, respectively. Those in the population who did not use any drugs rated their health status as 0.846. Both the prevalence of SADRs and the magnitude of the decrease in subjective health status in respondents experiencing them reflect the importance of individual subjective perceptions for public health. However, in a cross-sectional study like this, causal relationships cannot be firmly established. Further, other factors, such as comorbidity or disappointment with treatment outcomes, could be associated with the decrease in health status.

Understanding Adverse Drug Reactions and Drug Allergies: Principles, Diagnosis and Treatment Aspects

Adverse Drug Reactions (ADRs) and drug allergies- as a subset of ADRs- make a significant public health concern, complicating 5 to 15% of therapeutic drug courses. They may result in diminished quality of life, increased physician visits, health care costs, hospitalizations, and even death. The incidence of serious ADRs in hospitalized patients was estimated to be 6.7% and for fatal ADRs to be 0.32%, so recognizing and taking action on ADRs is an important aspect of medication management. Allergic reactions to drugs refer to those ADRs that involve immune mechanisms which account up to 15% of ADRs and can be identified as being a type I through IV immune reaction that the most common immunologic mechanism is IgE-mediated- type I reaction. Clinical manifestations of allergic reactions range from pruritus and rash to serious reactions such as systemic anaphylaxis and cardiovascular emergencies and they are responsible for 2-3% of hospitalized patients. Health professionals should be aware of the ADRs presenting clinical features and the risk factors and should be able to differentiate between allergic and non-allergic adverse drug reactions. This will lead to increased opportunities to review drug selection and prescribing practices affecting patients' outcome. This article will review the definition and estimated incidence, the features, classification and types of ADRs and drug allergies and related patents. It will highlight the role of detecting, reporting, and assessing suspected ADRs and drug allergies in the most clinically relevant drugs group. Priorities in the evaluation and management of the conditions of patients who have experienced allergic and non-allergic drug reactions also will be discussed.

An agenda for research on adverse drug reactions

An agenda for research on adverse drug reactions

Adverse drug reaction reporting by nurses in Sweden

To investigate whether nurses could be a useful tool for improving the reporting rate of adverse drug reactions (ADRs). Furthermore, we wanted to study how physicians working at the study departments would respond to nurses as reporters of ADRs and if the reporting from the nurses affected the reporting rate from the physicians. Three departments of internal medicine and one unit for orthopaedics were selected for the study. Nurses with special drug responsibilities were invited to participate. At the start of the study period, the nurses received an introduction with background, objective, method and other practical issues concerning the study. After this, an education programme about ADR reporting, definitions, and ADR classification according to mechanism and organ system was given. To study their knowledge about and attitude towards ADRs, a questionnaire was handed out to the nurses. A questionnaire was also handed out to all physicians at the participating departments in order to investigate their attitude towards nurses as reporters of ADRs. Fifty-four nurses participated in the study. During the study period, a total number of 23 reports with 39 ADRs were sent to the regional centres by the nurses. Seventeen (74%) of the reports were assessed as serious. Eight of the 39 ADRs were unlabelled and all reports were considered appropriate. The reporting rate from the physicians during the study period was similar to the previous year, indicating that the nurses contributed with additional reports. At the end of the study, the nurses thought that they had enough knowledge to report ADRs. Sixty-eight percent of the physicians did not object to nurses being included as reporters of suspected ADRs. Adverse drug reaction reporting by nurses could improve the overall safety of drugs.

Unity from diversity: the evidential use of anecdotal reports of adverse drug reactions and interactions

Anecdotal case reports contribute about one-third of the published literature on adverse drug reactions and interactions, but are regarded as providing poor-quality evidence. However, they can occasionally provide proof of cause and effect, and there are many other reasons for publishing them. Because an anecdote is a narrative, narratological paradigms from literature, art, and music can show how we can make evidential use of anecdotes. Useful paradigms are the dramatic unities (of time, place, and action), comprehensive catalogues, and pattern formations. Here I give examples of each of these types of paradigm and show how they can be used to interpret anecdotes about adverse drug reactions and interactions. The dramatic unities show how a proper classification of adverse drug reactions can be achieved, according to dose-relation, time-course, and susceptibility factors; use of this classification should improve the evidential use of anecdotal reports. A high background incidence of the effect (the medical equivalent of subplots, which violate the unity of action) makes it more difficult to detect adverse drug effects using anecdotal reports. To make best evidential use of the corpus of anecdotal reports of adverse drug reactions, comprehensiveness is important: each suspected adverse reaction should be reported in detail and reactions should be reported in sufficient numbers for proper classification and for patterns to be recognized. One form of pattern recognition, teleoanalysis of data, should, when possible, include not only randomized controlled trials and observational studies, but also case series and anecdotal reports.

Validation d’une échelle de mesure : exemple de l’échelle française d’évitabilité des effets indésirables médicamenteux

Adverse drug reactions (ADRs) have been recognised as an important cause of hospital admission. Most of these drug-related admissions were expected ADRs and, thus, partly preventable. However, as far as we know, the assessment of the preventability of ADRs was addressed in only two studies performed in France. In contrast, several other studies have been performed, mainly in the USA, and using different methods of assessing preventability. None of these methods were clearly evaluated with regard to reproducibility, validity or relevance. The purpose of this study was to initiate the validation of a French preventability scale. Here, we propose the first two phases of validation: the content validity and reliability of the scale. A working group of pharmacovigilance experts has been specifically established for this purpose. The content validity was assessed by collecting items representative of preventability. The choice and the formulation of items and a proposal of a score (global and for each item) were adopted after the consensus of the experts. A definitive version of the ADR preventability scale was used for the assessment of reliability. During the second phase, experts independently tested the new scale from observations of ADRs (49 central nervous system haemorrhages with antivitamine K). The concordance of the experts’ judgements was calculated using two statistical methods (Kappa statistic and correlation coefficient). The content validity phase was performed during several workshops where experts discussed the choice and formulation of the best items. We decided to construct a scale with a small number of items, allowing a rapid evaluation of the preventability of ADRs. On the basis of a global score, four categories of preventability of ADRs (“preventable”, “potentially preventable”, “unclassable”, “not preventable” ADRs) were proposed. The agreement of experts regarding the global score was low, with a poor correlation coefficient value (coefficient interclass = 0.491). Classification of ADRs in the four categories by the experts showed discrepancies (Kappa = 0.1136). The preventability assessment using this scale was feasible, although poor concordance between the judges has raised some questions. Several experts found use of this scale difficult in terms of a clear understanding of the items, and found that two of them were redundant. We have oversimplified some items and revision of their formulation will be necessary. Moreover, most of ADR notifications were poorly documented, resulting in a frequent choice of an “unevaluable” item. This represented an important bias in the calculation of the global score. This experience suggests the need for further studies to improve this French ADR preventability scale and validate it in differing circumstances, in order to provide a useful tool to enhance the rational use of drugs.

Classification of ADRs: a proposal for harmonization and differentiation based on the experience of the Comprehensive Hospital Drug Monitoring Bern/St. Gallen, 1974-1993.

The present paper deals with the classification of adverse drug reactions (ADRs) according to today's largely accepted pathomechanisms. The classification system applied, relies primarily on the proposals of Rawlins and Thomson with type A ('augmented') and B ('bizarre') reactions. In the database of the Comprehensive Hospital Drug Monitoring (CHDM) Bern/St. Gallen on 48,005 consecutively hospitalized patients, ADRs had been attributed to 10 different pathomechanisms. These permit a versatile new system, easily adaptable to expanding knowledge. If we look at the 12,785 ADRs registered in the CHDM Bern/St. Gallen from 1974 to 1993, 76% were of type A, 13% of type B, and 11% of a pathomechanism not yet defined (type X). The main subgroups were A1 'not specified' in type A, Ba allergic/immunological and Bpa pseudoallergic/anaphylactoid in type B. Dose-related (A2) and drug-related reactions (A4, intolerance in a restricted sense), drug-to-drug interactions (A5), rebound/withdrawal effects (A6) and secondary reactions (A7) represented smaller subgroups. Patient-related reactions (A3, 'idiosyncrasy' in the strict sense) were not assessed. Today's algorithms for ADRs mainly rely on pharmacological, i.e. type A reactions. For most of the type B reactions adaptations including the experience of allergists, clinical immunologists and infectious disease specialists should be respected.

Safety of Anaesthetic Drugs

This short book is a compilation of four review articles published in 1997 and 1998 in CNS Drugs and Drug Safety. The main objective of the book is to discuss the clinically significant drug interactions and adverse effects of most commonly used anaesthetic drugs. However, in the foreword the editor points out that drug interactions with neuromuscular blockers are not included ‘… because of the availability of recent reviews on this topic’. I found this a little odd, since the book itself is a collection of recent reviews. Each chapter is exhaustively referenced, as you might expect from a series of review articles, to the extent that there are just over 30 pages of references out of a total of 101. There are also 29 tables and figures. The first chapter, on adverse effects of general anaesthetics, contains a classification of adverse drug reactions and systematically covers the effects of commonly used anaesthetics on the various organs and systems. The next chapter covers the incidence, mechanism and management of clinically significant drug interactions with general anaesthetics. There are a number of tables summarising the pharmacokinetic and pharmacodynamic interactions between anaesthetic drugs and classes of drugs (rather than specific drugs) which patients may be taking or require in the peri-operative period. These tables include the mechanism and suggested management of the interaction, and provide a useful summary for those of us who find these facts hard to remember. The third chapter covers the adverse effects of neuromuscular blockers and their antagonists, but not their interactions. As with the first chapter this is divided into the effects on the various organs and systems. The final chapter covers the adverse effects and drug interactions associated with local and regional anaesthesia. Again the logical progression through the systems takes place, with discussion of the features, mechanism and treatment of the adverse effects. Finally there are tables of the pharmacokinetic and pharmacodynamic interactions of local anaesthetics, as in the second chapter. I have never found pharmacology texts particularly readable, and this one is no exception, because of the prodigious number of facts on each page. I was given the book to read at the same time as trying to find the answers to some recent Primary FRCA multiple choice questions. I found that as long as the question was within the scope of the articles, the answer was usually there. This brings me to my main criticism of the book. As far as it goes it is informative, but it doesn't cover (apart from the involvement in interactions) any of the drugs which we use which are not anaesthetics. Exam candidates and practising anaesthetists alike still need to know about the safety of premedicants, sedatives, opioids, anti-emetics, antibiotics, inotropes and vasodilators to name but a few. For this reason, I am uncertain whether this book has a niche in an already crowded market.

Measuring side effects of psychopharmacologic medication in individuals with mental retardation and developmental disabilities

To various degrees, psychopharmacologic medications are associated with side effects. Despite improvements in newer psychopharmacologic medication, monitoring for side effects remains important for individuals with mental retardation and developmental disabilities for a number of reasons, of which perhaps the most important is that many of these individuals cannot effectively verbally communicate the presence of side effects. This article reviews four basic areas. The first is classification of adverse drug reactions (ADRs) and basic terminology such as the difference between an ADR, side effect, adverse drug event, and adverse event. Second, the methods to approach ADRs are reviewed from an organizational, research, and applied individual perspective. Third, applied side effects rating scales are reviewed. Fourth, methods to determine the likelihood that a clinical manifestation indeed represents a side effect are reviewed. Although no one method will detect all side effects and although all methods generally detect more adverse events or clinical manifestations than actually turn out to be side effects, the material may allow for more structured monitoring of psychopharmacological medication side effects beyond general impression. MRDD Research Reviews 1999;5:348–359. © 1999 Wiley-Liss, Inc.

Allergy and adverse drug reactions

This review begins with a classification of adverse drug reactions and a summary of those features that distinguish allergic from toxic and idiosyncratic reactions. Factors that influence the risk of developing drug allergy are then reviewed, followed by a discussion of the known and suspected immunologic mechanisms responsible for the development of drug allergy. The next section-on the types of clinical reactions-begins with the reactions that are mediated, or suspected of being mediated, by antibodies of the immunoglobulin E class. These are followed by a description of reactions involving single organ systems and those involving several systems. The next section reviews the cutaneous reactions that are sometimes due to drug allergy, and those that may be mistakenly blamed on drug allergy. This is followed by a discussion of pseudoallergic drug reactions-caused by toxicity or side effects of some drugs. The review concludes with a discussion of the prevention and treatment of reactions that are allergic or commonly suspected of being allergic.