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Biomedical subjects

S R Knowles

Publications and source records attributed to S R Knowles.

At least 19 recordsLinked to original sources
PubMed2001

Reporting of fatal adverse drug reactions.

OBJECTIVES: To review the reports of fatal adverse drug reactions (ADRs) submitted to the Ontario Medical Association Adverse Drug Reactions Monitoring Program between 1990 and 1994; to identify drugs associated with fatal outcomes; and to assess the causative role of the drug in these events and the completeness of the data in these reports. METHODS: Drug(s) identified on each ADR report as being responsible for the reaction were considered. Agents were classified by the Anatomical Therapeutic and Chemical classification system. The causality of each ADR report was evaluated by using an algorithmic rating scale. RESULTS: From the Ontario Medical Association database, 97 cases of ADRs that resulted in death were reviewed. One hundred fourteen medications were implicated as "suspect" drugs in the 97 deaths. The most commonly implicated drug classes were musculoskeletal agents, blood and blood-forming organ agents, and nervous system agents. Patients over 65 years of age comprised 60% of this series. After independent assessment as to causality, 13% of the cases were rated as probable, 86% were rated as possible and 1% were rated as doubtful. Seventy per cent of reports did not include information regarding medical history. Forty-two per cent of cases failed to provide adequate information to evaluate the feasibility of the time to onset of the ADR. The use of concomitant drugs was not reported in 12% of cases. CONCLUSIONS: The drugs most frequently implicated in fatal ADRs were consistent with those reported in other studies. Algorithmic causality assessments were of limited value in these reports. The completeness of the reports and adequacy of the information were poor. The type of reporting forms and information provided were not homogenous. There is a need to improve quality of reporting and harmonize reporting forms between monitoring bodies. The feasibility of unique data collection forms and obligatory reporting for fatal ADRs should be considered.

Adult↗
PubMed2000

Idiosyncratic drug reactions: the reactive metabolite syndromes.

Idiosyncratic drug reactions are unpredictable reactions that can result in significant morbidity and mortality. Severe reactions are often characterised by fever and internal organ involvement. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. Furthermore, because of the lack of consensus regarding definition of these syndromes, reporting, and therefore epidemiological data, are often unreliable. Research is needed to explore further the pathophysiology of these reactions, so that better diagnostic tests and treatment methods can be developed.

Drug Hypersensitivity↗
PubMed2000

Cost-effectiveness analysis of six strategies for cardiovascular surgery prophylaxis in patients labeled penicillin allergic.

The cost-effectiveness of different approaches to antimicrobial prophylaxis for cardiovascular surgery patients labeled penicillin allergic was studied. A decision-analytic model was used to examine the cost-effectiveness of six strategies for antimicrobial prophylaxis in cardiovascular surgery patients at a tertiary care hospital. The strategies consisted of (1) giving vancomycin to all patients labeled penicillin allergic, (2) giving cefazolin to all patients labeled penicillin allergic, (3) giving vancomycin to all patients with a history suggesting an immunoglobulin E (IgE)-mediated reaction to penicillin and cefazolin to patients without such a history, (4) administering a penicillin skin test to patients with a history suggesting an IgE-mediated reaction to penicillin and giving vancomycin to patients with positive results and cefazolin to all others, (5) skin testing all patients labeled penicillin allergic and giving vancomycin to those with positive results and cefazolin to those with negative results, regardless of history, and (6) skin testing all patients and giving vancomycin to those with positive results or a history suggesting an IgE-mediated reaction to penicillin and cefazolin to all others. Giving cefazolin to all patients labeled penicillin allergic was the least expensive strategy but was associated with the highest rate of both anaphylactic and non-life-threatening serious reactions. Selective use of vancomycin in patients with a history suggesting an IgE-mediated reaction to penicillin was associated with an added cost and a slightly lower rate of anaphylaxis. Although skin-testing strategies may decrease both non-life-threatening and anaphylactic reactions, the incremental cost was high. When vancomycin was given to all patients labeled penicillin allergic, the incremental cost was very high. A decision-analytic model indicated that selective use of vancomycin is more cost-effective than indiscriminate use of vancomycin for surgical prophylaxis in cardiovascular surgery patients labeled penicillin allergic.

Anti-Bacterial Agents↗
PubMed1999

Anticonvulsant hypersensitivity syndrome: incidence, prevention and management.

Although the anticonvulsant hypersensitivity syndrome was first described in 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1,000 to 10,000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (phenobarbitone) and carbamazepine] are the most frequently involved drugs; however, there have also been several cases of anticonvulsant hypersensitivity syndrome associated with lamotrigine. Fever, in conjunction with malaise and pharyngitis, is often the first sign. This is followed by a rash which can range from a simple exanthem to toxic epidermal necrolysis. Internal organ involvement usually involves the liver, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 months after occurrence of symptoms. The aromatic anticonvulsants are metabolised to hydroxylated aromatic compounds, such as arene oxides. If detoxification of this toxic metabolite is insufficient, the toxic metabolite may bind to cellular macromolecules causing cell necrosis or a secondary immunological response. Cross-reactivity among the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants. Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimum battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticosteroids are usually administered if symptoms are severe. Patients with anticonvulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants; benzodiazepines, valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic acid should be used very cautiously in the presence of hepatitis. There is no evidence that lamotrigine cross-reacts with aromatic anticonvulsants. In addition, family counselling is a vital component of patient management.

Anticonvulsants↗
PubMed1999

Adverse effects of antiepileptics.

When choosing an anticonvulsant drug, factors such as efficacy, pharmacokinetics, cost, teratogenic effects and potential adverse effects of the drug, and age and sex of the patient must be considered. Adverse effects are observed in up to one-third of patients on anticonvulsant therapy and are divided into two groups - common dose-related toxicity and idiosyncratic toxicity. Both types of adverse events associated with anticonvulsants are discussed according to the organ system affected. Postmarketing surveillance of the newer anticonvulsants is vital to monitor potentially rare idiosyncratic reactions or chronic toxicities.

Anticonvulsants↗
PubMed1998

The risks of systemic corticosteroid use.

Because of their potent antiinflammatory and immunosuppressive properties, systemic corticosteroids are used to modify a vast array of diseases. This class of drugs, however, has the potential to produce multiple adverse effects presenting the dermatologist with difficult decisions in the management of patients with potentially steroid responsive disorders. This article reviews the side effects of systemic corticosteroids, comments on strategies to minimize these side effects, as well as, outlining suggested mechanisms by which physicians may minimize the risks of medical legal consequences owing to adverse reactions to these drugs.

Administration, Oral↗
PubMed1998

Quantifying the costs of serious adverse drug reactions to antiepileptic drugs.

PURPOSE: We assessed from an institutional perspective the direct costs of severe adverse cutaneous or hypersensitivity reactions due to antiepileptic drug (AED) therapy that led to hospitalization or prolonged hospital stay. METHODS: Patients admitted for or developing severe AED-induced cutaneous or hypersensitivity reactions while in hospital from January 1990 through June 1996 were identified by ICD-9 codes E936, E937, E693, E695.1, E995.1, and E995.2. Identified cases were analyzed retrospectively by chart review and were included in the analysis if a causal relationship was determined to be possible, probable, or definite. Clinical outcomes were abstracted and related direct costs of the adverse drug reactions (ADRs) calculated. RESULTS: A total of 384 cases were identified by ICD-9 codes, of which 13 cases (mean age +/- SD 52.9+/-21.0 years) were included for further analysis. Eight patients (62%) were admitted because of an ADR (median length of stay 9.5 days; range 4-43), five (38%) experienced an ADR during hospitalization (median duration of ADR episodes 8.5 days; range: 7-21 days). The median direct medical costs of the ADRs were Canadian (CDN) $3,128 (range 1,149-21,293) per patient. CONCLUSIONS: The management of serious cutaneous and hypersensitivity ADRs due to AEDs is associated with considerable direct medical costs. These figures should be considered along with drug acquisition costs and treatment of clinical successes and failures in the overall assessment of the economic impact of pharmacotherapy. Prospective collection of direct costs associated with ADRs in clinical trials would be of value.

Adolescent↗
PubMed1998

Gender differences in adverse drug reactions.

The objective of this study is to identify gender-related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were female. The mean age of the patients was 43 +/- 17 years. Drug classes most frequently reported to elicit an adverse event were general antiinfectives (60.4%), nervous system agents (21.5%), and musculoskeletal agents (3.7%). Skin-related reactions accounted for 49.0% of all reported adverse drug reactions. More than one agent was reported to be responsible for the adverse drug reaction(s) in 50% of the female patients, versus 33.1% of all male patients. Of the female patients, 47.6% were referred for skin or oral challenge testing, versus 41.6% of the male patients. Of the female patients, 6.2% tested positive to the agent compared with 6.1% of all male patients. These results support previous findings that female gender is a risk factor for the development of adverse drug reactions. Further work is required to elucidate the mechanisms explaining the differences observed between male and female patients.

Administration, Oral↗
PubMed1998

Lamotrigine-associated anticonvulsant hypersensitivity syndrome.

We systematically reviewed and analyzed published and unpublished cases of lamotrigine-associated adverse drug reactions consistent with the features of the anticonvulsant hypersensitivity syndrome (AHS) to identify characteristics of the syndrome. We identified 26 cases (mean age, 28+/-18 years; range, 3.5 to 74 years; 54% female), of which nine were published. The characteristics of the syndrome associated with lamotrigine are comparable to AHS induced by older aromatic anticonvulsants.

Adolescent↗
PubMed1997

Terbinafine therapy may be associated with the development of psoriasis de novo or its exacerbation: four case reports and a review of drug-induced psoriasis.

Adverse effects may occur in 10.4% of patients receiving terbinafine therapy, with cutaneous reactions in 2.7%. We describe the development of psoriasis in four patients who took oral terbinafine. Two patients had plaque-type psoriasis that flared 12 and 17 days, respectively, after starting terbinafine. Another patient developed pustular-type psoriasis de novo after 27 days of terbinafine therapy. The fourth patient was a psoriatic with stable plaque disease who experienced a pustular flare after taking terbinafine for 21 days. We are aware of only one report in the literature in which a patient developed pustular psoriasis de novo after 5 days of terbinafine therapy. In all patients the psoriasis cleared or lessened after discontinuation of terbinafine and institution of antipsoriatic therapy.

Adult↗
PubMed1997

Pancreatic insufficiency due to antituberculous therapy.

OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.

Antitubercular Agents↗
PubMed1997

Comparative safety of tetracycline, minocycline, and doxycycline.

BACKGROUND: Because minocycline can cause serious adverse events including hypersensitivity syndrome reaction (HSR), serum sicknesslike reaction (SSLR), and drug-induced lupus, a follow-up study based on a retrospective review of our Drug Safety Clinic and the Health Protection Branch databases and a literature review was conducted to determine if similar rare events are associated with tetracycline and doxycycline. Cases of isolated single organ dysfunction (SOD) attributable to the use of these antibiotics also were identified. OBSERVATIONS: Nineteen cases of HSR due to minocycline, 2 due to tetracycline, and 1 due to doxycycline were identified. Eleven cases of SSLR due to minocycline, 3 due to tetracycline, and 2 due to doxycycline were identified. All 33 cases of drug-induced lupus were attributable to minocycline. Forty cases of SOD from minocycline, 37 cases from tetracycline, and 6 from doxycycline were detected. Hypersensitivity syndrome reaction, SSLR, and SOD occur on average within 4 weeks of therapy, whereas minocycline-induced lupus occurs on average 2 years after the initiation of therapy. CONCLUSIONS: Early serious events occurring during the course of tetracycline antibiotic treatment include HSR, SSLR, and SOD. Drug-induced lupus, which occurs late in the course of therapy, is reported only with minocycline. We theorize that minocycline metabolism may account for the increased frequency of serious adverse events with this drug.

Adolescent↗
PubMed1996

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports.

OBJECTIVE: To review reported cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the use of selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES: A search of MEDLINE for reports of hyponatremia and SIADH associated with the use of fluoxetine, fluvoxamine, paroxetine or sertraline published between January 1980 and May 1995. Unpublished reports of cases were requested from the pharmaceutical industry, the Ontario Medical Association, the Health Protection Branch of Health Canada, the US Food and Drug Administration and the World Health Organization. DATA SELECTION AND EXTRACTION: Spontaneous reports from postmarketing surveillance. DATA SYNTHESIS: A total of 736 cases of hyponatremia [corrected] and SIADH associated with SSRI use were reported. Fluoxetine was involved in 554 (75.3%) of the cases, paroxetine in 91 (12.4%), sertraline in 86 (11.7%) and fluvoxamine in 11 (1.5%). Reports of 30 cases were published. The remaining 706 cases were reported to monitoring bodies and the pharmaceutical industry. According to information in the published reports, the median time to onset of hyponatremia was 13 days (range 3 to 120 days). Most (83%) of the published cases involved patients 65 years of age or more, as compared with 74% of the unpublished cases. CONCLUSION: Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.

1-Naphthylamine↗