Delayed drug reactions

Considering the magnitude of the problem of delayed hypersensitivity reactions to drugs and the difficulties associated wifli flie lymphocyte transformation test, there is a need to develop sensitive and specific tests that are more easily and quickly carried out, widely apphcable to flie many forms of delayed drug reactions and valuable for use in the clinic as well as the research laboratory. 

In vitro tests for delayed drug reactions include the lymphocyte transformation test and local lymph node assay but nonproliferation-based in vitro assays of cell surface activation markers, cytokines, chemokines, and skin-homing receptors will be increasingly applied. 

Pichler WJ Delayed drug hypersensitivity reactions. Ann Intern Med 2003 139 683-693. 

Treatment regimens for intraabdominal infection can be judged as successful if the patient recovers from the infection without recurrent peritonitis or intraabdominal abscess and without the need for additional antimicrobials. A regimen can be considered unsuccessful if a significant adverse drug reaction occurs, reoperation or percutaneous drainage is necessary, or patient improvement is delayed beyond 1 or 2 weeks. 

Approximately 30-40% of patients will not respond to a given antidepressant and 60-75% may fail to achieve complete remission [16]. Consequently, in its least restricted definition, treatment resistance could be detected in the majority of depressed patients under treatment. Moreover, prior treatment failure negatively influences the response to subsequent antidepressant treatment, decreasing the odds of treatment response by a factor of 15-20% for each failed treatment [17]. The delayed onset of symptom relief (which takes three to eight weeks to occur) and the presence of adverse drug reactions contribute significantly to low treatment compliance. 

Although the tricyclic and MAOI antidepressants cause an immediate pharmacologic action (drug reaction in the body), their clinical action (observable reaction) is delayed. This delay can last weeks or even months. This makes it difficult to use these antidepressants to treat severe depression when an immediate response is desired. The more severe cases of depression and other psychiatric and emotional problems may require other treatments in addition to the drug therapy. 

An antibody directed at the murine epitope of infliximab may develop in patients. A delayed infusion reaction, which occurs 1-2 weeks after infusion, develops in approximately 5% patients who are re-treated with infliximab. Delayed infusion reaction is more common in patients with circulating anti-infliximab antibodies (20-30% of those getting multiple infusions) than in those without the antibodies. These reactions consist of myalgia arthralgia fever rash urticaria and facial, hand, and lip edema. Delayed reactions respond to symptomatic treatment with antihistamines or corticosteroids. Positive antinuclear antibodies (ANA) and anti-dsDNA develop in a small number of patients. Development of a lupus-like syndrome has been reported that resolved after discontinuation of the drug. 

C.J. Davies, et al., Delayed adverse reactions to drugs used in anaesthesia. Adv. Drug React. Bull. 647-650, April 1995. 

Immunologic Complications of infusion, drug-induced lupus erythematosus, delayed hypersensitivity reaction... 

In the absence of additional reports of long-range consequences In subjects who had received the anticholinergic test compounds, data have been sought on delayed adverse reactions to other anticholinergic drugs used therapeutically, such as Oltran and atropine. 

The Federal Institute of Drugs and Medical Devices in Germany has surveyed a total of 1135 adverse drug reactions (acute and late) associated with iotrolan 280 and 1354 reports associated with iodixanol at various iodine concentrations (31). There were late adverse reactions (observed later than 1 hour after injection) in 757 cases (67%) associated with iotrolan 280, and in 525 cases (39%) associated with iodixanol. Late reactions were observed mainly in the first 24 hours, with occasional reports at 24-72 hours after injection. Rarely, delayed contrast reactions have been... 

Walchner M, Rueff F, Przybilla B. Delayed-type hypersensitivity to mofebutazone underlying a severe drug reaction. Contact Dermatitis 1997 36(l) 54-5. 

Calkin JM, Maibach HI. Delayed hypersensitivity drug reactions diagnosed by patch testing. Contact Dermatitis 1993 29(5) 223-33. 

The selection of appropriate antipsychotic treatment is often a trial-and-error procedure, with multiple failed trials required before achieving an acceptable balance between symptom management and tolerability of adverse effects. This is problematic because it increases the risk of adverse drug reactions and delays symptom management, worsening long-term treatment outcomes [2]. 

The precise mechanisms of many drug reactions are not known, although the reactions are believed to be immune mediated. Perhaps most common are the delayed dermatologic reactions that occur with a variety of drugs (especially penicillins and sulfonamides). These reactions may be evident as macropapular, morbilliform, or erythematous rashes exfoliative dermatitis photosensitivity reactions or eczema. These reactions also may be manifest as pruritus, urticaria, and angioedema. 

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