Drug Hypersensitivity: Immunologically mediated adverse reactions to medicinal substances used legally or illegally.Drug Hypersensitivity Syndrome: Severe drug eruption characterized by high fever, erythematous rash and inflammation of internal organ(s).Drug Eruptions: Adverse cutaneous reactions caused by ingestion, parenteral use, or local application of a drug. These may assume various morphologic patterns and produce various types of lesions.Stevens-Johnson Syndrome: Rare cutaneous eruption characterized by extensive KERATINOCYTE apoptosis resulting in skin detachment with mucosal involvement. It is often provoked by the use of drugs (e.g., antibiotics and anticonvulsants) or associated with PNEUMONIA, MYCOPLASMA. It is considered a continuum of Toxic Epidermal Necrolysis.Drug-Related Side Effects and Adverse Reactions: Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.HLA-B Antigens: Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Syndrome: A characteristic symptom complex.Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.Alveolitis, Extrinsic Allergic: A common interstitial lung disease caused by hypersensitivity reactions of PULMONARY ALVEOLI after inhalation of and sensitization to environmental antigens of microbial, animal, or chemical sources. The disease is characterized by lymphocytic alveolitis and granulomatous pneumonitis.New Zealand: A group of islands in the southwest Pacific. Its capital is Wellington. It was discovered by the Dutch explorer Abel Tasman in 1642 and circumnavigated by Cook in 1769. Colonized in 1840 by the New Zealand Company, it became a British crown colony in 1840 until 1907 when colonial status was terminated. New Zealand is a partly anglicized form of the original Dutch name Nieuw Zeeland, new sea land, possibly with reference to the Dutch province of Zeeland. (From Webster's New Geographical Dictionary, 1988, p842 & Room, Brewer's Dictionary of Names, 1992, p378)Eosinophilia: Abnormal increase of EOSINOPHILS in the blood, tissues or organs.Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes.Dideoxynucleosides: Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.Organic Anion Transport Protein 1: A polyspecific transporter for organic cations found primarily in the kidney. It mediates the coupled exchange of alpha-ketoglutarate with organic ions such as P-AMINOHIPPURIC ACID.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Doxycycline: A synthetic tetracycline derivative with similar antimicrobial activity.Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.Diet, Mediterranean: A diet typical of the Mediterranean region characterized by a pattern high in fruits and vegetables, EDIBLE GRAIN and bread, potatoes, poultry, beans, nuts, olive oil and fish while low in red meat and dairy and moderate in alcohol consumption.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Spain: Parliamentary democracy located between France on the northeast and Portugual on the west and bordered by the Atlantic Ocean and the Mediterranean Sea.Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.Roseolovirus Infections: Infection with ROSEOLOVIRUS, the most common in humans being EXANTHEMA SUBITUM, a benign disease of infants and young children.Herpesvirus 6, Human: The type species of ROSEOLOVIRUS isolated from patients with AIDS and other LYMPHOPROLIFERATIVE DISORDERS. It infects and replicates in fresh and established lines of hematopoietic cells and cells of neural origin. It also appears to alter NK cell activity. HHV-6; (HBLV) antibodies are elevated in patients with AIDS, Sjogren's syndrome, sarcoidosis, chronic fatigue syndrome, and certain malignancies. HHV-6 is the cause of EXANTHEMA SUBITUM and has been implicated in encephalitis.Exanthema Subitum: An acute, short-lived, viral disease of infants and young children characterized by a high fever at onset that drops to normal after 3-4 days and the concomitant appearance of a macular or maculopapular rash that appears first on the trunk and then spreads to other areas. It is the sixth of the classical exanthematous diseases and is caused by HHV-6; (HERPESVIRUS 6, HUMAN). (From Dorland, 27th ed)Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.Strophanthins: A number of different cardioactive glycosides obtained from Strophanthus species. OUABAIN is from S. gratus and CYMARINE from S. kombe. They are used like the digitalis glycosides.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Vasoplegia: Condition of low SYSTEMIC VASCULAR RESISTANCE that develops secondary to other conditions such as ANAPHYLAXIS; SEPSIS; SURGICAL SHOCK; and SEPTIC SHOCK. Vasoplegia that develops during or post surgery (e.g., CARDIOPULMONARY BYPASS) is called postoperative vasoplegic syndrome or vasoplegic syndrome.Antitussive Agents: Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally.Cough: A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs.Proton Pump Inhibitors: Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.Pharmacies: Facilities for the preparation and dispensing of drugs.Pharmacy Service, Hospital: Hospital department responsible for the receiving, storing, and distribution of pharmaceutical supplies.Diving: An activity in which the organism plunges into water. It includes scuba and bell diving. Diving as natural behavior of animals goes here, as well as diving in decompression experiments with humans or animals.Pulmonary Eosinophilia: A condition characterized by infiltration of the lung with EOSINOPHILS due to inflammation or other disease processes. Major eosinophilic lung diseases are the eosinophilic pneumonias caused by infections, allergens, or toxic agents.Scleroderma, Systemic: A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.Life Expectancy: Based on known statistical data, the number of years which any person of a given age may reasonably expected to live.Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Receptors, Antigen, T-Cell, alpha-beta: T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.Exanthema: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.

Various forms of chemically induced liver injury and their detection by diagnostic procedures. (1/1024)

A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberation of the host permitting the accumulation of hepatotoxic metabolites. The syndromes of hepatic disease produced by drugs have been classified hepatocellular, hepatocanalicular, mixed and canalicular. Measurement of serum enzyme activities has provided a powerful tool for studies of hepatotoxicity. Their measurement requires awareness of relative specificity, knowledge of the mechanisms involved, and knowledge of the relationship between known hepatotoxic states and elevated enzyme activities.  (+info)

Glomerular, tubular and interstitial nephritis associated with non-steroidal antiinflammatory drugs. Evidence of a common mechanism. (2/1024)

AIMS: To study the mechanisms behind NSAID-associated nephropathy. METHODS: Analysis of published case reports satisfying strict criteria for NSAID nephropathy. RESULTS: Ninety-seven cases with acute nephritis (AN; 19 patients), minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN; 19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis subgroups (8 patients) were identified. Hypersensitivity reactions were seen in all groups, most often in AN. Proteinuria was more severe in MC and FS than in MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely associated with hypersensitivity, interstitial damage and renal failure. Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had discontinued NSAID treatment had improved, 57 with normal renal function. CONCLUSIONS: NSAID nephropathy may be caused by hypersensitivity. The reaction is milder than in drug-induced acute tubulointerstitial nephritis, probably because the offending drug inhibits the inflammatory reaction it has started itself. Heavy proteinuria is probably due to lymphokines produced as a result of the immunological response. If the allergic reaction is strong, AN is produced rapidly with severe renal failure but little proteinuria; if it is less violent, immunocompetent cells may develop to produce lymphokines and proteinuria. Immune complexes may be formed eventually, secondary to the increased glomerular permeability, more easily in patients with a hyperactive immune system and with little consequence for renal function.  (+info)

Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity. (3/1024)

1. Bioactivation of sulphamethoxazole (SMX) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity. We have therefore examined the cellular metabolism, disposition and conjugation of SMX and its metabolites in vitro. 2. Flow cytometry revealed binding of N-hydroxy (SMX-NHOH) and nitroso (SMX-NO) metabolites of SMX, but not of SMX itself, to the surface of viable white blood cells. Cellular haptenation by SMX-NO was reduced by exogenous glutathione (GSH). 3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine (CYS), GSH, human peripheral blood cells and plasma, suggesting that this is an important and ubiquitous bioinactivation mechanism. 4. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer, and to a lesser extent, in cells and plasma. 5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability, with SMX having no effect. Lymphocytes were significantly (P<0.05) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils. 6. Partitioning of SMX-NHOH into red blood cells was significantly (P<0.05) lower than with the hydroxylamine of dapsone. 7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism. If an imbalance exists, haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur, and may result in drug hypersensitivity.  (+info)

Evidence of anaphylaxy after alteplase infusion. (4/1024)

BACKGROUND AND PURPOSE: Although alteplase, a recombinant tissue plasminogen activator (tPA), is structurally identical to endogenous tPA and therefore should not induce allergy, single cases of acute hypersensitivity reactions have been reported. Until now, specific antibodies against alteplase were not detected in blood samples obtained in these patients. CASE DESCRIPTION: We report an anaphylactic reaction in a 70-year-old white female who was treated with intravenous alteplase for thrombolysis of acute ischemic stroke 160 minutes after onset of a right-sided hemiparesis. Thirty minutes after infusion of alteplase had been started, the patient suffered acute severe sinus tachycardia and hypotension, followed by cyanosis and loss of consciousness. The alteplase infusion was stopped, and following antiallergic therapy, tachycardia and hypotension resolved within 1 hour. The hemiparesis remained unaltered, but additional harm resulting from the hemodynamic complication was not observed. Serum samples analyzed with a radioimmunoprecipitation assay were negative for total antibodies to alteplase, but in a subsequent ELISA, both samples were positive for IgE antibodies to alteplase. CONCLUSIONS: The detection of specific IgE antibodies reactive with alteplase in this patient could provide the first evidence of an anaphylactic-type reaction to alteplase in man. Because previous exposure to alteplase can be excluded, the results suggest that this patient had preexisting antibodies that were cross-reactive with one or more epitopes of alteplase and therefore precipitated the anaphylactic-type reaction.  (+info)

Successful treatment with gabapentin in the presence of hypersensitivity syndrome to phenytoin and carbamazepine: a report of three cases. (5/1024)

We report three consecutive patients with hypersensitivity syndrome (HSS) due to phenytoin and carbamazepine and successful treatment with gabapentin. HSS is a rare but potentially fatal reaction to multiple drugs including several anticonvulsants. Cross-reactivity among drugs may occur. Immediate withdrawal of the offending drug is the most important step in treatment. Benzodiazepines acutely and, after resolution of the hepatitis, valproic acid have been successfully used for seizure control in patients with HSS. Our cases indicate that gabapentin is also a safe anticonvulsant in HSS.  (+info)

Highly Th2-skewed cytokine profile of beta-lactam-specific T cells from nonatopic subjects with adverse drug reactions. (6/1024)

A positive lymphocyte transformation test to beta-lactams (beta-L) was found in 12 of 29 subjects with adverse drug reaction (ADR) to beta-L, irrespective of either the type of clinical manifestation or the presence of specific serum IgE. Short-term T cell lines specific for penicillin G, amoxicillin, and ampicillin could be generated only from subjects with ADR (eight with positive and one with negative lymphocyte transformation test), while streptokinase and Dermatophagoides pteronyssinus group 1 (Der p 1)-specific T cells were obtained from all these subjects, from 7 atopic Der p-sensitive donors without history of ADR and 17 healthy nonatopic donors. Streptokinase-specific T cells from all subjects showed intracellular expression of IFN-gamma with poor or no IL-4, whereas Der p 1-specific T cells exhibited IFN-gamma but low or no IL-4 expression in nonatopics, and remarkable IL-4 expression in atopic donors. By contrast, all penicillin G-, ampicillin-, and amoxicillin-specific short-term T cell lines showed high intracellular expression of IL-4, IL-5, and IL-13, but poor or no expression of IFN-gamma, thus exhibiting a clear-cut Th2 profile. Accordingly, most penicillin G-specific T cell clones derived from two subjects with ADR released high concentrations of IL-4 alone or IL-4 and IFN-gamma. These data suggest that cytokines produced by Th2 cells play an important role in all beta-L-induced ADR, even when late clinical manifestations occur and an IgE-mediated mechanism is apparently indemonstrable.  (+info)

Prevention of occupational allergy caused by exposure to acid anhydrides. (7/1024)

This paper focuses on the prevention of IgE-mediated symptoms of the eyes and airways caused by exposure to acid anhydrides in the workplace. Acid anhydrides are widely used in the production of alkyd resins and as curing agents for epoxy resins. Heavy exposure to acid anhydrides causes severe irritation. However, reports of direct irritation of mucous membranes or skin are rare in recent years, since a package of multiple engineering controls has been introduced to reduce exposure. On the other hand, acid anhydrides are well-known industrial inhalant sensitizers and can cause occupational allergy even at very low exposure intensities. Therefore, safe use in industry demands both control of the level of exposure causing allergic diseases in the workshop and programmes for prevention of occupational allergy.  (+info)

20 years of medical surveillance on exposure to allergenic and non-allergenic platinum compounds: the importance of chemical speciation. (8/1024)

OBJECTIVES: Chloroplatinates are potent allergens but other soluble platinum compounds such as tetraammine platinum dichloride (TPC) do not provoke reactions in subjects who are sensitive to chloroplatinates. TPC has been used in the manufacture of autocatalysts for 20 years. This study analyses 20 year data on exposure to soluble platinum compounds and medical surveillance to confirm that TPC is not allergenic. METHODS: Workers in three distinct operations were exposed to soluble platinum compounds as chloroplatinates, chloroplatinates with TPC, or to TPC alone. Results of personal air sampling for soluble platinum compounds were compared together with the results of medical surveillance. RESULTS: The levels of exposure to soluble platinum compounds in each operation were comparable but the incidence of allergy was significantly different. In a subgroup of workers consistently exposed to chemical processes in each operation, the cumulative chance of being sensitised after 5 years of exposure was estimated as 51% for chloroplatinate exposure, 33% for mixed exposure, and 0% for TPC alone. The differences in sensitisation rates could not be explained by age, sex, and atopy. Nor could they be explained by the increased frequency of smoking in the workers with chloroplatinate exposure, despite the markedly higher risk of sensitisation in smokers. The differences could only be explained by the chemical stability of TPC. CONCLUSIONS: This study shows that the soluble platinum compound TPC is not allergenic under normal industrial conditions. Characterisation of the chemical compound (speciation) is essential to prevent stringent exposure limits being imposed for all soluble compounds on a generic basis.  (+info)

  • Although skin tests for lower molecular weight compounds such as sulphonamides are of questionable value, exceptions include the major antigenic determinant of penicillin (benzylpenicilloyl (BPO) compound) and some drugs used in general anaesthesia. (sheclick.com)
  • You may not be aware of your first exposure to a drug, however. (mayoclinic.org)
  • The time relationships may differ and prior drug exposure may be absent. (sheclick.com)
  • It is virtually impossible to react allergically on the first exposure to a drug never previously taken unless the patient has had a crossreacting drug or unknown subclinical exposure to the drug or related compounds such as meat tenderisers (chymopapain) or quaternary ammonium compounds in cosmetics (muscle relaxants). (sheclick.com)
  • Desensitization protocols are available to treat hypersensitivity reactions to most chemotherapy agents including taxenes, platinums, doxorubicin, monoclonal antibodies and others, by gradual re-introduction of small amounts of drug antigens up to full therapeutic doses. (qxmd.com)
  • Course Description Antibiotics are among the most frequently prescribed classes of drugs and it is estimated that approximately 50% of antibiotic use, in both the outpatient and inpatient settings, is inappropriate. (coursera.org)
  • Many drugs have "sulfa" components, including antimicrobial and non-antimicrobial agents. (wchcmr.org)
  • The enormous complexity of drug-hypersensitivity reactions is a consequence of the variety of mechanisms involved, which may be related, among others, to drug metabolism, generation of antigenic signals, stimulation and maturation of dendritic cells, presentation of haptens and mechanisms of cytotoxicity. (doabooks.org)