Adverse drug reactions agranulocytosis

Anonymous. Mianserin a possible cause of neutropenia and agranulocytosis. Adverse Drug Reactions Advisory Committee. Med J Aust I980 2(T2) 673A. 

Yang L, Wang K, Chen J et al (2011) Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome-clozapine-induced agranulocytosis as a case study. PLoS ComputBiol 7 el002016. doi 10.1371/journal.pcbi.1002016... 

Communication issued by the Netherlands national centre for monitoring of adverse drug reactions (1976) Agranulocytosis during treatment with aprindine. Ned. T. Ceneesk., in press. 

The most serious adverse reaction associated with these drugs is agranulocytosis (decrease in the number of white blood cells [eg, neutrophils, basophils, and eosinophils]). Reactions observed with agranulocytosis include hay fever, sore throat, skin rash, fever, or headache Other major reactions include exfoliative dermatitis, granulocytopenia, aplastic anemia, hypoprothrombinemia, and hepatitis. Minor reactions, such as nausea, vomiting, and paresthesias, also may be seen. 

Adverse effects occur in 3-12% in the form of rash, fever, urticaria, vasculitis, arthralgia, a lupuslike reaction, cholestatic jaundice, hepatitis, lym-phadenopathy and polyserositis but the most dangerous adverse effect is agranulocytosis (it occurs only in 0.3-0.6%). The reaction is readily reversible when the drug is discontinued. Cross-sensitivity between propylthiouracil and methimazole is about 50%, therefore switching drugs in patients with severe reactions is not recommended. 

Perhaps one of the most common side effects is a benign transient leukopenia characterized by a white blood cell (WBC) count of less than 4000/mm. This condition occurs in up to 12% of adults and 25% of children, and sometimes can be confused with mild leukopenia seen in Graves disease. This mild leukopenia is not a harbinger of the more serious adverse effect of agranulocytosis, so therapy can usually be continued. If a minor adverse reaction occurs with one antithyroid drug, the alternate thiourea may be tried, but cross-sensitivity occurs in about 50% of patients. ... 

By most reports, idiosyncratic drug-induced hematologic disorders are rare. Relatively few epidemiologic studies have addressed the actual incidence of these adverse reactions. A report from The Netherlands estimated the incidence of drug-associated agranulocytosis as 1.6 to 2.5 cases per million inhabitants per year. Similar results were found in epidemiologic studies conducted in Thailand and BraziU Older data from a study conducted in Europe and Israel estimated the incidences of aplastic anemia and agranulocytosis to be 0.5 and 3.1 cases per million per year, respectively. ... 

Agranulocytosis Because of a significant risk of agranulocytosis, a potentially life-threatening adverse reaction, reserve clozapine for use in the treatment of severely ill schizophrenic patients who fail to show an acceptable response to adequate courses of standard antipsychotic drug treatment because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with clozapine, it... 

Amodiaquine (Camoquin) is another 4-aminoquinoline derivative whose antimalarial spectrum and adverse reactions are similar to those of chloroquine, although chloroquine-resistant parasites may not be amodi-aquine-resistant to the same degree. Prolonged treatment with amodiaquine may result in pigmentation of the palate, nail beds, and skin. There is a 1 2000 risk of agranulocytosis and hepatocellular dysfunction when the drug is used prophylactically. 

Adverse effects include haemolysis which is most common and dose related. Patients with G-6-PD deficiency are more susceptible. Nausea, vomiting, anorexia, headache, methaemoglobinaemia, drug fever, allergic skin reactions, insorrmia and paresthesia. Rarely hepatitis and agranulocytosis. 

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug therapy and the underlying heart disease appears important. 

Among the more severe adverse reactions, Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, and nephrotic syndrome have all been observed. Like diclofenac, sulindac may have some propensity to cause elevation of serum aminotransferases it is also sometimes associated with cholestatic liver damage, which disappears when the drug is stopped. 

Blood dyscrasias, mostly dose independent, are among the most important allergic-type adverse reactions to drugs. Aplastic anemia is a serious but rare (presumably) idiosyncratic reaction. It has been reported in association with chloramphenicol, quinacrine, phenylbutazone, mephenytoin, gold compounds, and potassium chlorate. Hemolytic anemia, thrombocytopenia, and agranulocytosis may result from an unusual, acquired sensitivity to a variety of widely used drugs including aminopyrine, phenylbutazone, phenothiazines, propylthiouracil, diphenylhydantoin, penicillins, chloramphenicol, sulfisoxazole, and tolbutamide. 

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