Penicillin agranulocytosis with

Classic examples of Type B reactions are anaphylaxis with penicillins, hepatitis with halothane and agranulocytosis with clozapine. Additional categories of ADRs have also been suggested, as follows ... 

Hematologic/Lymphatic Anemia hemolytic anemia thrombocytopenia thrombocytopenic purpura eosinophilia leukopenia granulocytopenia neutropenia bone marrow depression agranulocytosis reduction of hemoglobin or hematocrit prolongation of bleeding and prothrombin time decrease in WBC and lymphocyte counts increase in lymphocytes, monocytes, basophils, and platelets. Hypersensitivity Adverse reactions (estimated incidence, 1% to 10%) are more likely to occur in individuals with previously demonstrated hypersensitivity. In penicillin-sensitive individuals with a history of allergy, asthma, or hay fever, the reactions may be immediate and severe. 

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. 

Imipenem caused positive dipstick tests for leukocytes in patients with agranulocytosis and normal urinary sediments. This phenomenon was reproducible in vitro with imipenem, meropenem, and clavulanic acid. Sulbactam, tazobactam, three penicillins, three cephalosporins, and the basic structures of penicillins, cephalosporins, and monobactams tested negative (50). 

This makes the blood cells antigenic and results in the production of IgG antibodies against them. The antibodies so produced activate the complement system. Complement destroys the blood cells. This can lead to haemolytic anaemia if red blood cells are involved and can occur in response to penicillin. If white blood cells are the target of the reaction then the result is agranulocytosis this can occur for example with carbimazole (used to treat an overactive thyroid gland, see Chapter 6). Thrombocytopenia can be the result if the cells involved are platelets this can happen in response to heparin (used in thrombotic disorders, see Chapter 4). 

Items 10-11 An immunosuppressed patient was treated for a bacterial infection with a parenteral penicillin. Within a few minutes of the penicillin injection, he developed severe bronchoconstriction, laryngeal edema, and hypotension. Due to the rapid administration of epinephrine, the patient survived. Unfortunately, a year later he was treated with an antipsychotic drug and developed agranulocytosis. 

Corcos JM, Soler-Bechara J, Mayer K, Freyberg RH, Goldstein R, Jaffe I (1964) Neutrophilic agranulocytosis during administration of penicillin. JAMA 189 265 Corran PH, Waley SJ (1975) The reaction of penicillin with proteins. Biochem J 149 357... 

---