Agranulocytosis propylthiouracil

Agranulocytosis is potentially the most serious adverse reaction to methimazole and propylthiouracil. The nurse notifies the primary health care provider if fever, sore throat, rash, headache, hay fever, yellow discoloration of the skin, or vomiting occurs. 

Thiono and sulfhydryl drugs are also associated with a significant incidence of a lupus-like syndrome. Propylthiouracil is associated with a significant incidence of lupus [18] as well as liver toxicity [19, 20] and agranulocytosis [21], Penicillamine is associated with lupus, agranulocytosis [22] and a variety of autoimmune syndromes as discussed later. 

Guffy, M.M., Goeken, N.E., and Burns, C.P., Granulocytotoxic antibodies in a patient with propylthiouracil-induced agranulocytosis, Arch. Intern. Med., 144, 1687, 1984. 

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. 

Propylthiouracil (PTU) Inhibit thyroid peroxidase reactions block iodine organification inhibit peripheral deiodination of T4 and T Hyperthyroidism Oral duration of action 6-8 h delayed onset of action Toxicity Nausea, gastrointestinal distress, rash, agranulocytosis, hepatitis,hypothyroidism... 

Beebe RT, Propp S, McClintock JC, Versaci A. Fatal agranulocytosis during treatment of toxic goiter with propylthiouracil. Ann Intern Med 1951 34(4) 1035-40. 

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. 

Patients should therefore be warned to seek immediate medical help if a fever or sore throat develops during antithyroid drug treatment. If the drug is withdrawn immediately recovery is the rule, but fatal cases have also been reported (20,21). In one case agranulocytosis unusually occurred after a second exposure to the drug, in this case propylthiouracil (22). 

Toth AL, Mant MJ, Shivji S, et al. Propylthiouracil-induced agranulocytosis An unusual presentation and a possible mechanism. Am J Med 1988 85 725-727. 

Experiments with cats showed that propylthiouracil induces systemic lupus erythematosus-like phenomena (autoantibodies against nuclear antigen, Smith [Sm] antigen, red blood cells, and cytoplasmic components, lymphoadenopathy, weight loss) (Aucoin, 1989). However, important propylthiouracil-induced symptoms, such as agranulocytosis and liver toxicity, observed in humans are... 

Waldhauser L, Uetrecht J. Oxidation of propylthiouracil to reactive metabolites by activated neutrophils. Implications for agranulocytosis. Drug Metab Dispos 1991 19 354-359. 

Concomitant use with propylthiouracil increases the risk of agranulocytosis concomitant use with lithium may result in severe neurologic toxicity with an encephaUtis-like syndrome, and in decreased therapeutic response to prochlorperazine. 

Antithyroid drugs include iodide (discussed above) and the thioamides. The principal thioamides are propylthiouracil and methimazole. Almost all patients respond to these agents. However, immunologic complications are not rare. Skin rashes are the most common. Agranulocytosis, cholestatic jaundice, hepatocellular damage, and exfoliative dermatitis are uncom-... 

Propylthiouracil is usually reserved for patients intolerant to car-biina/ole. It i.s associated with a higher incidence of agranulocytosis (0.4 Jf ) than carbimuzolc (0.1 %), In addition to inhibiting hormone synthesis. propylthiouracil also inhibits the peripheral dciodination of T4 and perhaps has an immunosuppres.sive action. 

Some new cases of bone marrow depression, a well-known side effect (SED VIII), have been reported (9, 10 ). In 3 cases of acute agranulocytosis (2 secondary to methi-mazole and 1 secondary to propylthiouracil)... 

The frequency of haematological side effects of antithyroid drugs was estimated from questionnaires sent to members of the Philadelphia Endocrine Society 0.6% of 2015 patients developed agranulocytosis during treatment with methimazole compared to 1.8% of 1140 patients treated with propylthiouracil. The frequency of aplastic anaemia was low, only one case being reported in each series (11 ). 

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