Hydralazine genetic factors

There are examples where several genetic factors, including the acetylator phenotype, operate together. Hydralazine toxicity is one such example, which is discussed in detail in chapter 7. Another is the hemolytic anemia caused by the drug thiozalsulfone (Promizole), which occurs particularly in those individuals who are both glucose-6-phosphate dehydrogenase deficient and slow acetylators. Promizole is acetylated, and studies in rapid and slow acetylator mice confirmed that acetylation was a factor as well as an extent of hydroxylation. The latter may also be another factor in humans as is discussed below. 

Hydralazine and isoniazid genetic factors in drug toxicity... 

The rate of drug metabolism, which is in part under genetic control, may be of importance. The population with low levels of hepatic acetyltransferase activity seems at greater risk of developing the hydralazine-induced lupus syndrome (Perry et al. 1970), but this does not hold for procainamide-induced lupus. Genetic factors have also been implied in pseudoallergic reactions, such as aspirin intolerance (Lockey et al. 1963). 

Environmental and genetic factors appear to influence the risk for ANCA-associated vasculitis (1). For example, sihca exposure appears to be a risk factor for ANCA-associated vasculitis (13,14). ANCA and ANCA-associated vasculitis can be induced by exposure to certain drugs, best documented for propylthiouracil and hydralazine (15-19). ANCAs are more frequent in patients treated with propylthiouracil, which is used to treat thyroid disease however, ANCAs are more frequent in patients with thyroid disease irrespective of treatment regimen (20), thus the respective roles of treatment for thyroid disease versus thyroid disease in risk for ANCA disease is difficult to discern. 

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