Drug-Induced Blood Dyscrasias

Categories of undesirable effects of drugs are described. Recent experiments on the production of hypersensitization (1) by the use of ECT solution to enhance skin sensitization to penicillin, (2) through the activity of common metabolites of different drugs, and (3) to a non-sensitizing drug by pretreatment with a sensitizing agent are reviewed. The mechanism of hemolytic anemia due to an inherited enzymatic defect and that of drug-induced purpura and the agranulocytic agents is discussed. The three groups of drugs—(1) rarely toxic, e.g. quinine; (2) always toxic in sufficient amounts, e.g. nitrogen mustard; (3) intermediate, e.g. chloramphenicol—are presented, with special consideration of chloramphenicol. It is the responsibility of the pharmacologist to develop and adopt newer methods for toxicity detection, and of the clinician to practise caution in prescribing drugs and to attempt the early recognition of any disorder they may induce. The incidence, diagnosis, prevention, treatment and prognosis of the drug-induced dyscrasias are discussed.     

Drug-induced phospholipidosis

Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. Organs affected by phospholipidosis exhibit inflammatory reactions and histopathological changes. Despite significant advances in the understanding of drug-altered lipid metabolism, the relationship between impaired phospholipid metabolism and drug-induced toxicity remains enigmatic. Here we review molecular features of inheritable lysosomal storage disorders as a molecular mimicry of drug-induced phospholipidosis for an improved understanding of adverse drug reaction.     

Drug-induced apoptosis in yeast

In order to alter the impact of diseases on human society, drug development has been one of the most invested research fields. Nowadays, cancer and infectious diseases are leading targets for the design of effective drugs, in which the primary mechanism of action relies on the modulation of programmed cell death (PCD). Due to the high degree of conservation of basic cellular processes between yeast and higher eukaryotes, and to the existence of an ancestral PCD machinery in yeast, yeasts are an attractive tool for the study of affected pathways that give insights into the mode of action of both antitumour and antifungal drugs. Therefore, we covered some of the leading reports on drug-induced apoptosis in yeast, revealing that in common with mammalian cells, antitumour drugs induce apoptosis through reactive oxygen species (ROS) generation and altered mitochondrial functions. The evidence presented suggests that yeasts may be a powerful model for the screening/development of PCD-directed drugs, overcoming the problem of cellular specificity in the design of antitumour drugs, but also enabling the design of efficient antifungal drugs, targeted to fungal-specific apoptotic regulators that do not have major consequences for human cells.     

Drug-induced anemias

The facts known today about the occurrence and possible mechanisms of anaemias caused by medicaments are represented in a survey. In this connection toxic haemolytic anaemias, immunohaemolytic anaemias, toxic aplastic anaemias, megaloblastic anaemias, and some other, more rarely occurring types are referred to.     

Drug-induced urinary calculi

Urinary calculi may be induced by a number of medications used to treat a variety of conditions. These medications may lead to metabolic abnormalities that facilitate the formation of stones. Drugs that induce metabolic calculi include loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused. Correcting the metabolic abnormality may eliminate or dramatically attenuate stone activity. Urinary calculi can also be induced by medications when the drugs crystallize and become the primary component of the stones. In this case, urinary supersaturation of the agent may promote formation of the calculi. Drugs that induce calculi via this process include magnesium trisilicate; ciprofloxacin; sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination with guaifenesin. When this situation occurs, discontinuation of the medication is usually necessary.