Phospholipidosis

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Phospholipidosis is a lipid storage disorder in which excess phospholipids accumulate within cells.

Drug-induced phospholipidosis is an adverse drug reaction that occurs with many cationic ampiphillic drugs. While the mechanism is not truly understood, three possible mechanisms have been propsed. One possibility is the drugs inhibits phospholipases, rendering the cell unable to break down excess phospholipids. Another possible mechanism is the increased synthesis of phospholipids within the cell. A third possibility is the binding of drug to phospholipids, which would cause the phospholipases to be unable to break down these drug-phospholipid dimers. A build-up of these phospholipids bound to drug would cause an almost drug-depot, with the possibility of decreased metabolism of drug, a later increase in exposure as drug is release from the depot, or a disruption in cell function due to the cytoplasmic space the phospholid accumulation takes up. A major concern for the regulatory agencies is drug-induced phospholipidosis occurring in neurons, since this could disrupt cell-to-cell signaling.