Adverse Drug Effects: A Nursing Concern

Pharmacokinetic effects – absorption and distribution 19sequestered. Due to the relatively low blood flow through fatty tissue,it becomes a stable reservoir for the drug.Body fat is not the only tissue in which drugs can accumulate. Asa result of specialized transport mechanisms iodine is concentratedin the thyroid gland. The affinity of iodine for thyroid tissue is sostrong that radioactive iodine can be given orally, and it will concentrateto such an extent in the thyroid that it can be utilized to destroya malignancy of the gland without causing significant radiationdamage elsewhere in the body. Other examples of tissue bindinginclude the phenothiazines and chloroquine that bind to melanincontainingtissues, including the retina, which may explain theirability to cause retinopathy, and the tetracyclines which bind togrowing bones and teeth resulting in mottling of the teeth andincreased bone fragility in children.Carrier-mediated transportCell membranes frequently contain carrier molecules, i.e. transmembraneproteins, which bind to a specific particle and move it tothe other side of the membrane. These transporters can act passivelyand move particles along their concentration gradient, in a processtermed facilitated diffusion. Alternatively the carrier may be coupledto an energy source and so can move the particle across themembrane against its concentration gradient. Drugs can utilizethese carriers for distribution purposes and important sites for thisprocess are the gastrointestinal tract, the biliary tract, the renaltubule and the blood-brain barrier. For example, in the gut,levodopa, which is used to treat Parkinson’s disease, is taken up by acarrier that normally transports phenylalanine, while the cytotoxicdrug fluorouracil is transported by the system that carries the naturalpyrimidines, i.e. thymine and uracil (Rang et al., 1995).Barriers to drug distributionSome of the membranes in the body can act as barriers to drugdistribution. Two examples of this are the blood-brain barrier andthe placental barrier (see p 67 for the latter).Blood-borne substances within the capillaries of the brain areseparated from the interstitial space and nerve cells by a continuouslayer of endothelial cells. These cells are joined by tight junctions, are