EFFECTS OF SURGERY ON THE PHARMACOKINETIC PARAMETERS OF DRUGS

As with other forms of stress, surgery is a time of fluctuating haemod ynamics, physiological shifts, intense metabolic changes, and protein catabolism and anabolism. At times, these changes can occur within hou rs. There is a reasonable body of literature concerning the adverse ef fects of surgery on gastric emptying, but not on the effects of surger y on the distribution, metabolism and excretion of drugs. Gastric empt ying is diminished or absent following major procedures, which prevent the delivery of orally administered drugs to their major site of abso rption, the small bowel. Changes in the paracellular absorption of dru gs may occur postoperatively, although transcellular absorption appear s to be unimpaired. Distribution is affected by changes in blood volum e, alterations in circulation, increases in the extracellular fluid an d changes in the circulating plasma protein levels, such as albumin an d al-acid glycoprotein. Little is known about alterations in drug meta bolism following surgery. However, it has been shown that systemic hyp oxia alters the function of some of the cytochrome P450 (CYP) system a nd increased levels of cytokines have an effect on the metabolism of a t least I drug. In addition, the renal elimination of drugs is affecte d in patients postoperatively, although the effects of biliary clearan ce in this period are difficult to determine. Despite the lack of rese arch into pharmacokinetics during the postoperative period, and given the immense and often sudden changes observed in patients post-surgery , it is reasonable to recommend vigilance with respect to drug therapy during this period.