| Popis: |
Summary A major reason for clinical variations between opioids is differences in their physicochemical and pharmacokinetic properties. Important factors are p K a , lipid solubility and protein binding. Opioids are basic drugs that, with the exception of alfentanil, have p K a values greater than 7.4, so that the ionized form of the drug predominates in the blood. The p K a of alfentanil is 6.5 so that 90% of alfentanil is non-ionized at pH 7.4. This facilitates its access into the CNS. p K a is also an important determinant of absorption from the gastrointestinal tract. Opioid pharmacokinetics are also affected by changes in blood and tissue pH (e.g. during respiratory alkalosis). While morphine is mainly bound to albumin, the most important binding protein for the fentanyl analogues is α 1 -acid glycoprotein (AAG). Change in the concentration of this protein can affect opioid pharmacodynamics, and has special relevance during pregnancy and in the newborn. Because of immaturity of the cytochrome P-450 isoenzyme system, neonates metabolize opioids much less efficiently than older children or adults. Generally the pharmacokinetics of an opioid are similar in children and in young adults, although often clearance is greater in young children. In elderly patients the influence of age on opioid pharmacokinetics is less well defined and many of the clinical differences between young and elderly patients in their responses to opioids may be due to pharmacodynamic differences or attributable to concomitant diseases or medication. The pharmacokinetics of these drugs are also influenced by renal and hepatic disease, although the extent is very drug dependent. The elimination of morphine metabolites is especially affected by decreases in renal filtration. Not surprisingly, cardiac surgery with cardiopulmonary bypass markedly affects opioid pharmacokinetics. Apart from changes in distribution volume and hepatic clearance, sequestration of opioids on to the extracorporeal circuit may be important for some opioids. Significant uptake of opioids by the lungs has also been demonstrated. |
