Clin Pharmacokinet
-
Recent clinical investigations and reports of theoretical models have provided considerable insight into mechanisms of hepatic drug elimination and into derangements that may occur in drug absorption and disposition in patients with hepatic disease. Carefully conducted and well controlled clinical studies have demonstrated that hepatic disease may alter substantially one or more pharmacokinetic parameters of drug absorption and disposition. Physiological models of hepatic drug elimination have emphasised the importance of physiological variables such as hepatic blood flow, protein binding and intrinsic clearance of the liver on hepatic drug elimination. ⋯ Although general guidelines may be formulated now to assist clinicians in constructing dosage regimens of several important drug classes (notably the benzodiazepines and barbiturates) in hepatic disease, it is not now possible to predict in an individual the influence of a specific hepatic disease on the disposition of a drug, with the exception that the oral availability of drugs with high hepatic extraction ratios is increased in patients with cirrhosis and protacaval shunting of blood. Attempts to correlate concentrations of endogenous substances (such as bilirubin), or the pharmacokinetics of model drugs (such as antipyrine), with the pharmacokinetics of drugs that are useful in patients with hepatic impairment have not resulted in clinically useful tests of hepatic drug elimination. Following the administration of a drug to a patient with hepatic impairment, careful monitoring of the patient and also monitoring of plasma or blood drug concentrations remain important considerations.
-
The introduction of the new long acting local anaesthetics, bupivacaine and etidocaine, has stimulated an expansion of interest in regional anaesthesia, particularly for obstetrical applications and pain therapy. System toxicity following injection of local anesthetics occurs albeit infrequently, and tentative correlations have been made between the onset of CNS and cardiovascular effects and circulating drug concentrations in both adults and neonates. Amongst other factors, interpretation of these relationships depends upon blood distribution and plasma binding of the agents, sampling sites and acid-base balance. The disposition kinetics and placental transfer of the amide type agents have been well characterised. ⋯ The time course of local anaesthetic remaining at the site of injection has been calculated following intravenous regional anaesthesia and peridural block. This has allowed prediction of the local and systemic accumulation of the drugs following contined dosage. Blood concentrations of local anaesthetics after perineural injection are not closely related to age, weight or pregnancy but may be influenced by diseases associated with haemodynamic changes and by other drugs given at or around the time of regional blockade.
-
Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. ⋯ It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity.
-
The elderly are generally considered to be different from young people in terms of drug response and this applies particularly to quantitative differences. While altered drug handling is a major potential source of difference in responsiveness to drugs, the relative contribution of pharmacokinetics and pharmacodynamics to this difference is not clear. In the present review we have examined the available data on pharmacokinetics in the elderly. ⋯ Drug clearance comparisons between old and young have been carried out for only three renally excreted drugs-digoxin, propicillin and sulphamethizole. With digoxine and sulphamethizole, the evidence is that renal excretion is diminished in the elderly. With propicillin, changes in volume of distribution predominate, resulting in higher plasma levels in the elderly but similar percent recovery in urine...