Narcotic pharmacokinetics and dynamics: the basis of infusion applications

Abstract

Morphine, pethidine and fentanyl have similar pharmacokinetic profiles with moderately long elimination half-lives (3 to 4 hours), large steady-state volumes of distribution (2 to 4 l/kg), and high hepatic clearances (10 to 20 ml/kg/min). Alfentanil has a shorter terminal elimination half-life (1 1/2 hours) because of a decreased steady-state volume of distribution (0.5 to 1 l/kg). Physicochemical properties and blood:brain tissue solubility can explain the clinical differences in the rate of onset and dissipation of narcotic effect for these four narcotics. Morphine's low lipid solubility and limited rate of blood:brain barrier penetration results in the slow onset and dissipation of narcotic effect relative to pethidine or fentanyl. Alfentanil's lower blood:brain solubility results in the very rapid onset of narcotic effect when compared to fentanyl. All of the narcotics have a very steep blood concentration:narcotic effect curves. Thus, small changes of narcotic blood concentrations can have profound changes of narcotic effect. Finally, different degrees of perioperative stimuli result in different narcotic blood concentration requirements. Thus, narcotic infusion rates need be varied during surgical procedures to adjust for the varying opiate requirement.