Acute tolerance to fentanyl during anesthesia in dogs.
The effect of fentanyl on increases in heart rate and mean arterial pressure elicited by electric stimulation of a branch of the radial nerve was studied in anesthetized, paralyzed, and artificially ventilated dogs. In one group, a bolus of 100 micrograms/kg of fentanyl depressed the evoked changes in heart rate and arterial pressure by 82 and 75%, respectively, by 5 min, and recovery occurred within 90 min. A second group was given increasing bolus doses of fentanyl from 1.5 to 100 micrograms/kg every 20 min for 200 min. The doses and intervals were chosen to give a logarithmic increase in plasma concentration of fentanyl to include a final bolus dose of 100 micrograms/kg and were predicted by a two-compartment pharmacokinetic model derived from data of the first group. In the second group, the bolus dose of 100 micrograms/kg after 5 min had no significant effect on evoked cardiovascular responses. Over the following 2 h, the evoked changes in heart rate and arterial pressure increased above those preceding the 100 micrograms/kg dose. An additional bolus dose of 100 micrograms/kg given 2 h after the first did not depress the evoked reflexes below the control values. It was concluded that tolerance to the effects of fentanyl can occur within 3 h and that for evoked responses to arterial pressure, rebound withdrawal effects can be seen within an additional 90 min.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005283:Fentanyl / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007700:Kinetics; D008954:Models, Biological; D013997:Time Factors
D005283:Fentanyl