title: Alfentanil's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs.
abstract: Relationships between plasma concentrations of alfentanil and its analgesic, respiratory, and cardiovascular effects were determined in dogs. To avoid drug interaction, trained, unanesthetized, spontaneously breathing dogs were used. After a control period in the awake state, alfentanil was injected in increasing amounts (10, 20, 80, 160, and 320 micrograms/kg) at 5-min intervals to a total dose of 590 micrograms/kg administered over 20 min. The effects were observed on pain responses (heart rate and blood pressure changes and somatic reactions to tail clamping), respiration (respiratory rate, oxygen consumption [VO2], blood gas tensions) and circulation (heart rate and blood pressure). The plasma concentration-effect curves, derived by relating the changes in multiple variables from the awake state to the corresponding plasma concentrations (range 8-5079 ng/ml), plateaued at and around 200 ng/ml during the injection period but were displaced in parallel to two-fold higher concentrations during recovery, which resembles acute tolerance. At maximally effective analgesic concentrations, which precipitated profound cardiorespiratory slowing with conspicuous hypoxemia, the VO2 of 4.4 +/- 0.3 ml X kg-1 X min-1 corresponded with the calculated metabolic rate but increased to 6.3 +/- 1.6 ml X kg-1 during recovery. The analgesic action of alfentanil, which cannot be separated from its depressant cardiorespiratory effects and maximally effective analgesic concentrations (between 200 and 400 ng/ml), apparently does not jeopardize the adequacy of tissue oxygenation in dogs.
authors.forename: J O
authors.initials: JO
authors.lastname: Arndt
authors.forename: B
authors.initials: B
authors.lastname: Bednarski
authors.forename: C
authors.initials: C
authors.lastname: Parasher
mesh_terms: D015760:Alfentanil; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001364:Awareness / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002849:Chromatography, Gas; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010146:Pain / Q000517:prevention & control; D012119:Respiration / Q000187:drug effects; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil; D005283:Fentanyl