Search

Cyclophosphamide (177 mg/kg, IV; n = 8) produced a biphasic emetic response in the ferret with a mean ± SE of 23.3 ± 4.0 emetic episodes during a 4-h observation period. The emetic profile of cyclophosphamide showed a first phase with 18.6 ± 3.9 episodes and a second phase with 4.7 ± 1.2 episodes. Ondansetron (0.07 and 0.13 mg/kg, IV) and droperidol (0.25 and 0.79 mg/kg, IV) significantly reduced the number of emetic episodes in the first phase. Metoclopramide (2.24, 4.08, and 7.07 mg/kg, IV) also significantly reduced the number of emetic episodes in the first phase, and the dose of 7.07 mg/kg completely prevented emetic episodes in the second phase. In addition, ondansetron-treated ferrets (0.04, 0.07, and 0.13 mg/kg, IV) had a significant increase in the number of emetic episodes in the second phase.

The rabbit tooth-pulp assay is well established as a method for measuring the efficacy and potency of parenteral analgesic drugs. We describe a method for administration of local anesthetic drugs into the maxillary arch and subsequent measurements of antinociceptive action. It was possible to use two different methods of ED50 estimation and to provide measures of the potency, efficacy, and duration of local anesthetic drugs. These measurements corresponded with in vitro estimates of potency and duration and with intrinsic observations of the clinical actions.

Structural changes to the fentanyl molecule based on heterocyclic modifications at the sector distal to the piperidine nitrogen results in morphine reversal activity. A series of such compounds known as 4-(heteroanilido) piperidines were tested for reversal of morphine antinociception and depressed respiration rate per minute (RPM) using a rabbit tooth pulp model. Nine compounds were tested and all reversed morphine depressed RPM with doses ranging from 0.007 mg/kg to 1.55 mg/kg. Four of the nine compounds also significantly reversed antinociception at doses ranging from 0.005 mg/kg to 0.6 mg/kg. All but one compound elicited significant antinociception in non-morphine rabbits. Maximum possible effect (MPE) ranged from 21% to 57% and cumulative doses to achieve antinociception ranged from 0.16 mg/kg to 7.7 mg/kg. These compounds increased RPM in non-morphine rabbits with a range from 9% to 49% over control values. A furan ring at the distal site was found to be important in selective reversal of RPM. When a methylated 2-pyridine was combined with a 2-furan, reversal of both morphine antinociception and depressed RPM was achieved. One compound in this series compared favorably to the mixed agonist-antagonist nalbuphine and a second compared favorably to the pure antagonist naloxone.

Antinociception of imipramine (I) and its effect in combination with fentanyl (F) was evaluated in rabbits using electrically-induced lick chew responses via tooth pulp stimulation as the model of nociception. Acute i.v. injections of I elicited a graded dose response comparable to i.v. morphine (M) with I ED 50 = 4.35 mg/kg (2.31-8.14, 95% CL) and M ED 50 = 1.81 mg/kg (1.11-3.90), with no differences in the slopes between the two curves. The lethal dose of I was 10 mg/kg. An i.v. dose of I twice the ED 50 elicited an antinociceptive effect of more than 50% maximum possible effect (MPE) for 90 minutes with peak effect of 82% MPE occurring at 15 minutes. These effects of I were not reversed by a morphine-reversal dose of naloxone (0.1 mg/kg i.v.) but were reversed with a ten fold dose of naloxone. F ED 50 values (mcg/kg) were lowered from 11.35 to 2.70, 0.74 and 0.33 with increasing pretreatment doses of I (1.0, 2.1 and 3.2 mg/kg). These magnitudes of potency increases of F were 4.2, 15.3 and 34.4 fold respectively. A single i.v. ED 50 dose of I extended the time to 50% MPE of an ED 90 dose of F from 26 minutes to 77 minutes; of a 2 X ED 50 dose of F from 17 minutes to 28 minutes. Data points for three different combinations of I and F fell significantly within the synergistic field of an ED 50 isobologram and a polynomial equation described the curve best fitting the data points. F alone (i.v. ED 50 dose) increased the PaCO2 values to 74% above controls and three different combinations with I showed no increases in PaCO2 values above controls. I alone did not significantly cause any change in PaCO2 values from controls.

Aspirin use in the United States remains high because of its diverse and beneficial activities. In adults at risk for cardiovascular thrombotic events, low-dose aspirin is an excellent preventive agent; however, its antiplatelet properties have contributed to a perceived increased risk for bleeding after dental extractions. This article discusses recent evidence regarding the thrombotic risks associated with discontinuing aspirin use in patients who take aspirin daily and presents a new recommendation for continuing low-dose aspirin during invasive dental procedures.