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D D Denson

Publications and source records attributed to D D Denson.

80 records · Page 5Linked to original sources
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Ion-trapping of meperidine: influence of antacid treatments on serum and gastric fluid concentrations.

The ascorbic acid pretreated beagle dog was used to demonstrate the phenomenon of ion-trapping and the influence of three different antacid treatments on the serum and gastric fluid concentration of meperidine: pretreatment with magnesium-aluminum hydroxide (MA), pretreatment with cimetidine (C), and periodic total aspiration of gastric fluid (ASP). A significant correlation between pH and the meperidine concentration in gastric fluid was found; the lower the pH the higher is the secretion of meperidine into gastric fluid. The gastric fluid meperidine concentrations were 8-30 times as high as the respective serum concentrations. No significant differences between the meperidine concentration in the gastric fluid were found among the three treatments, MA, C, or ASP, versus control. Meperidine serum concentrations differed significantly versus control on two times for MA and on one time for ASP. The elimination half-life [h] and the mean residence time [h] differed significantly in the MA treatment (1.15 +/- 0.02 h and 1.23 +/- 0.24 h) versus control (1.90 +/- 0.19 h and 2.00 +/- 0.15 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Hydroxide↗
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The effect of rate of infusion on continuous epidural analgesia for labor and delivery.

The authors previously reported that if a loading dose of 50 mg bupivacaine was followed by infusion of 0.0625% bupivacaine (12.5 mg/hr), supplemental doses to achieve satisfactory analgesia for labor and delivery were required in 50% of patients. The current study was done to determine whether increasing the dose from 12.5 to 25 mg/h would eliminate the need for supplemental injections. Twenty-three healthy parturients were randomly assigned to one of two groups--Group I: 0.125% bupivacaine at 20 ml/hr (25 mg/hr); or Group II: 0.25% bupivacaine at 10 ml/hr (25 mg/hr). Taking both groups together, the 50-mg bupivacaine loading dose followed by 25 mg/hr provided adequate analgesia for labor and delivery in 74% of the patients. Two parturients in Group I and three in Group II required supplemental boluses of 4 ml of 0.5% bupivacaine for delivery. Pharmacokinetic data were similar in both groups. Using a dose of 25 mg/hr resulted in 74% of the patients obtaining adequate analgesia for labor and delivery. This improvement over the 50% success rate in the previous study, was achieved without any evidence of toxicity.

Adult↗
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Threshold serum concentrations of bupivacaine associated with early CNS toxicity and pharmacokinetics of bupivacaine in young versus old rhesus monkeys.

Effects of aging on the onset of early signs of central nervous system (CNS) toxicity, associated total and free arterial threshold serum concentration, and the disposition of bupivacaine were studied in eight younger (11-15 years) and eight older (16-28 years) rhesus monkeys. Bupivacaine was infused at a rate of 0.15 mg/kg minute until unceasing movements of the eye, oscillating from side to side and up and down (nonpositional nystagmus). This was regarded as an objective sign of early CNS toxicity. Most animals showed drowsiness and sedation by the end of the infusion. CNS toxicity occurred significantly faster (p less than 0.025) in the younger (13.7 +/- 2.5 minutes) than in the older (17.1 +/- 2.6 minutes) animal group. A significant correlation was found between the onset time of CNS toxicity and age. The coefficient of determination (R2) for this correlation was 0.48. Also, the dose associated with the onset of CNS toxicity was significantly smaller in the younger (2.06 +/- 0.38 mg/kg) than in the older (2.60 +/- 0.39 mg/kg) animals. However, the total and free arterial threshold serum concentration of bupivacaine was similar in both groups. Age did not influence the disposition of bupivacaine.

Aging↗
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Absorption of bupivacaine after topical application to the oropharynx.

Bupivacaine in dosages of 20, 40, 60, or 80 mg was applied by spray to the oropharynx of 24 volunteers. Blood levels of bupivacaine were detectable at 10 minutes, peaked at 60-90 minutes, and were still measurable at 150 minutes after administration. The maximum bupivacaine plasma level recorded in any volunteer was 0.96 -g/mL (after 80 mg). Increase in pulse rate and decrease in systolic blood pressure were significantly correlated with increasing bupivacaine dosage. No clinical signs or symptoms of drug toxicity were observed in any subject.

Absorption↗
PubMedDate not supplied

Influence of cimetidine on bupivacaine disposition in rat and monkey.

Recent reports have appeared describing a cimetidine-induced alteration in either the input or disposition function for many drugs. The total clearance component of the disposition function is the primary perturbation. In the present investigation, the influence of cimetidine on bupivacaine disposition was studied, using in vitro and in vivo models. Since the extraction ratio for bupivacaine is low, total clearance follows the capacity-limited theory. Hence, the influence of cimetidine on the intrinsic clearance of bupivacaine was assessed using microsome and hepatocyte models. Results for both systems are in excellent agreement and indicate a noncompetitive inhibition. Additionally, the influence of cimetidine on the protein-binding profile of bupivacaine was determined. In the presence of cimetidine, the these findings was assessed in vivo in rhesus monkeys. co-administration of cimetidine resulted in an increase in the volume of distribution at steady state and no change in the total clearance of bupivacaine.

Animals↗
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Comparison of the efficacy of epidural morphine given by intermittent injection or continuous infusion for the management of postoperative pain.

BACKGROUND AND OBJECTIVES: To compare the effectiveness and side effects of epidural morphine sulfate (MSO4), delivered by continual infusion or intermittent bolus. METHODS: Thirty patients undergoing upper abdominal surgery were randomized into two equal groups to receive MSO4 through a thoracic epidural catheter by one of two methods. Group 1 patients received an initial bolus of morphine (0.07 mg/kg) at the end of surgery, followed by injections of 2-5 mg morphine into the epidural catheter on demand. Patients in group 2 received an initial bolus of morphine (0.03 mg/kg) during surgical peritoneal closure and were immediately started on an infusion of 0.01% morphine at 5 mL/hour (0.5 mg/hour). The infusion dose was titrated from 0.2 to 1.0 mg/hour, dependent on side effects. Outcome measurements included pulmonary function studies, arterial blood gases, morphine plasma levels, pain relief scores, global evaluations, and side effects. RESULTS: No difference existed between groups in forced vital capacity, forced expiratory volume in 1 second, or in arterial blood gas measurements. Side effects were similar in both groups. Respiratory depression was not seen in either group. Group 2 reported significantly better analgesia than group 1 on postoperative days 1 and 2 (P < .01). Peak plasma morphine levels for group 1 were significantly higher than the steady state plasma morphine levels for group 2 (P < .05). CONCLUSIONS: Continuous epidural infusion provides better analgesia without increased side effects for postoperative pain when compared with an intermittent (or demand) bolus technique.

Abdomen↗