James A. Forbes

Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain

Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double‐blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self‐rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti‐inflammatory drugs other than acetaminophen or aspirin.

Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain

We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti‐inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double‐blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose‐response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.

A 12-hour Evaluation of the Analgesic Efficacy of Diflunisal, Propoxyphene, A Propoxyphene-Acetaminophen Combination, and Placebo in Postoperative Oral Surgery Pain

One‐hundred thirty‐two outpatients with pain following oral surgery were randomly assigned, on a double‐blind basis, to a single oral dose of diflunisal 500 or 1000 mg, propoxyphene napsylate 100 mg, a combination of propoxyphene napsylate 100 mg with acetaminophen 650 mg, or placebo. Using a self‐rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Measures of total and peak analgesia were derived from the patients subjective reports. Diflunisal 500 and 1000 mg were significantly superior to placebo and propoxyphene alone for every measure of total and peak analgesia, and the effect of diflunisal persisted for 12 hours. Diflunisal 1000 mg was significantly superior to the propoxyphene‐acetaminophen combination for all measures of analgesia. Although the propoxyphene‐acetaminophen combination was significantly superior to placebo for most measures of analgesia, propoxyphene alone was significantly superior for only two measures. Adverse effects attributed to all drugs were mild and transitory.

A 12-hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen-codeine combination, and placebo in postoperative pain.

The analgesic efficacy of single 500 and 1,000 mg doses of diflunisal, a new nonsteroidal antiinflammatory analgesic, was compared in a double‐blind study with acetaminophen 600 mg, the combination of acetaminophen 600 mg with codeine 60 mg, and placebo in 132 inpatients with postoperative pain. Using a self‐rating record, patients rated their pain and its relief hourly for up to 12 hours after medication. Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia, and a significant analgesic effect persisted for 8 hours. Acetaminophen alone and the acetaminophen‐codeine combination were significantly superior to placebo for most measures of analgesia, and their effects were significant for 4 and 5 hours respectively. Differences among the active medications were not statistically significant for measures of total or peak analgesia.

An Evaluation of the Analgesic Efficacy of Proquazone and Aspirin in Postoperative Dental Pain

The analgesic efficacy of 75, 150, and 300 mg proquazone, a new nonsteroidal antiinflammatory agents, was compared to that of 650 mg aspirin and a placebo in outpatients who had moderate or severe pain following the surgical removal of impacted third molars. Estimates of the relative potency of proquazone to aspirin ranged from 4.9 to 6.2 for total analgesic effect and from 7.7 to 8.4 for peak analgesic effect. Each dosage level of proquazone and aspirin provided significant analgesia compared to placebo and was well tolerated. Adverse effects were transitory and did not appear to be dose related for proquazone.

A method for the 12-hour evaluation of analgesic efficacy in outpatients with postoperative oral surgery pain. Three studies of diflunisal.

We have developed a method for measuring the efficacy of a single dose of an analgesic for 12 hours after administration to outpatients with postoperative oral surgery pain. Using a self‐rating record, patients evaluate their pain and its relief for 12 hours after medication. We have used this method successfully in a series of three studies to compare diflunisal, a new nonsteroidal antiinflammatory analgesic, with placebo and aspirin 650 mg, acetaminophen 600 mg, propoxyphene napsylate 100 mg, or a combination of acetaminophen with either codeine 60 mg or propoxyphene 100 mg. Diflunisal evinced an unusually long duration of analgesic effect. In each study, all doses of diflunisal were significantly superior to placebo through the end of the 12‐hour observation period, while the standards were superior for periods ranging from 2 to 7 hours. In terms of peak analgesia, diflunisal 1,000 mg was comparable to the acetaminophen‐codeine combination and was significantly superior to all the other analgesic standards.

Nalbuphine, acetaminophen, and their combination in postoperative pain

In a double‐blind study with the use of subjective reports of patients as indices of analgesia, we compared the analgesic effect of oral nalbuphine and acetaminophen and determined the contribution of each to the efficacy of their combination. In this parallel 2 × 2 factorial study, 129 inpatients after surgery were randomly assigned to treatment with a single oral dose of nalbuphine hydrochloride (30 mg), acetaminophen (650 mg), the combination of nalbuphine (30 mg) and acetaminophen (650 mg), or placebo. In the factorial analysis, both the nalbuphine and acetaminophen effects were significant for virtually every measure of total and peak analgesia, whereas the interaction contrast was not significant for any measure of analgesic effect. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the results of studies of combinations of codeine and other opioids with aspirin or acetaminophen. There were few adverse effects other than sedation, which occurred twice as frequently in patients treated with nalbuphine as in those receiving acetaminophen or placebo. Our data suggest that this combination should prove at least as effective as any currently marketed narcotic‐containing combination. Since nalbuphine has less dependence liability than narcotics and exhibits a ceiling on respiratory depression, its combination with acetaminophen should also be safer than comparable narcotic combinations.

Evaluation of an ibuprofen controlled-release tablet and placebo in postoperative oral surgery pain.

Seventy‐four outpatients with postoperative pain after oral surgery were randomly assigned, on a double‐blind basis, to receive a single oral dose of a controlled‐release tablet (CRT) containing 600 mg ibuprofen, two 600‐mg ibuprofen CRTs, or placebo. Using a self‐rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of total and peak analgesia were derived from these subjective reports. The ibuprofen CRTs (600 and 1200 mg) had manifested an analgesic effect by hour 1 and their efficacy persisted for 12 hours. Comparable effect for the two ibuprofen CRT dosages could suggest a plateau in analgesia at the 600‐mg level or a lack of upside assay sensitivity. Duration of effect was longer for the CRTs than we have previously observed with conventional ibuprofen tablets. Adverse effects were transitory and consistent with the known pharmacologic profile of the medication evaluated.

A Double‐Blind Evaluation of the Nocturnal Antisecretory Effects of Anisotropine Methylbromide in Man. Dose Response and Duration of Action Studies

The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without significantly influencing heart rate, blood pressure, visual acuity, or visual accommodation. The duration of action of large doses was then evaluated in fasted and nonfasted subjects. A single dose reduced acid secretion for up to 8 hours, eliminating the nocturnal elevation of acid secretion characteristic of the normal circadian pattern. Near visual acuity and accommodation decreased, an effect more pronounced in fasted subjects, but the magnitude of visual impairment was small. These findings provide the basis for a controlled trial of high-dose nighttime therapy in peptic ulcer disease.