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Biomedical subjects

W T Beaver

Publications and source records attributed to W T Beaver.

At least 19 recordsLinked to original sources

Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain.

Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. In both studies, the combination was significantly superior to placebo for sum of the pain intensity differences (SPID), total pain relief (TOTPAR), peak pain intensity difference (PID) and pain relief, global evaluation, and time to remedication. The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents.

Adult↗

Caffeine as an analgesic adjuvant in tension headache.

Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches. In four studies, comprising 1900 patients, the caffeine-containing analgesic consisted of a combination of 500 mg acetaminophen, 500 mg aspirin, and 130 mg caffeine (APAP/ASA/CAF). In two studies, comprising 911 patients, the caffeine-containing analgesic consisted of a combination of 1000 mg acetaminophen and 130 mg caffeine (APAP/CAF). Patients self-medicated for moderate or severe headache pain, and with a self-rating record they rated their pain and its relief hourly for 4 hours. In all six studies, the caffeine-containing analgesics were significantly superior both to placebo and to 1000 mg acetaminophen, and acetaminophen was significantly superior to placebo. The significant analgesic adjuvant effect of caffeine was independent of patients' usual caffeine use or their caffeine consumption in the 4 hours before medication. For each treatment, the pooled analgesic responses for the four studies of APAP/ASA/CAF were virtually superimposable on the responses in the two APAP/CAF studies. The combinations produced more stomach discomfort, nervousness, and dizziness than acetaminophen or placebo.

Acetaminophen↗

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.

Aspirin↗

The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study.

Twenty severely retarded institutionalized epileptic adults with phenytoin-induced gingival hyperplasia were divided into two groups and received a daily 3 mg capsule of either folic acid or lactose for 16 weeks in a randomized, double-blind, parallel study. Serum folate and phenytoin levels were recorded at baseline and on completion of the study. Twelve areas of the gingiva on each patient were graded at 4-week intervals for 16 weeks with respect to the three indexes: hyperplasia, gingival health, and plaque index. There were no significant differences between treatment groups for any of the three indexes over time. The poststudy serum folate levels were three times baseline levels for the active drug group (p less than 0.001) but unchanged in the placebo group. Phenytoin blood levels that began within the therapeutic window (10 to 20 micrograms/ml) tended to remain within the therapeutic window for both groups, with no reported seizure activity. A single daily oral 3 mg capsule of folic acid did not show efficacy as the sole therapeutic agent in the reduction of phenytoin-induced gingival hyperplasia.

Adult↗

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.

Adolescent↗

On the mechanism of drug-induced gingival hyperplasia.

Proposed mechanisms of the side effect of drug-induced gingival hyperplasia are reviewed. Hypotheses with regard to inflammation from bacterial plaque, increased sulfated glycosaminoglycans, immunoglobulins, gingival fibroblast phenotype population differences, epithelial growth factor, pharmacokinetics and tissuebinding, collagenase activation, disruption of fibroblast cellular sodium/calcium flux, folic acid and a combination hypothesis are evaluated.

Dental Plaque↗

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.

Administration, Oral↗

Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain.

Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated.

Administration, Oral↗

Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin.

Acetaminophen↗

Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.

Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.

Acetaminophen↗

Evaluation of aspirin, caffeine, and their combination in postoperative oral surgery pain.

Three hundred fifty outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments except caffeine were significantly superior to placebo. Pairwise comparisons indicated the aspirin-caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were serious.

Administration, Oral↗

An evaluation of flurbiprofen, aspirin, and placebo in postoperative oral surgery pain.

One hundred sixty-four outpatients with postoperative pain after the removal of impacted third molars were randomly assigned on a double-blind basis, to receive oral doses of flurbiprofen 25, 50, or 100 mg; aspirin 600 mg; or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 8 hours after medicating. Estimates of sum of pain differences (SPID), peak pain intensity difference (PID), total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active medications were significantly superior to placebo. Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg. Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID. There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages. Flurbiprofen 50 and 100 mg did not differ significantly, suggesting a plateau in flurbiprofen's analgesia. The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours. The frequency of adverse effects was similar for the active medications.

Adolescent↗

Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.

Eighty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single, oral dose of flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.

Acetaminophen↗

Impact of non-narcotic oral analgesics on pain management.

Of the four categories of oral analgesics, three have been available since the 19th century. Although adequate doses of the more potent oral opioids such as morphine and methadone are effective even in severe pain, the commonly used "weak" narcotics such as codeine and propoxyphene are no more effective than usual doses of aspirin or acetaminophen. Furthermore, the opioids produce gastrointestinal and central nervous system adverse effects, and, during long-term administration, tolerance may develop and there is a risk of drug dependence. Aspirin and acetaminophen are the traditional agents of choice for oral analgesic therapy; until 10 years ago, there were no single-entity, oral analgesics--with the exception of large doses of oral narcotics--that were more effective than usual doses of aspirin or acetaminophen. However, there is a ceiling on the analgesic effect attainable with safe doses of these drugs, which may in part be overcome through the use of the third category of oral analgesics, combinations of aspirin or acetaminophen with oral opioids. The fourth category of oral analgesics constitutes the most important recent development in pain management with analgesic drugs: the newer peripherally acting, nonsteroidal anti-inflammatory analgesics, some of which are clearly more efficacious than aspirin or acetaminophen and compare favorably not only with full doses of narcotic combination products but even, in some cases, with strong injectable opioids. On repeated dosing, some nonsteroidal anti-inflammatory drugs are better tolerated than aspirin and some have a much longer duration of analgesic effect than aspirin or acetaminophen. Further study is needed to compare nonsteroidal anti-inflammatory drugs among themselves and to determine their value in chronic pain and in combination therapy.

Acetaminophen↗

Combination analgesics.

Six rationales for using combination analgesics are identified, but most combinations are formulated with two rationales in mind: enhancement of analgesia and reduction of adverse effects by combining two analgesics with different mechanisms of action. Acetaminophen and aspirin are the mainstays of oral analgesic combinations. There is substantial evidence that combining an optimal dose of acetaminophen or aspirin with an oral opioid such as codeine, hydrocodone, or oxycodone produces an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equi-analgesic dose of a single constituent. The physician need not be confined to existing fixed-ratio combinations; he or she may extemporize to the patient's advantage by co-administering acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs with available oral opioids and, in select situations, co-administering oral or injectable analgesics with psychoactive drugs.

Acetaminophen↗

Caffeine revisited.

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Adjuvants, Pharmaceutic↗