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Optimal Timing of Intravenous Acetaminophen Administration for Postoperative Analgesia
Maho Shinoda DDS,
 Akiko Nishimura DDS, PhD,
 Erika Sugiyama PhD,
 Hitoshi Sato PhD, and
 Takehiko Iijima DDS, PhD
Article Category: Research Article
Volume/Issue: Volume 69: Issue 2
Online Publication Date: Jul 18, 2022
DOI: 10.2344/anpr-69-02-05
Page Range: 3 – 10

Acetaminophen (APAP) is an analgesic that is widely used to relieve postoperative pain. APAP is thought to act as a substrate for the peroxidase activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and to exert its anti-inflammatory and analgesic effects by decreasing prostaglandin H2 through competition with prostaglandin G2. 1 Furthermore, the similarity of its in vivo action to that of selective COX-2 inhibitors has been confirmed. 2 , 3 Although APAP was originally thought to act peripherally, accumulating data now support

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An Evaluation of Ibuprofen Versus Ibuprofen/Acetaminophen for Postoperative Endodontic Pain in Patients With Symptomatic Irreversible Pulpitis and Symptomatic Apical Periodontitis
Alex Stamos DDS, MS,
 Melissa Drum DDS, MS,
 Al Reader DDS, MS,
 John Nusstein DDS, MS,
 Sara Fowler DMD, MS, and
 Mike Beck DDS, MA
Article Category: Research Article
Volume/Issue: Volume 66: Issue 4
Online Publication Date: Jan 01, 2019
DOI: 10.2344/anpr-66-03-06
Page Range: 192 – 201

Systematic and Cochrane reviews have found superior postoperative pain control with combinations of ibuprofen/acetaminophen versus use of either medication alone. 1 – 4 However, these reviews were largely based on third molar extraction models in young adults who have no pain or pre-existing infections. As stated by Moore and Hersh, 5 the efficacies of ibuprofen combined with other nonsteroidal anti-inflammatory drugs differ depending on the model being studied. They further stated that additional research evaluating postoperative pain

Figure 4 ; Percentage of patients taking ibuprofen, ibuprofen/acetaminophen, and opioid. Opioid percentages are presented on top of the ibuprofen and ibuprofen/acetaminophen percentages.
Alex Stamos,
 Melissa Drum,
 Al Reader,
 John Nusstein,
 Sara Fowler, and
 Mike Beck
<bold>Figure 4</bold>
Figure 4

Percentage of patients taking ibuprofen, ibuprofen/acetaminophen, and opioid. Opioid percentages are presented on top of the ibuprofen and ibuprofen/acetaminophen percentages.

Figure 2 ; Percentages and discomfort ratings of postoperative pain for the ibuprofen and ibuprofen/acetaminophen groups by day. patients requiring opioids were excluded on days 2–4.
Alex Stamos,
 Melissa Drum,
 Al Reader,
 John Nusstein,
 Sara Fowler, and
 Mike Beck
<bold>Figure 2</bold>
Figure 2

Percentages and discomfort ratings of postoperative pain for the ibuprofen and ibuprofen/acetaminophen groups by day. patients requiring opioids were excluded on days 2–4.

Figure 3 ; Percentages and discomfort ratings of postoperative percussion pain for the ibuprofen and ibuprofen/acetaminophen groups by day. Patients requiring opioids were excluded on days 2–4.
Alex Stamos,
 Melissa Drum,
 Al Reader,
 John Nusstein,
 Sara Fowler, and
 Mike Beck
<bold>Figure 3</bold>
Figure 3

Percentages and discomfort ratings of postoperative percussion pain for the ibuprofen and ibuprofen/acetaminophen groups by day. Patients requiring opioids were excluded on days 2–4.

Figure 3.; Relationship between plasma acetaminophen (APAP) concentration and pain equivalent current (PEC) value (Figure 2B). The plasma APAP concentration reached its highest level immediately after administration, but the analgesic effect peaked at 180 minutes after administration. Note that the target effect was substantially delayed after the peak of the plasma concentration.
Maho Shinoda,
 Akiko Nishimura,
 Erika Sugiyama,
 Hitoshi Sato, and
 Takehiko Iijima
Figure 3.
Figure 3.

Relationship between plasma acetaminophen (APAP) concentration and pain equivalent current (PEC) value (Figure 2B).

The plasma APAP concentration reached its highest level immediately after administration, but the analgesic effect peaked at 180 minutes after administration. Note that the target effect was substantially delayed after the peak of the plasma concentration.

Figure 4.; The pharmacokinetic-pharmacodynamic (PK-PD) model developed using the acetaminophen (APAP) plasma concentration and pain equivalent current (PEC) data. The PK model (A) was developed using a 2-compartment model, and PD model (B) was developed using a linear model and an effect compartment model. The symbols represent the mean and standard error (SE) that were obtained in 15 subjects. Open circles and the dashed line represent the duration of the analgesic effect of APAP estimated by PK-PD model.
Maho Shinoda,
 Akiko Nishimura,
 Erika Sugiyama,
 Hitoshi Sato, and
 Takehiko Iijima
Figure 4.
Figure 4.

The pharmacokinetic-pharmacodynamic (PK-PD) model developed using the acetaminophen (APAP) plasma concentration and pain equivalent current (PEC) data.

The PK model (A) was developed using a 2-compartment model, and PD model (B) was developed using a linear model and an effect compartment model. The symbols represent the mean and standard error (SE) that were obtained in 15 subjects. Open circles and the dashed line represent the duration of the analgesic effect of APAP estimated by PK-PD model.

Figure 2.; Rate of change in current perception threshold (CPT) (A) and pain equivalent current (PEC) (B) in the acetaminophen (APAP) and control groups. No significant difference in the rate of CPT change was seen between the APAP and control groups (Figure 1A). On the other hand, the rate of PEC change was significantly higher in the APAP group than in the control group, and the PEC in the APAP group differed significantly at time points between 90 and 300 minutes compared with the PRE value (Figure 1B). * P < .05 (vs PRE value).
Maho Shinoda,
 Akiko Nishimura,
 Erika Sugiyama,
 Hitoshi Sato, and
 Takehiko Iijima
Figure 2.
Figure 2.

Rate of change in current perception threshold (CPT) (A) and pain equivalent current (PEC) (B) in the acetaminophen (APAP) and control groups.

No significant difference in the rate of CPT change was seen between the APAP and control groups (Figure 1A). On the other hand, the rate of PEC change was significantly higher in the APAP group than in the control group, and the PEC in the APAP group differed significantly at time points between 90 and 300 minutes compared with the PRE value (Figure 1B).

* P < .05 (vs PRE value).

Assessing the Effectiveness of Combined Analgesics for Bilateral Ramus Osteotomies
Shigeru Maeda DDS, PhD,
 Hitoshi Higuchi DDS, PhD,
 Maki Fujimoto DDS,
 Saki Miyake DDS,
 Yuka Honda-Wakasugi DDS, PhD, and
 Takuya Miyawaki DDS, PhD
Article Category: Research Article
Volume/Issue: Volume 67: Issue 3
Online Publication Date: Sep 29, 2020
DOI: 10.2344/anpr-67-01-05
Page Range: 140 – 145

, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used and have been shown to be effective. 4 , 5 For major surgeries, in addition to NSAIDs and/or acetaminophen, intravenous patient-controlled analgesia (IV-PCA) or epidural PCA of opioids are common and effective options for pain management. 6 Although an uncomplicated ramus osteotomy could be considered a minor surgical procedure if performed efficiently, it occasionally takes a longer time with increased risks and difficulties, such as issues ensuring hemostasis or severe edema of the mandible

A Comparative Study of Oral Analgesics for Postoperative Pain After Minor Oral Surgery
Atsushi Hanzawa DDS, PhD,
 Toshiyuki Handa DDS, PhD,
 Yoshihiko Kohkita DDS, PhD,
 Tatsuya Ichinohe DDS, PhD, and
 Ken-Ichi Fukuda DDS, PhD
Article Category: Research Article
Volume/Issue: Volume 65: Issue 1
Online Publication Date: Jan 01, 2018
DOI: 10.2344/anpr-65-01-02
Page Range: 24 – 29

are desirable. Preparations recommended for use in postoperative analgesia include opioid analgesics, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase (COX)-2 inhibitors, and acetaminophen. 7 In the field of oral surgery, nonselective NSAIDs have been frequently used for postoperative pain relief. 8 However, there is concern about gastrointestinal dysfunction and suppression of platelet function with the administration of nonselective NSAIDs because of inhibition of prostaglandin and thromboxane synthesis by COX-1. 9