Acetaminophen is an antipyretic and analgesic drug that has a long history of 100 years or more and has been adopted in the WHO Model List of Essential Drugs in the category of non-opioids and non-steroidal anti-inflammatory medicines. In Japan, the analgesic effects of acetaminophen have not been sufficiently recognized, and NSAIDs have been used in the treatment of pain, even though acetaminophen is the first-choice analgesic worldwide.
Since acetaminophen, which is different from NSAIDs, does not inhibit the activity of COX-1 and COX-2, the risk of developing the 3 well-known adverse reactions of NSAIDs, peptic ulcer and gastrointestinal hemorrhage, renal dysfunction, and hemorrhage and platelet dysfunction, is very low. Aspirin is known to induce asthma and Reye's syndrome, however, acetaminophen is scarcely associated with these adverse reactions and can be used for treatment of viral diseases such as chicken pox and influenza. The safety of acetaminophen in pregnant women and elderly patients has been confirmed, and the position of acetaminophen as the first-choice analgesic drug has been established worldwide. In Japan, on the other hand, the effect of acetaminophen has not been sufficiently recognized due to the small doses (single dose, 300-500 mg; daily dose, 900-1500 mg/day) compared to other nations (single dose, 1,000 mg; daily dose, 4000-6000 mg/day). Further, the precautions for use indicated in the package insert of acetaminophen are the same as that indicated for NSAIDs; this may be a possible reason why acetaminophen has been misunderstood to be a kind of anti-inflammatory medication (NSAIDs) in Japan.
From above-mentioned viewpoint, the dosage of acetaminophen and expression of the precautions in packaging insertion should be reconsidered. The dosage of acetaminophen as a nonprescription drug should also be reconsidered because the dosage in OTC is further lower than that of the prescription drug. It is expected that when a more reliable analgesic effect is obtained by the administration of a higher dosage of acetaminophen and a more accurate profile of its safety is recognized, this drug will become the first-choice analgesic in Japan.

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We investigated the influence of pre-administered 2% lidocaine with 1: 80,000 adrenalin on infiltration anesthesia by determining the plasma catecholamine concentrations {plasma adrenalin concentration, plasma noradrenalin concentration} and hemodynamic alterations (changes) {systolic blood pressure, diastolic blood pressure, pulse rate} with bolus administration of 4.0ml of 2% lidocaine with 1: 80,000 adrenalin and those with 0.5ml pre-administration prior to 4.0ml bolus administration (of 2% lidocaine with 1: 80,000 adrenalin). The pre-administration time was established (set) at 3, 5 and 7 minutes prior to bolus administration (4.0ml administration). The study subjects enrolled were 32 healthy male volunteers and categorized into 4 groups: Group I was the bolus administration group, Group II was the 3 minute pre-administration group, Group III was the 5 minute pre-administration group and the Group IV was the 7 minute pre-administration group. Results obtained were as follows:
1. The peak plasma adrenalin concentrations in Groups I, II, and IV were recorded at 5 minutes after administration and at 10 minutes for Group III and then gradually decreased thereafter. The plasma concentration of adrenalin was greatest in Group I followed by Groups II, IV and III, respectively.
2. The plasma concentration of noradrenalin revealed a significant increase in Group I at 10, 15 and 20 minutes following administration.
3. Systolic and diastolic blood pressures both revealed (demonstrated) a significant decrease in the study groups in comparison to the control group.
4. The pulse (heart) rate revealed (demonstrated) a significant increase in the study groups in comparison to the control values.
The pre-administration of 2% lidocaine with 1: 80,000 adrenalin prior to bolus administration suppressed the sudden (sharp) increase in plasma adrenalin concentration and in addition, it is speculated (suggested) to prevent the release of endogenous catecholamines by adrenalin.
In addition, it became clear (evident) that the most effective time to administer the bolus administration was 5 minutes following pre-administration.

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Until recently, Cevimeline hydrochloride hydrate was widely used for dry mouth of patients with Sjögren's syndrome. However, its side effects on the digestive organs may cause patients to reach to loss in quantity of dosage and to discontinue usage. Therefore, we examined the effectiveness and safety of Cevimeline hydrochloride hydrate and Pilocarpine hydrochloride.
Subjects: Nine patients (females, aged 46 to 81 years, average age 63.9) diagnosed as Sjögren's syndrome and receiving the medication of Cevimeline hydrochloride hydrate for 2 months or more, were enrolled in this study.
Evaluation method: Cevimeline hydrochloride hydrate was modified to Pilocarpine hydrochloride, and stimulated saliva flow values, subjective symptoms, drug tolerance, and side effects were compared. In addition, the quantity of drug administered was adjusted by taking into consideration the number of times by the tolerability.
Result: Before the treatment, at the time of Cevimeline hydrochloride hydrate dosage and at the time of Pilocarpine hydrochloride dosage, the stimulated saliva flow values were 4.56 ± 1.81 ml/10 min, 6.07 ± 2.82 ml/10 min and 6.54 ± 2.56 ml/10 min, respectively. As for side effects, Cevimeline hydrochloride hydrate caused various digestive organ conditions, and loss in quantity of dosage was recognized in 3 patients. On the other hand, Pilocarpine hydrochloride showed few side effects, and no patients discontinued the dosage, and no loss in quantity of dosage was observed. Pilocarpine hydrochloride strongly improved subjective and objective symptoms in comparison with Cevimeline hydrochloride hydrate.

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To assess the effect of acetaminophen (Calonal^®) as a pre-emptive analgesic agent for alleviating postoperative pain after removal of impacted lower third molars.
The study protocol was approved by the institutional ethics committee, and the patients gave their informed consent in writing. The subjects were 40 patients with an impacted lower third molar who were randomly divided into 4 groups: (1) control (lactose 1.0g, n = 10), (2) C500 (acetaminophen 500mg, n = 10), (3) C1000 (acetaminophen 1000mg, n = 10), (4) R (flurbiprofen axetil 50mg, n = 10). A vein in all patients was secured and tooth extraction was performed under intravenous sedation. Control, C500 and C1000 were given the medicines orally 30 minutes before the extraction. In R, lactose was given orally and flurbiprofen axetil intravenously 30 minutes before the extraction. The postoperative pain was evaluated by VAS pain score and the pain free period. Statistical analysis was performed using SPSS (Kruskal Wallis and Steel-Dwass tests for the VAS pain scores of each group, Kruskal Wallis and Turkey tests for the pain free period, p < 0.05).
The VAS of C500, C1000 and R were significantly suppressed until 90 minutes after operation. At 120 minutes, the VAS of R and C1000 were significantly decreased compared to C500, but there was no significant difference between R and C1000. The pain free period was extended in the order of C500, C1000 and the R. Although it was significantly extended in C1000 and R compared to the C500 Group, no significant difference was observed between C1000 and R.
Preadministration of acetaminophen is effective in suppressing postoperative pain after tooth removal, and by increasing it up to 1000mg, the effect of pre-emptive analgesia equal to flurbiprofen axetil 50mg can be obtained.

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