Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study.

PURPOSE: Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg, and placebo were investigated to establish the multidimensional pharmacodynamic profiles of each drug on acute pain with calculated effect size estimates. METHODS: A randomized, double-blind, single-dose, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 350 patients (mean age 25 year, range 18 to 30 years) of homogenous ethnicity after third molar surgery. Primary outcome was sum pain intensity over 6 h. Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference, maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat values, adverse effects, overall drug assessment as patient-reported outcome measure (PROM), and the effect size estimates NNT and NNTp. RESULTS: Ibuprofen doses above 400 mg do not significantly increase analgesic effect. Paracetamol has a very flat analgesic dose-response profile. Paracetamol 1000/codeine 60 mg gives similar analgesia as ibuprofen from 400 mg, but has a shorter time to analgesic onset. Active drugs show no significant difference in maximal analgesic effect. Other secondary outcomes support these findings. The frequencies of adverse effects were low, mild to moderate in all active groups. NNT and NTTp values did not coincide well with PROMs. CONCLUSION: Ibuprofen doses above 400 mg for acute pain offer limited analgesic gain. Paracetamol 1000 mg/codeine 60 mg is comparable to ibuprofen doses from 400 mg. Calculated effect size estimates and PROM in our study seem not to relate well as clinical analgesic efficacy estimators. TRIAL REGISTRATION: NCT00699114.

[Adverse drug effects in the oral region]. / Legemiddelbivirkninger i munnhulen.

Syphilis was previously termed "the great imitator" because so many of the signs and symptoms are indistinguishable from those of other diseases. This role has been taken over by drugs, and this also applies to adverse drug reactions in the oral region. Accordingly, a careful drug history, including identification of any prescription, over-the-counter, or herbal medicines used, may give an important clue to the differential diagnosis of oral diseases when the aetiology is not apparent. Virtually all drugs have the potential to cause oral adverse reactions, but some have a greater ability to do so than others. Among the numerous adverse oral manifestations are xerostomia, taste disturbances and ulceration. The reactions are often non-specific, but they may mimic specific disease states such as erythema multiforme, lichen planus and pemphigus. Drug-induced gingival hyperplasia is an example of a quite characteristic and easily recognisable oral side effect. This article briefly describes some of the presentations and mechanisms of oral manifestations of drug therapy and the drugs that most commonly are responsible. Just like approved pharmaceuticals, herbal medicines are also associated with adverse oral manifestations. Finally we comment on some of the more recent reports on osteonecrosis of the jaws associated with the use of bisphosphonates.

Good evidence for effectiveness of analgesics most commonly prescribed by UK dentists. What is the relative efficacy of single-dose oral analgesics after third molar extraction?

DATA SOURCES: Dental trials were sought among systematic reviews of randomised, double-blind studies of analgesics in acute pain, which were identified from the Cochrane Library, Biological Abstracts, MEDLINE, PubMed and the Oxford Pain Relief database. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by two reviewers. Dichotomous information from active and placebo treatments was used, first to calculate the statistical significance using relative risk, and then to evaluate the clinical relevance using number-needed-to-treat (NNT). RESULTS: Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase (COX)-2 inhibitors had the lowest (best) NNT for the outcome of pain at least halved over 4-6 h compared with placebo. With the best performing analgesics, 50-70 patients out of 100 had good pain relief compared with about 10 out of 100 with placebo. Only paracetamol (600/650 mg) plus codeine (60 mg) was associated with any significant increase in any patient experiencing an adverse event. CONCLUSIONS: NSAID and COX-2 inhibitors have the lowest (best) NNT. These may also have fewer adverse effects after third molar surgery, but conclusive evidence is lacking. At least 80% of analgesic prescribing by UK dentists is in line with the best available evidence on efficacy and safety.

Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain.

We examined the analgesic effect of racemic ketamine and its 2 enantiomers in 16 female patients (age: 20-29 years) suffering acute pain after oral surgery and in 7 female patients (age: 42-79 years) suffering chronic neuropathic orofacial pain. All 3 forms of ketamine consistently relieved postoperative pain, (S)-ketamine being 4 times more potent than (R)-ketamine. The analgesic effect was maximal 5 min after i.m. injection and lasted for about 30 min. The 7 patients with neuropathic pain received ketamine at one or several occasions. Four patients (age: 54-79 years) who had suffered pain for more than 5 years did not experience an analgesic effect, whereas 3 patients (age: 42-53 years) who had suffered pain for less than 3 years reported pain relief lasting from 24 h to 3 days. The individual type of response did not depend on the form of ketamine used. The mental side effects were qualitatively similar for the 3 forms of ketamine. Relative to the analgesic effect (S)-ketamine caused more disturbing side effects than did (R)-ketamine. The mean serum concentration of each form of ketamine at the time of maximal effect was close to the approximate Kd value for PCP site occupancy by that particular form. This is in concert with the hypothesis that the effect of ketamine on acute nociceptive pain is due to N-methyl-D-aspartate (NMDA) receptor inhibition and adds to the evidence that NMDA receptors are important for the perception of acute, nociceptive pain in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of ketamine and pethidine in experimental and postoperative pain.

The analgesic efficiency of ketamine and pethidine was compared in experimental ischemic pain and postoperative pain after oral surgery. Naloxone 1.6 mg or placebo was given 5 min before the analgesic drug. The subjects recorded their pain on a visual analogue scale. Both ketamine 0.3 mg/kg and pethidine 0.7 mg/kg were effective as analgesics against the two types of pain studied. Naloxone prevented the analgesic effect of pethidine, but had no effect on ketamine analgesia. The results are in accordance with the hypothesis that the analgesic effect of ketamine is mediated by a non-opioid mechanism, possibly involving PCP-receptor-mediated blockade of the NMDA-receptor-operated ion channel.