Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania.

BACKGROUND: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years). TYPES OF STUDIES REVIEWED: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. RESULTS: The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.

Do buffered local anesthetics provide more successful anesthesia than nonbuffered solutions in patients with pulpally involved teeth requiring dental therapy?: A systematic review.

BACKGROUND: The authors conducted a systematic review that addresses the following population, intervention, comparison, outcome question: "In adults requiring dental therapy with pulpally involved teeth, what is the comparative efficacy of buffered local anesthetics (LAs) compared with that of nonbuffered LAs in achieving anesthetic success?" TYPES OF STUDIES REVIEWED: The authors searched MEDLINE, Scopus, Cochrane Library, ClinicalTrials.gov, World Health Organization International Trials Registry Platform, OpenGrey, Google Scholar Beta, and 2 textbooks to identify double-blinded randomized controlled trials in which researchers directly compared the efficacy of buffered and nonbuffered LAs in adult participants, as well as any associated side effects. Furthermore, they checked the reference lists of all included and excluded studies to identify any further trials. Weighted anesthesia success rates were estimated and compared by using a random-effects model. RESULTS: A total of 14,011 studies were initially identified from the search; 5 double-blinded randomized clinical trials met inclusion criteria. Buffered LAs were more likely to achieve successful anesthesia than nonbuffered LAs (odds ratio, 2.29; 95% confidence interval, 1.11 to 4.71; P = .0232; I2 = 66%). CONCLUSIONS AND PRACTICAL IMPLICATIONS: This investigation revealed that buffered LAs are more effective than nonbuffered LAs when used for mandibular or maxillary anesthesia in pulpally involved teeth. Buffering of LAs has 2.29 times greater likelihood of achieving successful anesthesia.

Anesthetic Considerations for Patients on Antidepressant Therapy-Part I.

Millions of patients take antidepressant medications in the United States for the treatment of depression or anxiety disorders. Some antidepressants are prescribed off-label to treat problems such as chronic pain, low energy, and menstrual symptoms. Antidepressants are a broad and expansive group of medications, but the more common drug classes include tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. A miscellaneous or "atypical" category covers other agents. Some herbal supplements that claim to have antidepressant activity will also be discussed. In Part I of this review, antidepressant pharmacology, adverse effects, and drug interactions with adrenergic agonists will be discussed. In part II, drug interactions with sedation and general anesthetics will be reviewed. Bleeding effects and serotonin syndrome implications in anesthetic practice will also be highlighted.

Phentolamine mesylate for accelerating recovery from lip and tongue anesthesia.

Phentolamine mesylate, at dosages from 0.4 to 0.8 mg in adults and adolescents and at dosages from 0.2 to 0.4 mg in children aged 4 to 11 years, has been proven to be safe and effective for the reversal of soft tissue anesthesia (lip and tongue numbness) and the associated functional deficits resulting from a local dental anesthetic injection containing a vasoconstrictor. Its ability to block a-adrenergic receptors on blood vessels induces vasodilation and enhances the redistribution of the local anesthetic away from the injection site. The low dosages administered for dental local anesthetic reversal in all likelihood accounts for the lack of significant cardiovascular effects that are associated with the medical use of the drug for hypertensive conditions associated with catecholamine excess.

Drug therapy in Alzheimer disease: an update for the oral health care provider.

Alzheimer disease (AD) is a progressive neurologic disorder that manifests as memory loss, personality changes, global cognitive dysfunction, and functional impairment. As the United States population continues to age, the prevalence of AD will rise. Accordingly, oral health care providers will be more likely to treat patients affected by this disease; therefore, it is necessary to understand the pharmacologic agents used for the management of AD. This article provides an update of the available drug therapies for AD and discusses their implications on the oral and dental health of patients.

Hemostatic and anesthetic efficacy of 4% articaine HCl with 1:200,000 epinephrine and 4% articaine HCl with 1:100,000 epinephrine when administered intraorally for periodontal surgery.

BACKGROUND: The objective of this double-masked, randomized, multicenter crossover study was to compare the efficacy of 4% articaine HCl with 1:100,000 epinephrine (A100) to 4% articaine HCl with 1:200,000 epinephrine (A200) for providing effective local anesthesia and hemostasis for periodontal surgery. METHODS: Anesthetic efficacy was based on patient self-report and lack of need for reinjection during the surgical procedures. Hemostatic properties of the formulations were compared using ratings of the surgeons' ability to visualize the surgical field and expectation for bleeding. The volume of blood collected during each surgical session also was measured and compared. RESULTS: Forty-two adult subjects (26 males and 16 females, mean age 46.3 +/- 9.7 years) diagnosed with moderate to severe periodontal disease requiring local anesthesia for matched bilateral periodontal surgery were enrolled and completed the study. Subjects reported satisfactory surgical anesthesia following the A100 and A200 formulations; no supplemental local anesthesia was administered. Significant differences between the A100 and A200 treatments were found for the surgeons' ability to visualize the surgical field (rated as clear 83.3% of the time with A100 and 59.5% of the time with A200; P = 0.008), bleeding expectation (rated as equal to or better than expected 85.7% of the time with A100 and 71.4% of the time with A200; P = 0.034), and volume of blood loss (54.9 +/- 36.0 ml for A100 and 70.2 +/- 53.0 ml for A200; P = 0.018). Sixteen patients experienced 27 mild or moderate adverse events; the most common were postoperative pain (nine patients) and swelling (eight patients). Six adverse events may have been related to treatment. The frequency of adverse events did not vary between formulations. CONCLUSIONS: For patients undergoing periodontal surgery, 4% articaine anesthetic formulations containing epinephrine (1:100,000 or 1:200,000) provided excellent surgical pain control. For patients who can tolerate higher amounts of epinephrine, the 4% articaine 1:100,000 epinephrine formulation had the additional therapeutic advantage of providing better visualization of the surgical field and less bleeding.

Adverse drug interactions involving common prescription and over-the-counter analgesic agents.

BACKGROUND: Eight analgesic preparations with approved indications for acute pain were among the top 200 drugs prescribed in the United States in 2006. In addition, an estimated 36 million Americans use over-the-counter (OTC) analgesics daily. Given this volume of use, it is not surprising that a number of drug interactions involving analgesic drugs have been reported. OBJECTIVES: This article examines the pharmacologic factors that enhance the clinical relevance of potential drug interactions and reviews the literature on drug interactions involving the most commonly used analgesic preparations in the United States. METHODS: A PubMed search was conducted for English-language articles published between January 1967 and July 2007. Among the search terms were drug interactions, acetaminophen, aspirin, ibuprofen, naproxen, celecoxib, NSAIDs, hydrocodone, oxycodone, codeine, tramadol, OTC analgesics, alcohol, ethanol, antihypertensive drugs, methotrexate, warfarin, SSRIs, paroxetine, fluoxetine, sertraline, citalopram, serotonin syndrome, MAOIs, and overdose. Controlled clinical trials, case-control studies, and case reports were included in the review. RESULTS: A number of case reports and well-controlled clinical trials were identified that provided evidence of the relatively well known drug-drug interactions between prescription/OTC NSAIDs and alcohol, antihypertensive drugs, high-dose methotrexate, and lithium, as well as between frequently prescribed narcotics and other central nervous system depressants. In contrast, the ability of recent alcohol ingestion to exacerbate the hepatotoxic potential of therapeutic doses of acetaminophen is not supported by either case reports or clinical research. Use of ibuprofen according to OTC guidelines in patients taking cardioprotective doses of aspirin does not appear to interfere with aspirin's antiplatelet activity, whereas chronic prescription use of ibuprofen and other NSAIDs may interfere. Low-dose aspirin intake appears to abolish the gastroprotective effects of cyclooxygenase-2-selective inhibitors, including celecoxib. There is evidence of other less well known and potentially clinically significant drug-drug interactions, including the ability of selective serotonin reuptake inhibitors to inhibit the analgesic activity of tramadol and codeine through inhibition of their metabolic activation, to induce serotonin syndrome when used chronically in the presence of high doses of tramadol through synergistic serotonergic action, and to increase the potential for gastrointestinal bleeding associated with NSAID therapy through additive or supra-additive antiplatelet activity. CONCLUSIONS: Considering the widespread use of analgesic agents, the overall incidence of serious drug-drug interactions involving these agents has been relatively low. The most serious interactions usually involved other interacting drugs with low therapeutic indices or chronic and/or high-dose use of an analgesic and the interacting drug.

Update on cyclooxygenase inhibitors: has a third COX isoform entered the fray?

It has been more than 30 years since Sir John Vane first reported that the pharmacological actions of aspirin-like drugs could be explained by their ability to inhibit cyclooxygenase (COX). Since then, a second isoform of COX, named COX-2, has been discovered and highly selective inhibitors of this isoform have been marketed. Most recently, a splice variant of COX-1 mRNA, retaining intron 1, and given the names COX-3, COX-1b or COX-1v, has been described. Non-selective NSAIDs such as ibuprofen and naproxen, which inhibit both COX-1 and COX-2, have proven highly effective and safe in the short-term management of acute pain. Highly selective COX-2 inhibitors including celecoxib, rofecoxib, valdecoxib, lumiracoxib, and etoricoxib were developed with the hope of significantly reducing the serious gastrointestinal toxicities associated with chronic high-dose NSAID use. While long-term studies demonstrated that rofecoxib and lumiracoxib reduced the incidence of GI perforations, ulcerations and bleeds by approximately 60% compared to non-selective NSAIDs, recent reports also demonstrated that the chronic use of rofecoxib and celecoxib in arthritis and colorectal polyp patients, and the short-term use of parecoxib and valdecoxib in patients who had undergone coronary artery bypass surgery, resulted in a significant increase in serious cardiovascular events, including myocardial infarction and stroke compared to naproxen or placebo. COX-3 mRNA has been isolated in many tissues including canine and human cerebral cortex, human aorta, and rodent cerebral endothelium, heart, kidney and neuronal tissues. In transfected insect cells, canine COX-3 protein is expressed and was selectively inhibited by acetaminophen. However, in humans and rodents an acetaminophen sensitive COX-3 protein is not expressed because the retention of intron-1 adds 94 and 98 nucleotides to the COX-3 mRNA structure respectively. Since the genetic code is a triplicate code (3 nucleotides to form one amino acid), the retention of the intron in both species results in a frame shift in the RNA message and the production of a truncated protein with a completely different amino acid sequence than COX-1 or COX-2 lacking acetaminophen sensitivity. Advances made through a combination of basic molecular biological and pharmacological techniques, and well designed randomized controlled clinical trials have demonstrated that the apparent gastrointestinal advantage of selective COX-2 inhibitors appears to be outweighed by their potential for cardiovascular toxicity and that acetaminophen's analgesic and antipyretic effects do not involve the inhibition of the COX-1 splice variant protein, putative COX-3.