Celebrex for Pain Relief After Oral Surgery
Celebrex for Pain Relief After Oral Surgery
This study will evaluate the effects of the new anti-inflammatory drug, Celebrex, on
 relieving pain after oral surgery. It is also designed to assess the drug's selective
 inhibition of a chemical called cyclooxygenase-2 and not its closely related form,
 cyclooxygenase-1. This selective inhibition allows pain alleviation without the adverse side
 effects (e.g., bleeding and stomach upset) often associated with anti-inflammatory drugs.

 Healthy volunteers who require removal of their third molars are eligible for this study.
 Participants will have oral surgery for tooth extraction after receiving a local anesthetic
 (lidocaine) in the mouth and a sedative (midazolam) through an arm vein. On the evening
 before and 1 hour before surgery, patients will be given a dose of either the standard
 anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or Celebrex, or a placebo (a pill
 with no active ingredient). After surgery, a small piece of tubing will be placed in each
 extraction site and tied to an adjacent tooth to hold it in place. Samples will be collected
 from the tubing to measure chemicals involved in pain and inflammation. Patients will stay in
 the clinic for up to 6 hours after surgery while the anesthetic wears off and will complete
 pain questionnaires. During that time, they may receive acetaminophen plus codeine (Tylenol
 3), if needed, for pain. The tubing then will be removed and the patient discharged with
 standard pain medication.
Prostanoids are mediators that have been implicated in all stages of inflammation. The
 inhibition of prostanoid synthesis by NSAIDs forms the basis of their therapeutic as well as
 side effects. NSAIDs directly inhibit cyclooxygenase [COX], which leads to reduction of
 prostaglandin synthesis and also to gastric erosions, inhibition of platelet aggregation and
 nephrotoxicity. The identification of the two isoforms of COX lead to the hypothesis that
 COX-2 is responsible for the production of prostaglandins following tissue injury, while
 COX-1 is involved in normal homeostasis.

 The selective COX-2 inhibitors are believed to be efficacious anti-inflammatory drugs devoid
 of the side effects associated with the inhibition of COX-1. However, the selectivity of
 these drugs has only been demonstrated in vitro and ex vivo, which may not be a reliable
 indicator of the in vivo selectivity. The proposed study aims to evaluate the in vivo
 selectivity of celecoxib, a drug demonstrated to be a selective inhibitor of COX-2 in vitro
 in the oral surgery model of acute inflammation.
INCLUSION CRITERIA:

 Healthy volunteers between the ages of 18-65 years.

 Patients will be eligible for this study if the two mandibular molars are classified as
 partial or full bony impactions.

 EXCLUSION CRITERIA:

 Patients who are allergic to sulfa-drugs.

 Patients who have had asthma, hives or an allergic reaction to aspirin, ibuprofen or any
 similar drugs.

 Patients with gastrointestinal ulcers or a history of gastrointestinal bleeding.

 Patients who are pregnant or nursing.

 Patients of infection or inflammation [pericoronitis] at either extraction site.

 Patients with severe kidney disease.

 Patients who are taking any of the following drugs: anti-depressants, diuretics, aspirin on
 a near daily basis, coumadin or other blood thinners.

 Patients who are taking drugs known to inhibit P450 2C9 and drugs metabolized by P450 2D6.