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PubMed1996

A comparison of 2 analgesic regimens for the control of postoperative periodontal discomfort.

A single blind study of 24 patients compared the postoperative periodontal pain relief and adverse effects associated with a pretreatment regimen with etodolac, a nonsteroidal anti-inflammatory drug (NSAID), to a typical pro re nada (prn) regimen with a combination of acetaminophen with hydrocodone. Patients selected required one or more periodontal osseous surgeries that were judged to involve relatively similar degrees of surgical manipulation. Patients in the etodolac group received two 300 mg capsules 30 minutes prior to surgery and then redosed themselves prn. Patients who received the combination drug were not premedicated and followed a prn regimen. The subjects used a verbal analogue scale to report levels of pain hourly for the first 8 hours (starting 30 minutes prior to surgery) and also indicated any side effects experienced during the first week after surgery. Specific parameters monitored were the mean sum of hourly pain scores, mean hourly pain scores, time to first medication, number of postoperative doses, and adverse effects. Of the parameters studied, the only one that showed a statistically significant difference was the time to first medication. The time span from 30 minutes prior to the beginning of surgery to the first postsurgical dose was greater for etodolac than for the combination drug. However, the total number of medications taken under both regimens was similar. The side effects were minimal for both of the drugs studied. It was concluded that the analgesic regimens tested under clinical practice conditions were comparable in providing analgesia with minimum side effects in uncomplicated periodontal osseous surgery. Studies with larger numbers of patients are needed to definitively address whether these regimens are truly equivalent.

Acetaminophen↗
PubMed2000

The antitussive activity of delta-opioid receptor stimulation in guinea pigs.

In this study, the activity of the delta-opioid receptor subtype-selective agonist, SB 227122, was investigated in a guinea pig model of citric acid-induced cough. Parenteral administration of selective agonists of the delta-opioid receptor (SB 227122), mu-opioid receptor (codeine and hydrocodone), and kappa-opioid receptor (BRL 52974) produced dose-related inhibition of citric acid-induced cough with ED(50) values of 7.3, 5.2, 5.1, and 5.3 mg/kg, respectively. The nonselective opioid receptor antagonist, naloxone (3 mg/kg, i.m.), attenuated the antitussive effects of codeine or SB 227122, indicating that the antitussive activity of both compounds is opioid receptor-mediated. The delta-receptor antagonist, SB 244525 (10 mg/kg, i.p.), inhibited the antitussive effect of SB 227122 (20 mg/kg, i.p.). In contrast, combined pretreatment with beta-funaltrexamine (mu-receptor antagonist; 20 mg/kg, s.c.) and norbinaltorphimine (kappa-receptor antagonist; 20 mg/kg, s.c.), at doses that inhibited the antitussive activity of mu- and kappa-receptor agonists, respectively, was without effect on the antitussive response of SB 227122 (20 mg/kg, i.p.). The sigma-receptor antagonist rimcazole (3 mg/kg, i.p.) inhibited the antitussive effect of dextromethorphan (30 mg/kg, i.p.), a sigma-receptor agonist, but not that of SB 227122. These studies provide compelling evidence that the antitussive effects of SB 227122 in this guinea pig cough model are mediated by agonist activity at the delta-opioid receptor.

Animals↗
PubMedDate not supplied

Management of cough in advanced cancer.

Cough is a common symptom in cancer, with causes that can be benign or malignant. When severe, it affects patients' quality of life and well being. Treatment begins with a detailed history and careful physical examination, followed by chest imaging. Managing cough is directed at correcting the reversible causes. Empiric treatment of cough is valuable in both reversible and irreversible causes. We prefer hydrocodone as first-line empiric treatment, but when the cough is resistant to this, our second-line therapy would be the addition or substitution of benzonatate. Bronchodilators, as well as corticosteroids, are commonly employed in our practice and can be useful in unsuspected bronchospasm.

Adrenal Cortex Hormones↗
PubMed1981

An evaluation of the analgesic efficacy of three opioid-analgesic combinations in postoperative oral surgery pain.

The analgesic efficacy of a hydrocodone-acetaminophen combination, a codeine-acetaminophen combination, a codeine-APC (aspirin, phenacetin, and caffeine) combination, and a placebo was evaluated in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Each of the active medications had a significant effect on essentially all measures of total and peak analgesia; they did not differ significantly on any measure of analgesia. Adverse effects were transitory and, in general, appear to have been related to the centrally acting component of each combination analgesic.

Acetaminophen↗
PubMed1981

Aspirin and acetaminophen as constituents of analgesic combinations.

Aspirin and acetaminophen are the mainstays of oral analgesic combinations. One group of combinations is composed of antipyretic-analgesics combined with each other. The superior efficacy of such combinations as compared with an optimal dose of one of the constituents remains to be proved, and there is little evidence that such combinations have less adverse-effect liability than a single agent. On the other hand, there is substantial evidence that combinations of an optimal dose of aspirin or acetaminophen with a narcotic (eg, codeine, hydrocodone, or oxycodone) produce an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equianalgesic dose of a single constituent.

Acetaminophen↗
PubMed2005

Rates of abuse of tramadol remain unchanged with the introduction of new branded and generic products: results of an abuse monitoring system, 1994-2004.

PURPOSE: The analgesic Tramadol HCl (Ultram) was approved in 1994 as a non-scheduled drug under the CSA provided that a novel risk-management program would be developed by an Independent Steering Committee (ISC). The risk-management program began in 1995 with the launch of Ultram, and has been modified over the past decade to accommodate Ultracet (Ultram and acetaminophen) in 2001 and generic tramadol in 2002. This provided a unique opportunity to study the potential changes in abuse as the generic and combination products became available. METHODS: To proactively detect cases of abuse and diversion, the ISC developed a comprehensive questionnaire which was completed quarterly by an extensive network of drug abuse experts (n = 309) and police agencies (n = 100) who were asked to indicate how many diversion cases involving Ultram, Ultracet, and generic tramadol were identified during the preceding 3 months and what were the ten most commonly diverted drugs in their catchment area during that period. RESULTS AND CONCLUSIONS: The data generated demonstrate that the abuse of tramadol remained very low despite new branded and generic formulations. Contrary to the hypothesis that cheaper generic drugs would lead to higher rates of abuse, we found no increase in abuse with the introduction of generic tramadol. Ultracet abuse rates, unlike those found with other widely used hydrocodone and oxycodone combination products, have been even lower than that observed for tramadol. Since the FDA has now mandated that proactive risk-management plans be implemented for new drugs, the tramadol risk-management plan may be useful as a prototypic model which can be modified to accommodate other drugs with abuse potential.

Acetaminophen↗
PubMed2001

Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.

INTRODUCTION: Management of posthemorrhoidectomy pain remains a very unsatisfactory clinical dilemma. Compared with electrocautery and laser, the Harmonic Scalpel causes minimal lateral thermal injury during tissue dissection. PURPOSE: The aim of the study was to establish whether decreased lateral thermal injury translated into diminished posthemorrhoidectomy pain. METHODS: A prospective randomized trial comparing Harmonic Scalpel hemorrhoidectomy and electrocautery was undertaken. Fifty consecutive patients were randomized into two groups: Harmonic Scalpels and electrocautery hemorrhoidectomy. The indications included Grade III internal hemorrhoids with external components or Grade IV disease. Patients with additional anorectal pathology (fissure or fistula) were excluded, as were patients with neurologic deficits, chronic pain syndrome, and those already taking narcotic analgesics. Pain was assessed using a visual analog scale preoperatively and on postoperative Days 1, 2, 7, 14, and 28. Twenty-four-hour narcotic usage (Hydrocodone, 10 mg) was recorded on postoperative Days 1, 2, 7, 14, and 28. A three-quadrant modified Ferguson hemorrhoidectomy was performed with each patient in the prone jackknife position. RESULTS: Pain in the Harmonic Scalpel hemorrhoidectomy group was significantly less than in electrocautery patients on each postoperative day studied. Analgesic requirements were also significantly less in the Harmonic Scalpel group on Days 1, 2, 7, and 14. There was no correlation between postoperative pain and grade of hemorrhoid, status of the surgical incision (open vs. closed), or any other study variable. Fifty-five percent of Harmonic Scalpel patients returned to work within one week of surgery, compared with 23 percent of electrocautery patients. CONCLUSION: The study demonstrates significantly reduced postoperative pain after Harmonic Scalpel hemorrhoidectomy compared with electrocautery controls. The diminished postoperative pain in the Harmonic Scalpel group likely results from the avoidance of lateral thermal injury.

Adult↗
PubMed2001

Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerin ointment on pain after hemorrhoidectomy.

PURPOSE: Fissure-in-ano is characterized by pain, bleeding, and internal anal sphincter hypertonicity. Spasm of the internal sphincter also plays a role in hemorrhoidal disease and may be a source of anal pain after hemorrhoid surgery. Inducing sphincter relaxation with a nitroglycerin ointment has shown promise in healing anal fissures and relieving symptoms of pain. Our study attempts to test the hypothesis that topical nitroglycerin applied to the perianal region is beneficial in reducing pain after hemorrhoidectomy. METHODS: After hemorrhoidectomy 39 patients were randomly assigned to receive 0.2 percent nitroglycerin ointment (n = 19) or placebo (n = 20). Ointments were applied to the perianal region three times daily for seven days. Patients were prescribed hydrocodone bitartrate to take as needed. Visual analog scales were used to measure postoperative pain intensity and ointment benefits. Patients completed questionnaires to record medication morbidity and number of prescribed or nonprescribed medications taken. RESULTS: Patients using nitroglycerin had less pain and greater benefit from ointment than those did in the placebo group, but differences were not significant. Narcotic use was higher in the placebo group when considered on a daily basis, but was statistically significant on the second postoperative day only (P < 0.05). Morbidity from ointment application was significantly higher in the nitroglycerin group (P < 0.002) and included a headache in 8 of 19 patients. Nonsteroidal anti-inflammatory drugs and acetaminophen were not prescribed, but were taken more frequently in nitroglycerin patients (P < 0.0003). CONCLUSION: Perianal application of 0.2 percent nitroglycerin ointment after hemorrhoidectomy significantly reduced narcotic requirements on the second postoperative day. Headaches and a subsequent need for nonnarcotic medications may limit benefits of nitroglycerin.

Administration, Topical↗
PubMed1994

Local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy in the management of patients with chronic pancreatitis.

UNLABELLED: OPERATION: Local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy of the body and tail of the pancreas (LR-LPJ) was designed to improve decompression of the head of the pancreas, which often was not drained well by standard longitudinal pancreaticojejunostomy. This was achieved by excising the head of the pancreas overlying the ducts of Wirsung and Santorini, and duct to the uncinate, along with their tributary ducts. PATIENT MATERIAL: The operation has been performed on 50 patients. There were five late deaths among the 50 patients; two at 6 months, and one each at 24, 26, and 91 months. Eighty percent of the patients were alcoholics, 50% had pseudocysts, and 80% had calcification. ASSESSMENT: Pain was assessed on a scale of 1 to 10, with 10 being most severe. Narcotic intake was considered minimal-Vicodin equivalent (hydrocodone bitartate, 5 mg, acetaminophen, 500 mg; Vicodin, Knoll Pharmaceuticals, Whippany, NJ) once or twice/month; moderate--Vicodin weekly daily; and major--meperidine hydrochloride (Demerol, Winthrop Pharmaceuticals, New York, NY) weekly or daily. RESULTS: Pain relief in 47 patients was excellent (74.5%), improved in 12.75%, and unimproved in 12.75%. Endocrine status in 45 patients was as follows: 69% were not diabetic, and 20% were diabetic preoperatively and postoperatively. Postoperatively, 11% had progression of their diabetes. Exocrine function was not worsened and may have been improved in some patients. Sixty-four percent of 39 patients gained an average of 15.3 pounds. Fifty-nine percent of patients were not working preoperatively or postoperatively. CONCLUSIONS: The LR-LPJ provides good pain relief with a modest increase in endocrine and exocrine insufficiency and a significant increase in weight. Even when relieved of pain, patients seldom return to the work force.

Adult↗
PubMed2004

Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing.

INTRODUCTION: Oral metronidazole has been previously demonstrated to decrease postoperative pain after open diathermy hemorrhoidectomy. The current study investigates the efficacy of topical metronidazole (10 percent) in reducing postoperative pain and promoting wound healing after Harmonic Scalpel hemorrhoidectomy. METHODS: A prospective, randomized trial was conducted to compare posthemorrhoidectomy pain and wound healing with use of topical metronidazole (10 percent) vs. placebo carrier, applied to the surgical site. Surgical indications included grade 3 or 4 internal or external hemorrhoidal disease, with or without a fissure-in-ano. Pain was assessed using a visual analog score (VAS) preoperatively and on postoperative days 1, 2, 7, 14, and 28. Twenty-four-hour narcotic use (hydrocodone 10 mg) was recorded on postoperative days 1, 2, 7, 14, and 28. Digital photographs of the surgical site were taken at 14 days postoperatively. The photographs were independently ranked by three blinded observers according to a) postoperative edema, b) primary vs. secondary healing, and c) overall wound healing. RESULTS: Twenty patients were randomized in a prospective manner, ten to the topical 10 percent metronidazole group and ten to the placebo carrier group. Patients in the topical metronidazole group experienced significantly less postoperative pain at day 7 (VAS +/- SEM, 3.4 +/- 0.4 vs. 6.3 +/- 0.5; P = 0.002) and day 14 (1.0 +/- 0.4 vs. 3.2 +/- 0.7, P = 0.02). There was no statistical difference in narcotic analgesic requirements between groups. In the metronidazole group, postoperative edema was ranked significantly lower (mean score, 3.0 vs. 7.0, P < 0.01) and overall wound healing ranked significantly better (4.0 vs. 7.0, P = 0.03) than in controls. CONCLUSION: Topical 10 percent metronidazole significantly reduces posthemorrhoidectomy discomfort at days 7 and 14 postoperatively. Postoperative edema is reduced and overall healing is improved, compared with that of carrier controls.

Administration, Topical↗
PubMed2005

A randomized, prospective, double-blind, placebo-controlled trial of the effect of a calcium channel blocker ointment on pain after hemorrhoidectomy.

PURPOSE: Spasm of the internal sphincter plays a role in hemorrhoidal disease and may be a source of anal pain after hemorrhoid surgery. We have evaluated the effects of topical diltiazem, a calcium channel blocker, in reducing pain after hemorrhoidectomy. METHODS: After hemorrhoidectomy, 18 patients were randomly assigned to receive 2 percent diltiazem ointment (n = 9) or a placebo ointment (n = 9). Ointments were applied to the perianal region three times daily for seven days. Patients were prescribed hydrocodone bitartrate (Vicodin) to take as needed. The type and number of prescribed or nonprescribed medications taken during the postoperative period were recorded. Patients maintained a log to measure postoperative pain daily and perceived benefit of the ointment, using a Visual Analog Scale ranging from 0 to 10. Any postoperative morbidity noted during the follow-up period was recorded. RESULTS: Patients using the diltiazem ointment had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week. Postoperative pain scores in the placebo group averaged 8.8 +/- 1.2 early and diminished to 5.2 +/- 1.7 at the end of one week, compared to the diltiazem group of 5.2 +/- 2.4 early and 2.3 +/- 1.2 at the end of one week (P < 0.001, both time periods). Perceived benefit in the placebo group averaged 2.7 +/- 1.2 vs. 5.6 +/- 1.4 in the diltiazem group (P < 0.001). Total and daily narcotic use was higher in the placebo group, but this was not statistically significant (P = 0.13). No differences in the frequency of use of nonsteroidal anti-inflammatory drugs and acetaminophen were seen between the two groups, and there were no differences in morbidity between the two groups. CONCLUSIONS: Perianal application of 2 percent diltiazem ointment after hemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial, with no increase in associated morbidity. Patients using a placebo ointment tend to take more prescription narcotics for pain relief postoperatively, with a similar usage of nonsteroidal anti-inflammatory drugs and acetaminophen, although differences were not significant.

Administration, Topical↗
PubMed1996

Determination of illicit drugs and related substances by high-performance liquid chromatography with an electrochemical coulometric-array detector.

A general method for the simultaneous determination of fifteen common drugs (6-acetylmorphine, 3,4-methylenedioxymetamphetamine, buprenorphin, cocaine, codeine, dihydrocodeine, ethylmorphine, heroin, hydrocodone, lidocaine, methadone, morphine, naloxone, procaine and thebaine) was developed using reversed-phase HPLC and electrochemical detection. The separation of the drugs was achieved by using as the mobile phase 20 mM monobasic sodium phosphate-acetonitrile (90:10) with a gradient to 50% of the organic modifier, on a silica based C18 column (150 x 4.6 mm I.D.) of 3 microns particle size and by the selectivity supplied by an array of eight coulometric electrodes at increasing potential. It was possible to identify and to determine fifteen different drugs in the same chromatographic run in 50 min. The method was tentatively applied to the determination of drugs in extracts of human hair.

Chromatography, High Pressure Liquid↗
PubMed1991

Mu receptor binding of some commonly used opioids and their metabolites.

The binding affinity to the mu receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with 3H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding (e.g. morphine-6-glucuronide Ki = 0.6 nM; morphine = 1.2 nM). Decreasing the length of the alkyl group at position 3 decreased the Ki values (morphine less than codeine less than ethylmorphine less than pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 (e.g. hydrocodone, Ki = 19.8 nM) had relatively weak receptor binding, whilst their O-demethylated metabolites (e.g. hydromorphone, Ki = 0.6 nM) had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

Animals↗
PubMed1990

Influence of polarity on dose-response relationships of intrathecal opioids in rats.

Dose-response curves were constructed for intrathecal morphine (M), oxymorphone (OM), hydromorphone (HM), diamorphine (DM), 14-hydroxydihydromorphine (OHM), oxycodone (OC), hydrocodone (HC) and fentanyl (F). Intrathecal catheters were placed in 69 rats under halothane/N2O anaesthesia. After recovery, baseline hot plate and tail flick latencies were measured, and a dose of opioid was given. Hot plate and tail flick latencies were assessed at 5, 15, 30, 60, 90, 120 min and then hourly until they returned to within 25% of baseline. Response latencies were converted to per cent of maximum possible effect (% MPE) and the area under the % MPE X time curve was taken as the response. This measure includes information about both potency and duration of action. Each rat received 3 opioids and saline at intervals of 2-3 days. On a fifth occasion, the animal's first treatment was repeated. Each opioid was studied over an 8-fold dose range. Results of both hot plate and tail flick were best described by a model including log(dose), a component due to development of tolerance over the 5 experimental days, and an among-rat variation term. In the hot plate test, doses equieffective in producing a response (AUC) over the dose range studied were in the order OHM less than OM less than HM less than M less than F less than DM less than HC less than OC. Slopes of the log(dose)-response curves were similar for all drugs except OHM, which had a steeper slope. A model is proposed in which hot plate and tail flick latencies are prolonged while CSF concentrations of a drug are above its minimum effective concentration, and drug is cleared from the CSF by a first-order process, possibly uptake into the spinal cord and removal via the blood. This model predicts that log(dose)-response curves will be linear, as was observed, with slopes inversely proportional to the rate constant for clearance from CSF. According to this model the steeper slope of the OHM log(dose)-response may be interpreted as indicating slower clearance from CSF. OHM has the lowest octanol/pH 7.4 buffer distribution coefficient (0.34) of all opioids studied, possibly leading to a lower rate of uptake into the spinal cord.

Animals↗
PubMed1992

Postherpes simplex type 1 neuralgia simulating postherpetic neuralgia.

Patients with prodromal neuralgia associated with recurrent herpes simplex type 1 (HST1) infection and chronic facial pain following years of relapsing HST1 have been described. Chronic neuralgia following a single clinical HST1 infection and simulating postherpetic neuralgia has not been previously reported. Such a case is described: A 49-yr-old woman with a 2-mo history of oral-facial dyskinesia developed burning pain and hypersensitivity of the left side of the tongue, lower gum, and inner cheek, followed 1 day later by a vesicular rash in the same painful distribution. Viral cultures of the lesions identified HST1 but not herpes zoster. Cerebrospinal fluid analyses during the vesicular lesion stage and 1 mo later were normal with no viral growth. Oral and facial lesions resolved after 10 days; acyclovir was given for 3 wk. Brain and brainstem magnetic resonance imaging (MRI), electroencephalogram, and brainstem evoked potential studies were normal. Hyperesthesias, allodynia, and burning pain persisted despite nonsteroidal antiinflammatory agents, codeine and hydrocodone. Oral opioids were administered until sedation occurred, with no relief of pain. The burning pain and hyperesthesia resolved after the 16th day of amitriptyline use, 75 mg/day. A trial off amitriptyline 6 mo later resulted in recurrence of pain, and amitriptyline was restarted with good pain control. Post-HST1 neuralgia may simulate postherpetic neuralgia clinically, and painful symptoms may respond to amitriptyline.

Amitriptyline↗
PubMed1995

Effect of preincision versus postincision infiltration with bupivacaine on postoperative pain.

STUDY OBJECTIVE: To compare the efficacy of preincision wound infiltration with bupivacaine to wound infiltration at the end of the operation. DESIGN: A prospective, randomized, double-blind study. SETTING: University medical center. PATIENTS: 56 ASA status I and II women scheduled for abdominal hysterectomy were randomly assigned to one of three treatment groups. INTERVENTIONS: Group 1 (control) received no local anesthetic infiltration. Group 2 received subcutaneous infiltration with 40 ml of bupivacaine 0.5% (pH 6.9) 15 minutes prior to incision. Group 3 received wound infiltration with a similar solution at the end of surgery. Anesthesia was induced with thiopental 3.0 mg/kg i.v., droperidol 50 micrograms/kg i.v., and sufentanil 0.5 microgram/kg i.v. and maintained with nitrous oxide 67% in oxygen and sufentanil 0.1 microgram/kg IV boluses as required. Postoperative pain was treated with morphine via a patient-controlled analgesia delivery system for 24 hours, followed by oral hydrocodone for 3 days. MEASUREMENTS AND MAIN RESULTS: The opioid consumption was recorded for 4 days postoperatively. Pain scores were measured at 4 to 8-hour intervals using 100 mm visual analog scales. There was no difference in either the opioid analgesic requirements or the pain scores between the three study groups. CONCLUSIONS: Wound infiltration, either preincision or postincision, had no clinically significant effect on the pain scores or analgesic requirements following abdominal hysterectomy.

Adult↗
PubMed2006

Analgesic efficacy of perioperative celecoxib in ambulatory arthroscopic knee surgery: a double-blind, placebo-controlled study.

PURPOSE: To examine whether celecoxib, administered perioperatively, reduces opioid consumption and opioid-related adverse effects, and provides effective analgesia, in patients undergoing ambulatory arthroscopic knee meniscectomy. METHODS: Patients (> or = 18 years) with diagnosed knee meniscus disease were given celecoxib (400 mg; n = 99) or placebo (n = 101) 1 hour before they underwent arthroscopic knee surgery; this was followed by celecoxib (200 mg) or placebo given postoperatively at their first request for pain medication. Surgery was performed with patients under general anesthesia (fentanyl, 1 to 3 microg/kg plus 0.25% intra-articular bupivacaine, 10 to 20 mL) administered at the index joint. Every 4 to 6 hours, patients were allowed 1 to 2 tablets of hydrocodone bitartrate 5 mg/acetaminophen 500 mg (and optional opioids as needed). All efficacy analyses were conducted in the modified intent-to-treat population. RESULTS: In the 24 hours following surgery, total opioid consumption was significantly reduced in the celecoxib group (3.6 tablets) compared with the placebo group (4.6 tablets; P = .009). Celecoxib was associated with significant reductions in opioid consumption compared with placebo at 10 to 12 hours (P = .005) and at 12 to 24 hours (P = .012). The percentage of placebo-treated patients (41%) who required opioid analgesics was significantly greater than the percentage of celecoxib-treated patients who required opioids (22%; P = .008) at 10 to 12 hours. Adverse events (AEs) were experienced by more patients in the placebo group (37%) than in the celecoxib group (18%). Incidences of opioid-related events, such as central nervous system disorders (12% v 3%, respectively) and constipation (5% v 1%, respectively), were higher in placebo-treated patients than in those given celecoxib. CONCLUSIONS: Perioperative administration of celecoxib plus optional opioids reduces the use of opioids and the occurrence of opioid-related AEs compared with treatment with placebo plus optional opioids given to patients undergoing arthroscopic knee meniscectomy. LEVEL OF EVIDENCE: Level I, randomized, double-blind, placebo-controlled, parallel-group study.

Adult↗
PubMed2006

The effect of opiates on the activity of human placental aromatase/CYP19.

Aromatase, cytochrome P450 19, is a key enzyme in the biosynthesis of estrogens by the human placenta. It is also the major placental enzyme that metabolizes the opiates L-acetylmethadol (LAAM), methadone, and buprenorphine (BUP). Methadone and BUP are used in treatment of the opiate addict and are competitive inhibitors of testosterone conversion to estradiol (E(2)) and 16alpha-hydroxytestosterone (16-OHT) to estriol (E(3)) by aromatase. The aim of this investigation is to determine the effect of 20 opiates, which can be administered to pregnant patients for therapeutic indications or abused, on E(2) and E(3) formation by placental aromatase. Data obtained indicated that the opiates increased, inhibited, or had no effect on aromatase activity. Their effect on E(3) formation was more pronounced than that on E(2) due to the lower affinity of 16-OHT than testosterone to aromatase. The K(i) values for the opiates that inhibited E(3) formation were sufentanil, 7 +/- 1 microM; LAAM, 13 +/- 8 microM; fentanyl, 25 +/- 5 microM; oxycodone, 92 +/- 22 microM; codeine, 218 +/- 69 microM; (+)-pentazocine, 225 +/- 73 microM. The agonists morphine, heroin, hydromorphone, oxymorphone, hydrocodone, propoxyphene, meperidine, levorphanol, dextrorphan, and (-)-pentazocine and the antagonists naloxone and naltrexone caused an increase in E(3) formation by 124-160% of control but had no effect on E(2) formation. Moreover, oxycodone and codeine did not inhibit E(2) formation and the IC(50) values for fentanyl, sufentanil, and (+)-pentazocine were >1000 microM. It is unlikely that the acute administration of the opiates that inhibit estrogen formation would affect maternal and/or neonatal outcome. However, the effects of abusing any of them during the entire pregnancy are unclear at this time.

Aromatase↗