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PubMedDate not supplied

Photodynamic therapy for Barrett's esophagus and high grade dysplasia: results of a patient satisfaction survey.

There are few data available describing the experience of patients who have undergone photodynamic therapy with porfimer sodium for Barrett's esophagus. We describe the results of a satisfaction survey reported by 16 of 18 patients (11 men, 5 women; median age 75 years; median response at 27 months after treatment) treated with photodynamic therapy for Barrett's esophagus with high-grade dysplasia. Treatments were performed on an outpatient basis although two patients required clinic visits for intravenous fluids. Subjects reported their most significant post-treatment problem was odynophagia or dysphagia (75%), which was best treated with a hydrocodone bitartrate and acetaminophen elixir (75%). Cutaneous photosensitivity persisted for a median of six weeks; two patients had phototoxic reactions requiring clinic evaluation and treatment. All but two patients reported swallowing problems lasting a median of four weeks, and weight loss (median 6.8 kg). All patients indicated they would again choose photodynamic therapy if they were faced with a similar choice of endoscopic treatment versus surgery for Barrett's esophagus with high-grade dysplasia. These results indicate a generally high level of satisfaction in patients who have been treated with porfimer sodium photodynamic therapy for Barrett's esophagus with high-grade dysplasia.

Aged↗
PubMed1997

Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence.

Oral opiates (e.g. codeine, oxycodone, and hydrocodone) are metabolized by cytochrome CYP2D6 to metabolites of increased activity (e.g. morphine, oxymorphone and hydromorphone). CYP2D6 is genetically polymorphic, 4-10% of Caucasians lack CYP2D6 activity (poor metabolizers) due to inheritance of two non-functional alleles. We tested whether the failure to activate oral opiates was a protection factor in opiate dependence by genotyping (CYP2D6*3 and CYP2D6*4 defective mutant alleles) caucasians who met or didn't meet DSM criteria for oral opiate dependence. In opiate (+/- smoking) dependent subjects we found no poor metabolizers. In contrast, the poor metabolizer frequency in never-dependent control and multi-drug dependent comparison groups was 4% and 6.5%, respectively. This under-representation of poor metabolizers (Fisher's exact test, p < or = 0.05) in people dependent on oral opiates suggests that the CYP2D6 defective genotype is a pharmacogenetic protection factor for oral opiate dependence (estimated odds ratio > 7). This is the first investigation and demonstration of differences in genetically determined P450 metabolism influencing risk for substance dependence and we suggest that these differences may influence the risk for dependence of other substrate drugs, and may occur with other genetically variable P450s.

Administration, Oral↗
PubMed2005

Recent trends in narcotic deaths.

The prevalence of overdose deaths from opioids is still generally increasing throughout the world. Heroin is still the predominant illicit opioid of interest to toxicology laboratories because of its continuing widespread availability and its ability to elicit respiratory depression and coma. In many countries methadone continues to play a major role in cases of drug toxicity because of its large-scale use to treat opioid dependency and its high potency and long duration of action. Increasingly, buprenorphine is being used as an alternative pharmacotherapy, and although apparently safer than methadone, it still has an inherent risk of toxicity when used with CNS depressants such as benzodiazepines or when injected. Morphine continues to be the dominant analgesic; however, oxycodone, hydromorphone, hydrocodone, and fentanyl are increasingly being used and will require increasing efforts by toxicology laboratories to ensure that these substances are adequately covered by testing programs.

Humans↗
PubMed2004

Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl from transdermal patches.

The transdermal fentanyl system delivers a specific dose at a constant rate. Even after the prescribed application time has elapsed, enough fentanyl remains within a patch to provide a potentially lethal dose. Death due to the intravenous injection of fentanyl extracted from transdermal patches has not been previously reported. We present 4 cases in which the source of fentanyl was transdermal patches and was injected. In all of these cases, the victim was a white male who died at home. Case 1 was a 35-year-old with no known history of drug use, who was found by his wife on the floor of his workshop. Police recovered a fentanyl patch, needle, and syringe at the scene. Case 2 was a 38-year-old with a known history of drug use whose family claimed that he was in a treatment program that used fentanyl patches for unknown reasons. His brother found him dead in bed, and law enforcement officers found a hypodermic needle beside the body; a ligature around his left hand, and apparent needle marks between his first and second digits were also noted. Case 3 was a 42-year-old with a recent attempted suicide via overdose who was found dead at his home. An empty box of fentanyl patches, Valium, Ritalin, and 2 syringes were found at the scene. Case 4 was a 39-year-old found by his mother, who admitted to removing a needle with attached syringe from the decedent's arm. Medications at the scene included hydrocodone, alprazolam, zolpidem, and fentanyl patches. All reported deaths were attributed to fentanyl intoxication, with blood concentrations ranging from 5 to 27 microg/L.

Administration, Cutaneous↗
PubMed2004

Persistent nonmalignant pain and analgesic prescribing patterns in elderly nursing home residents.

OBJECTIVES: To determine the prevalence of analgesics used, their prescribing patterns, and associations with particular diagnoses and medications in patients with persistent pain. DESIGN: Cross-sectional study. SETTING: Nursing homes from 10 U.S. states. PARTICIPANTS: A total of 21,380 nursing home residents aged 65 and older with persistent pain. MEASUREMENTS: Minimum Data Set (MDS) assessments on pain, analgesics, cognitive, functional, and emotional status were summarized. Logistic regression models identified diagnoses associated with different analgesic classes. RESULTS: Persistent pain as determined using the MDS was identified in 49% of residents with an average age of 83; 83% were female. Persistent pain was prevalent in patients with a history of fractures (62.9%) or surgery (63.6%) in the past 6 months. One-quarter received no analgesics. The most common analgesics were acetaminophen (37.2%), propoxyphene (18.2%), hydrocodone (6.8%), and tramadol (5.4%). Only 46.9% of all analgesics were given as standing doses. Acetaminophen was usually prescribed as needed (65.6%), at doses less than 1,300 mg per day. Nonsteroidal antiinflammatory drugs (NSAIDs) were prescribed as a standing dose more than 70% of the time, and one-third of NSAIDs were prescribed at high doses. CONCLUSION: In nursing home residents, persistent pain is highly prevalent, there is suboptimal compliance with geriatric prescribing recommendations, and acute pain may be an important contributing source of persistent pain. More effective provider education and research is needed to determine whether treatment of acute pain could prevent persistent pain.

Activities of Daily Living↗
PubMed2006

Changing patterns of drug and alcohol use in fatally injured drivers in Washington State.

We have previously reported on patterns of drug and alcohol use in fatally injured drivers in Washington State. Here we revisit that population to examine how drug use patterns have changed in the intervening 9 years. Blood and serum specimens from drivers who died within 4 h of a traffic accident between February 1, 2001, and January 31, 2002, were analyzed for illicit and therapeutic drugs and alcohol. Drugs when present were quantitated. Samples suitable for testing were obtained from 370 fatally injured drivers. Alcohol was detected above 0.01 g/100 mL in 41% of cases. The mean alcohol concentration for those cases was 0.17 g/100 mL (range 0.02-0.39 g/100 mL). Central nervous system (CNS) active drugs were detected in 144 (39%) cases. CNS depressants including carisoprodol, diazepam, hydrocodone, diphenhydramine, amitriptyline, and others were detected in 52 cases (14.1%), cannabinoids were detected in 47 cases (12.7%), CNS stimulants (cocaine and amphetamines) were detected in 36 cases (9.7%), and narcotic analgesics (excluding morphine which is often administered iatrogenically in trauma cases) were detected in 12 cases (3.2%). For those cases which tested positive for alcohol c. 40% had other drugs present which have the potential to cause or contribute to the driver's impairment. Our report also considers the blood drug concentrations in the context of their interpretability with respect to driving impairment. The data reveal that over the past decade, while alcohol use has declined, some drug use, notably methamphetamine, has increased significantly (from 1.89% to 4.86% of fatally injured drivers) between 1992 and 2002. Combined drug and alcohol use is a very significant pattern in this population and is probably overlooked in DUI enforcement programs.

Accidents, Traffic↗
PubMed1999

Transformations of codeine to important semisynthetic opiate derivatives by Pseudomonas putida m10.

A biotransformation mixture which contained codeine and washed cells of Pseudomonas putida M10 gave rise to a number of transformation products that are of clinical importance which included hydrocodone, dihydrocodeine and 14beta-hydroxycodeine. Incubations with the same organism and codeinone gave rise to 14beta-hydroxycodeinone and 14beta-hydroxycodeine. Cell-free extracts and membrane fractions of P. putida M10 were shown to catalyse the 14beta-hydroxylation of codeinone. In addition, the potent analgesic oxycodone was shown to be produced from 14beta-hydroxycodeinone.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Sedative drug requirements during flexible bronchoscopy.

BACKGROUND: There is a paucity of data comparing doses of sedative medication during bronchoscopy in immunosuppressed and non-immunosuppressed patients. OBJECTIVES: The aim of this study was to define the sedative medication doses used in specific patient groups during bronchoscopy. METHODS: Bronchoscopy was performed under local anesthesia, sedation with intermittent boluses of intravenous midazolam and intravenous hydrocodone 5 mg. Two hundred and thirty-nine consecutive bronchoalveolar lavage procedures were included. Procedures in non-immunosuppressed patients were classified as controls (n = 91). Procedures in immunosuppressed patients who received midazolam consisted of stem cell transplant (34), solid organ transplant (25), chemotherapy (33), HIV with drug abuse (10), HIV (5), prednisone (17) and immunosuppression for other diseases (12). Intravenous propofol was administered during 12 procedures due to inability to achieve optimal sedation with midazolam in a previous bronchoscopy (stem cell transplant recipient 1, lung transplant for cystic fibrosis 5) and during the same bronchoscopy due to inadequate sedation with a high dose of midazolam--renal transplant recipient 1, drug abuse (HIV 1, renal transplant recipient 1), bronchoscopy combined with gastroscopy (2) and a hypoxemic patient (1). The mean dose of propofol administered was 2.8 +/- 1.3 mg/kg. RESULTS: Midazolam requirement was significantly higher in patients with stem cell transplantation (0.09 +/- 0.05 mg/kg) compared with controls (0.06 +/- 0.03 mg/kg; p = 0.0002). In the HIV patients with drug abuse (0.12 +/- 0.10 mg/kg), there was a tendency for the need of a higher dose of midazolam compared with the control group (p = 0.0754). CONCLUSION: Stem cell transplant recipients and selected HIV patients with drug abuse need higher doses of midazolam for bronchoscopy.

Bronchoalveolar Lavage↗
PubMed1997

Long-term treatment of a breastfeeding mother with fluconazole-resolved nipple pain caused by yeast: a case study.

This case follows a breastfeeding mother with cracked nipples undergoing antibiotic treatment (dicloxacillin) for mastitis. Nipple candidiasis also presented with burning, stinging pain radiating from the nipples into the breast, lasting throughout feedings and beyond. Over a 7-week period, the asymptomatic infant was treated with the oral antifungal, nystatin. After other antifungal treatment regimens (oral nystatin, tristatin ointment) had been deemed unsuccessful for the mother, the physician prescribed fluconazole (200 mg loading dose plus 100 mg/day for 15 days) which reduced, but did not eliminate, the nipple yeast and accompanying pain. Fluconazole was continued for an additional 30 days (200 mg/day) for a total of 6 weeks of treatment with this medication. Concurrently, a topical yeast medication (tristatin ointment) was used for a total of 8 weeks on the nipples/areola, after which the overt pain was resolved. Although the mastitis resolved after 1 week, the cracked nipples did not completely heal for several months. During the initial 3 weeks of treatment, neither over-the-counter pain medication nor acetaminophen with codeine relieved this mother's pain. Hydrocodone bitartrate and acetaminophen (10/650 mg/tablet) (Lorcet) offered the pain relief necessary for this mother to continue to breastfeed.

Antifungal Agents↗
PubMed1996

Popliteal sciatic nerve block for postoperative analgesia.

Eighty-six patients were evaluated prospectively following the placement of a sciatic nerve block in the popliteal fossa after a major foot or ankle operation. Needle placement was guided by a peripheral nerve stimulator and 30 ml of 0.5% bupivacaine with epinephrine was used. Ninety-seven percent of patients had a successful block. Only one patient had severe discomfort during the block placement. The block lasted an average of 20 hours. During the first 24 hours after surgery, patients took an average of three hydrocodone tablets. Twenty-two of the 23 patients who had had previous major foot or ankle surgery found that the block was better than their previous pain control regimen. No patient had complications related to the block and 95% were satisfied and would have the block again.

Adolescent↗
PubMed2004

Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor.

UNLABELLED: In this multicenter, double-blinded, randomized, placebo-controlled study we evaluated the analgesic and opioid-sparing efficacy of a preoperative dose of i.v. parecoxib followed by oral valdecoxib in treating pain associated with elective laparoscopic cholecystectomy. Patients were randomized to receive a single i.v. dose of parecoxib 40 mg (n = 134) or placebo (n = 129) 30-45 min before induction of anesthesia. Six to 12 h after the i.v. dose, the parecoxib group received a single oral dose of valdecoxib 40 mg, followed by valdecoxib 40 mg qd on postoperative days 1-4, then 40 mg qd prn days 5-7. The placebo i.v. group received oral placebo on an identical schedule. All patients were allowed supplemental i.v. fentanyl as needed during the first 4 h postoperatively (T0-240 min) followed by hydrocodone 5 mg/acetaminophen 500 mg (Vicodin(R); 1-2 tablets orally every 4-6 h as needed). Patients taking parecoxib used 21% less fentanyl than those receiving placebo (P = 0.011). The mean area under the curve of pain intensity (PI) scores over time from T0-240 min was 55.2 for parecoxib and 61.2 for placebo (P = 0.083). At T180 and T240 min, mean PI score was 7.0 and 7.6 points lower in the parecoxib group, respectively (P < 0.02). Fewer patients on valdecoxib required supplemental analgesics (P < 0.05) after discharge. At T240 min and at day 7, Patient's and Physician's/Nurse's Global Evaluations were significantly better in the parecoxib/valdecoxib group (P < 0.05). Incidences of adverse events, adverse events causing withdrawal, and serious adverse events were less for parecoxib/valdecoxib than for placebo. The authors conclude that preoperative parecoxib is a valuable opioid-sparing adjunct to the standard of care for treating pain after laparoscopic cholecystectomy, and subsequent treatment with oral valdecoxib extends this clinical benefit. IMPLICATIONS: Parecoxib 40 mg i.v., 30-45 min preoperatively followed by oral valdecoxib 40 mg qd reduced opioid requirements and provided superior pain relief as well as improved patient global evaluation after laparoscopic cholecystectomy.

Administration, Oral↗
PubMed2005

Usage of pain medications during stroke rehabilitation: the Post-Stroke Rehabilitation Outcomes Project (PSROP).

Pain remains one of the most common, yet most challenging, medical problems in health care today, and it is one of the most common complications that occurs after a stroke. Pain can affect the course of stroke rehabilitation adversely, and it occasionally may be a cause for transfer back to an acute care hospital. The Post-Stroke Rehabilitation Outcomes Project (PSROP) database was used to describe the incidence of pain by body location and trends in the use of different classifications of medications to treat pain. Of the 1,122 participants in the PSROP database, the most common locations of pain in stroke survivors were the head, leg, back, and shoulder. The most frequently prescribed classifications of pain medications were other analgesics (acetaminophen and tramadol), followed by narcotic analgesics, non-steroidal antiinflammatory drugs (NSAIDs), anticonvulsants, and tricyclic antidepressants. After acetaminophen, the most frequently prescribed medications in each classification, respectively, include hydrocodone APAP, cox-2 inhibitors, gabapentin, and amitriptyline. Other frequently prescribed pain medications included sumatriptan (migraine analgesic), cyclobenzaprine (muscle relaxant), and baclofen (antispasticity muscle relaxant). Medications should be chosen based upon the medical condition causing pain, the ability of the stroke survivor to comply with administration of the medication, and the cost of the medication. Appropriate and timely treatments of painful conditions result in maximum function and the ability to lead active lives and maintain an adequate quality of life.

Aged↗
PubMed2005

A 46-year-old man with excruciating shoulder pain.

A 46-year-old man with no significant medical history presented to his local emergency department complaining of excruciating right shoulder pain. The patient was in his usual state of excellent health until 4 days prior, when right shoulder pain developed while he was using a chainsaw to cut wood. The next day, flu-like symptoms developed with fevers, chills, and headache. An MRI revealed that the right pectoralis major was torn from its attachment to the acromion. His shoulder pain intensified despite treatment with hydrocodone and acetaminophen, and the flu-like symptoms progressed over the next 2 days. Finally, on the day of hospital admission, he was weak and unable to arise out of bed. He was taken by family members to the local emergency department.

Abdominal Wall↗
PubMed2004

Carisoprodol withdrawal syndrome.

A 43-year-old man with chronic back and shoulder pain was treated with hydrocodone. He began taking excessive amounts of the drug, so his physicians stopped prescribing it. The patient then obtained the muscle relaxant carisoprodol on his own from several sources. He was consuming up to 30 or more tablets/day (> or =10,500 mg/day) for several weeks, then abruptly stopped taking the drug. Within 48 hours he developed anxiety, tremors, muscle twitching, insomnia, auditory and visual hallucinations, and bizarre behavior. The symptoms intensified and peaked on the fourth day after carisoprodol cessation. The patient required brief treatment with olanzapine and tapering dosages of lorazepam while the symptoms gradually resolved. To our knowledge, this is the first documented case of a withdrawal syndrome with carisoprodol. The symptoms most likely resulted because of accumulation of meprobamate, the active metabolite of carisoprodol in humans. Clinicians prescribing carisoprodol should be aware of the possibility for abuse or addiction. Further, we recommend that carisoprodol be designated a controlled substance at the federal level.

Adult↗
PubMed2004

Fracture of an endoluminal nitinol stent used in the treatment of tracheal collapse in a dog.

A 5-year-old castrated male Pomeranian was evaluated because of severe dyspnea and coughing, and a diagnosis of complete, static collapse of the trachea at the thoracic inlet was made. After failure to improve with medical management alone, an endoluminal tracheal stent was placed, which resulted in resolution of signs. Ten weeks after stent placement, the dog underwent tracheal resection and anastomosis because the stent had fractured at the level of the thoracic inlet. One year after surgery, the dog was doing well and required treatment with hydrocodone infrequently. Compared with other surgical treatment options, placement of an endoluminal tracheal stent is a relatively noninvasive intervention that can provide effective relief from the clinical signs associated with tracheal collapse in dogs. Implantation of endoluminal tracheal stents may be associated with complications; therefore, the procedure may best be regarded as a salvage procedure for dogs with end-stage disease that are refractory to appropriate medical management, have extensive collapse of the intrathoracic portion of the trachea, or are poor candidates for surgery.

Alloys↗
PubMed2000

Mechanistic studies of morphine dehydrogenase and stabilization against covalent inactivation.

Morphine dehydrogenase (MDH) of Pseudomonas putida M10 catalyses the NADP(+)-dependent oxidation of morphine and codeine to morphinone and codeinone. This enzyme forms the basis of a sensitive detection and assay method for heroin metabolites and a biotransformation process for production of hydromorphone and hydrocodone. To improve these processes we have undertaken a thorough examination of the kinetic mechanism of MDH. Sequence comparisons indicated that MDH belongs within the aldose reductase enzyme family. MDH was shown to be specific for the pro-R hydrogen of NADPH. In steady-state kinetic studies, product inhibition patterns suggested that MDH follows a Theorell-Chance mechanism for codeinone reduction at pH 7, and a non-Theorell-Chance sequential ordered mechanism for codeine oxidation at pH 9.5. Residues corresponding to the catalytically important Tyr-48, Lys-77 and Asp-43 of aldose reductase were modified by site-directed mutagenesis, resulting in substantial loss of activity consistent with a catalytic role for these residues. Loss of activity of MDH in the presence of the reaction product morphinone was found to be due to the formation of a covalent adduct with Cys-80; alteration of Cys-80 to serine resulted in an enzyme with greatly enhanced stability.

Alcohol Oxidoreductases↗
PubMed2000

Modification of screening immunoassays to detect sub-threshold concentrations of cocaine, cannabinoids, and opiates in urine: use for detecting maternal and neonatal drug exposures.

Testing for drugs of abuse in urine is commonplace in emergency departments and neonatal units. However, the clinical sensitivity of immunochemical screening methods is limited by the threshold concentrations used to distinguish between positive and negative specimens. Immunochemical screening methods for cocaine metabolite (benzoylecgonine), cannabinoids, and opiates in urine were recalibrated to detect drugs at lower threshold concentrations. The precision and linearity of the signals at the modified thresholds were verified by diluting drug-positive urine specimens to concentrations below the conventional cutoff concentration and measuring the rate signals in triplicate. To assess the clinical performance of the modified methods, specimens that tested negative using the unmodified assays were re-screened at the lower threshold, and specimens that re-screened positive were submitted for gas chromatographic/mass spectrometric (GC/MS) confirmation. Reproducibility of sub-threshold measurements was comparable to the unmodified assays, and rate separations between successive dilutions were sufficient to give semi-quantitative results. Using the lower thresholds, drugs were detected in 4-5% of the subjects that had screened negative at the conventional threshold concentration. GC/MS analysis confirmed the presence of cannabinoids and cocaine metabolite in 74% and 84%, respectively, of urine specimens that re-screened positive. Morphine, codeine, hydromorphone, or hydrocodone was detected by GC/MS analysis in 31% of opiate-positive re-screens.

Adult↗
PubMedDate not supplied

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Aciclovir, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate, antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine; Bacillus Calmette-Guérin, basiliximab, bicalutamide, bimatoprost, BMS-214662, brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine, carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin, dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720, fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine, glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a, interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost, levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride, methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330; Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride; Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab, rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate; Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir hydrochloride, visilizumab; Zidovudine.

Drug Therapy↗