[Quantitative determination of conditions of extraction of hydrocodone from aqueous solutions by organic solvents depending on the pH of the medium].
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Codeine↗
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[Photoelectric colorimetric determination of hydrocodon phosphate in drug mixtures].
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Colorimetry↗
[Use of hydrocodon phosphate tablets with expectorants in the treatment of pulmonary tuberculosis].
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Adult↗
Profound hearing loss associated with hydrocodone/acetaminophen abuse.
OBJECTIVES: To describe profound hearing loss associated with hydrocodone overuse and the successful rehabilitation of these patients with cochlear implantation. STUDY DESIGN: Retrospective review. SETTING: A tertiary otologic referral center. PATIENTS: Twelve patients with rapidly progressive hearing loss and a concurrent history of hydrocodone overuse. INTERVENTIONS: Comprehensive medical histories, physical findings, audiometric tests, and, in those patients undergoing cochlear implantation, postimplantation performance data were reviewed. MAIN OUTCOME MEASURES: Clinical characteristics of hydrocodone-related hearing loss and open set word and sentence performance in those patients undergoing cochlear implantation. RESULTS: Hydrocodone overuse was associated with rapidly progressive sensorineural hearing loss in 12 patients. In four patients the initial presentation was unilateral, and two of the patients experienced vestibular symptoms. None of the 12 patients experienced improved thresholds after high-dose prednisone. Seven of the eight patients undergoing cochlear implantation have demonstrated early success with their devices. CONCLUSIONS: Hydrocodone is frequently prescribed in combination with acetaminophen for the relief of pain and has a side effects profile similar to other medications in its class. Although not described previously, overuse or abuse can be associated with a rapidly progressive sensorineural hearing loss. These patients can be successfully rehabilitated with cochlear implantation.
Acetaminophen↗
Evaluation of two opioid-acetaminophen combinations and placebo in postoperative oral surgery pain.
STUDY OBJECTIVE: To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery. DESIGN: Randomized, double-blind, single-dose, placebo-controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6. SETTING: Private, oral surgery practice sites. PATIENTS: Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data. INTERVENTIONS: Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports. MEASUREMENTS AND MAIN RESULTS: This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment. CONCLUSIONS: A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.
Acetaminophen↗
[Heroin addicts in substitution programs].
40 heroin addicts of whom 20 were undergoing maintenance therapy with hydrocodone (Dicodid) and another 20 with methadone have been questioned by standardized interview regarding their previous history and present situation. With data on the history we examined how well heroin addicts succeed in getting away from criminality and prostitution and look for employment while undergoing drug maintenance therapy. We were also interested to learn whether reaching the aim depended on the maintenance medication, i.e. if hydrocodone is as appropriate as methadone for maintenance therapy. The inquiry showed a significant reduction of criminality and prostitution. The rate of employment was quite stable. The therapeutic successes, measured by employment, prostitution and criminality did not differ with medication by hydrocodone or methadone. Although the more reliable patients received hydrocodone and the less reliable methadone, they did not differ either in past history or in therapeutic success. We conclude that hydrocodone can be recommended for maintenance therapy of relatively reliable heroin addicts.
Adult↗
Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004.
UNLABELLED: OxyContin (Purdue Pharma L.P., Stamford, Conn) was approved by the Food and Drug Administration (FDA) in 1995 as a sustained-release preparation of oxycodone hydrochloride and was thought to have much lower abuse potential than immediate-release oxycodone because of its slow-release properties. However, beginning in 2000, widespread reports of OxyContin abuse surfaced. In response, Purdue Pharma L.P. sponsored the development of a proactive abuse surveillance program, named the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system. In this paper, we describe results obtained from one aspect of RADARS--the use of drug abuse experts (ie, key informants)--as a source of data on the prevalence and magnitude of abuse of prescription drugs. The results indicate that prescription drug abuse has become prevalent, with cases reported in 60% of the zip codes surveyed. The prevalence of abuse was rank ordered as follows: OxyContin >or= hydrocodone > other oxycodone > methadone > morphine > hydromorphone > fentanyl > buprenorphine. In terms of the magnitude of abuse (>or=5 cases/100,000 persons in a 3-digit zip code), modest growth was seen with all analgesics over the 10 calendar quarters we monitored, but was most pronounced with OxyContin and hydrocodone. These results indicate that OxyContin abuse is a pervasive problem in this country, but that it needs to be considered in the context of a general pattern of increasing prescription drug abuse. PERSPECTIVE: Over the past 5 years, there have been reports, frequently anecdotal, that opioid analgesic abuse has evolved into a national epidemic. In this study, we report systematic data to indicate that opioid analgesic abuse has in fact increased among street and recreational drug users, with OxyContin and hydrocodone products the most frequently abused. Steps need to be taken to reduce prescription drug abuse, but very great care needs to be exercised in the nature of these actions so the legitimate and appropriate use of these drugs in the treatment of pain is not compromised as a result.
Adolescent↗
Do gender and race affect decisions about pain management?
OBJECTIVE: To determine if patient gender and race affect decisions about pain management. DESIGN, SETTING, AND PARTICIPANTS: Experimental design using medical vignettes to evaluate treatment decisions. A convenience sample of 111 primary care physicians (61 men, 50 women) in the Northeast was asked to treat 3 hypothetical patients with pain (kidney stone, back pain) or a control condition (sinusitis). Symptom presentation and severity were held constant, but patient gender and race were varied. MEASUREMENTS AND MAIN RESULTS: The maximum permitted doses of narcotic analgesics (hydrocodone) prescribed at initial and return visits were calculated by multiplying mg per pill x number of pills per day x number of days x number of refills. No overall differences with respect to patient gender or race were found in decisions to treat or in the maximum permitted doses. However, for renal colic, male physicians prescribed higher doses of hydrocodone to white patients versus black patients (426 mg vs 238 mg), while female physicians prescribed higher doses to blacks (335 mg vs 161 mg, F1,85 = 9.65, P =.003). This pattern was repeated for persistent kidney stone pain. For persistent back pain, male physicians prescribed higher doses of hydrocodone to males than to females (406 mg vs 201 mg), but female physicians prescribed higher doses to females (327 mg v. 163 mg, F1,28 = 5.50, P =.03). CONCLUSION: When treating pain, gender and racial differences were evident only when the role of physician gender was examined, suggesting that male and female physicians may react differently to gender and/or racial cues.
Adult↗
Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids.
The influence of replacing the phenolic hydroxyl by the methoxy group on opioid receptor binding, analgesic and antitussive action was investigated in the corresponding couples morphine-codeine, hydromorphone-hydrocodone and O-desmethyltramadol (L 235)-tramadol. Binding was studied on rat whole brain membranes (without cerebellum) with the radioligands dihydromorphine (mu-site), ethylketocyclazocine (k-site), D-Ala2-D-Leu5-enkephalin (delta-site) and naloxone (no selective binding). Analgesia (tail flick) and antitussive action (NH3-vapour induced cough) was investigated in rats and ED50 values 10 min after i.v. application were calculated to compare efficacy. All free hydroxyl compounds had higher opioid receptor affinities than the corresponding methoxy derivatives and were more active at the mu-site. The methoxy derivatives codeine and tramadol only had low affinities lacking selectivity towards mu-, kappa-, or delta-binding. Hydrocodone in contrast showed strong and mu-selective binding. The hydroxy compounds had higher analgesic activity than the methoxy congeners and analgesia appeared to correlate with mu-binding affinity. Codeine and hydrocodone were weaker antitussives than the corresponding hydroxy compounds, whereas no significant difference was found between O-desmethyltramadol and tramadol. Only in the tramadol group the methoxy substitution increased antitussive potency in relation to analgesic potency.
Animals↗
Determination of 6-oxo-morphinans, as the oximes, by difference circular dichroism spectroscopy.
A negative Cotton effect is observed in the circular dichroism (CD) spectra of 6-oxo-morphinans in the wavelength range of n-pi* electron transitions. 6-oxo-Morphinans can be transformed into oxime derivatives with hydroxylamine and after oxime formation the CD spectra are significantly different. Oxime formation was monitored by CD and by HPLC. It was established that under the experimental conditions used oxime formation was complete within 90 min. The method suggested for the determination of 6-oxo-morphinans is based on the considerable differences between the ellipticities before and after the oxime formation. The ellipticity difference varies linearly with concentration in the range 2 x 10(-5)-5 x 10(-4) mol L(-1) for the three 6-oxo-morphinans examined (oxycodone, hydrocodone, and 14-hydroxycodeinone). For hydrocodone the dependence is also linear in a lower concentration range (5 x 10(-6)-10(-4) mol L(-1)). The new difference CD spectroscopic method can be applied to the selective determination of 6-oxo-morphinans in bulk and dosage forms.
Circular Dichroism↗
Patient-controlled ropivacaine analgesia after arthroscopic subacromial decompression.
PURPOSE: To evaluate the efficacy of a subacromial patient-controlled analgesia (PCA) infusion of 0.2% ropivacaine versus saline for postoperative pain control following arthroscopic shoulder surgery. TYPE OF STUDY: Double-blind prospective randomized study. METHODS: A prospective, randomized double-blind study was performed on a consecutive group of 24 patients. All patients had arthroscopic subacromial decompression. Ropivacaine was chosen as the study drug due to the association of cardiac toxicity with the use of bupivacaine. The surgeon, anesthesiologist, and the operating room staff were blinded to the randomization. Immediately before surgery, the pharmacy staff randomized the type of drug infusion. Patients were asked to record their pain score using a visual analog scale (VAS) along with the amount of hydrocodone consumption for the first 2 days after surgery. RESULTS: Nineteen patients completed the study. Ten patients received a subacromial infusion of 0.2% ropivacaine at 5 mL per hour with a bolus dose of 2 mL at a 15-minute lockout period via a microjet PCA pump (group I). Nine patients received saline in the same experimental conditions (group II). The use of a PCA ropivacaine infusion (group I) resulted in a significant reduction of postoperative pain by 34% as measured by VAS scale (P <.05), but no changes in the amount of hydrocodone consumption. CONCLUSIONS: The use of subacromial 0.2% ropivacaine PCA infusion provided effective postoperative pain control. LEVEL OF EVIDENCE: Level I.
Acetaminophen↗
The effect of FDA approval of a generic competitor to OxyContin (oxycodone HCl controlled-release) tablets on the abuse of oxycodone.
Controversy exists concerning whether abuse of oxycodone will increase after the introduction of generic controlled-release (CR) oxycodone. We evaluated the effect of FDA approval of generic CR oxycodone on the misuse/abuse of oxycodone, hydrocodone, methadone and morphine utilizing data from eight poison control centers (PCC). PCC intentional exposure (IE) reason codes were used as measures of abuse. Opioid-specific quarterly IE rates (per 100,000 population and per 10,000 patients) were calculated for 1 year before and after approval (March 24, 2004). Changes in regression slopes (1 year before to 1 year after) and in IE rates (1 quarter before to 1 quarter after) were analyzed using Poisson regression. The regression slopes for oxycodone, methadone and morphine did not change after approval but decreased significantly for hydrocodone. None of the prescription opioids' IE rates significantly increased after approval. When changes in oxycodone's IE rates were compared to the other opioids, no statistically significant differences were found, indicating a lack of time-opioid interaction. These results did not vary when population rates or patient rates were used. PCC data indicate that approval of generic CR oxycodone was not followed by an immediate unfavorable effect on the misuse/abuse of oxycodone.
Analgesics, Opioid↗
The influence of gender and race on physicians' pain management decisions.
This study set out to examine whether gender or race influences physicians' pain management decisions in a national sample of 712 (414 men, 272 women) practicing physicians. Medical vignettes were used to vary patient gender and race experimentally while holding symptom presentation constant. Treatment decisions were assessed by calculating maximum permitted doses of narcotic analgesic (hydrocodone) prescribed for initial pain treatment and for follow-up care. No overall differences by patient gender or race were found in decisions to treat or in maximum permitted doses. However, for persistent back pain, female physicians prescribed lower doses of hydrocodone, especially to male patients. For renal colic, lower doses were prescribed to black versus white patients when the patient was female, whereas the reverse was true when patients were male. These findings challenge a fairly extensive literature suggesting that physicians treat women and minorities less aggressively for their pain, and results offer further evidence that pain treatment decisions are influenced physician gender.
Adult↗
Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults.
BACKGROUND: Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting. OBJECTIVE: Two studies with identical protocols assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic surgery. METHODS: These were multicenter, randomized, placebo- and active-controlled, double-blind, parallel-group trials conducted between January and June 1998. Both consisted of a single-dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In the SDAP, patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour period. In the MDAP, extending from 8 hours after the first dose of study medication up to 5 days, patients who had received < or =1 dose of rescue medication during the SDAP continued on study medication (placebo recipients were rerandomized to active treatment), which could be taken up to 3 times a day as needed. RESULTS: A total of 418 patients were enrolled in the 2 trials. During the SDAP, 141 patients received celecoxib, 136 received hydrocodone/acetaminophen, and 141 received placebo. During the MDAP, 185 patients received celecoxib and 181 received hydrocodone/acetaminophen. When the combined data were analyzed, mean pain intensity difference (PID) scores generally favored the active treatments over placebo from 1 to 6 hours (with the exception of 1.5 hours) after dosing (P < or = 0.016) and favored celecoxib over the other treatments at 7 and 8 hours after dosing (P < 0.001). The active treatments demonstrated superior summed PID scores through 8 hours (P < 0.001), significantly shorter median times to onset of analgesia (P < 0.05), and significantly longer median times to first use of rescue medication (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain intensity scores (P < 0.001, days 2-5), required fewer doses of study medication (P < or = 0.01, days 3-5), and had superior scores on a modified American Pain Society Patient Outcome Questionnaire (P < or = 0.013). In addition, a significantly lower proportion of celecoxib-treated patients experienced adverse events (43%) compared with hydrocodone/acetaminophen-treated patients (89%; P < 0.001). CONCLUSIONS: Over 8 hours, patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain.
Acetaminophen↗
Zolpidem reduces postoperative pain, fatigue, and narcotic consumption following knee arthroscopy: a prospective randomized placebo-controlled double-blinded study.
Sixty-eight patients undergoing outpatient knee arthroscopy for treatment of meniscal tears or loose bodies were divided into three treatment groups (zolpidem [24 patients], control [24 patients], and placebo [20 patients]). All groups received postoperative hydrocodone and ibuprofen. Patients in the zolpidem group received a single dose of zolpidem tartrate for the first seven postoperative nights. Patients in the placebo group received a gelatin capsule similar in appearance to zolpidem and patients in the control group received only hydrocodone and ibuprofen. Patients in the control group demonstrated significantly worse mean daily postoperative pain and more daily postoperative fatigue on visual analog scales when compared with the zolpidem group (P=.03 and P=.04, respectively). Patients in the placebo group had worse daily postoperative pain and more daily postoperative fatigue when compared to the zolpidem group, although these differences did not reach statistical significance (P=.15, power=0.6; and P=.27, power=0.48, respectively). Patients in the control group consumed significantly higher quantities of hydrocodone/acetaminophen postoperatively (P=.04) than patients in the zolpidem group. Finally, patients in the placebo group consumed higher quantities of hydrocodone/acetaminophen than the zolpidem group although the difference did not reach statistical significance (P=.4; power=0.15). Power was calculated for each insignificant relationship based on observed effect and sample sizes and variances. This study demonstrates that sleep and fatigue may be an important factor in the effective pain management following knee arthroscopy. Future postoperative treatment regimens should address sleep and fatigue to maximize analgesic effects in these patients.
Acetaminophen↗
Patterns and trends in opioid use among individuals with back pain in the United States.
STUDY DESIGN: Secondary analysis of Medical Expenditure Panel Survey from 1996 to 1999. OBJECTIVE: To examine patterns in opioid use in 1996, 1997, 1998, and 1999 among individuals with back pain in the United States and to investigate trends in the use of overall and individual opioid category. SUMMARY OF BACKGROUND DATA: To the authors' best knowledge, no study has examined at a national level the patterns and trends in opioid use among individuals with back pain in the United States. METHODS: Individuals with back pain were stratified by sociodemographic characteristics and geographic regions. Rates of overall opioid use were compared among different strata by the use of simple and multivariate logistic regression models. To investigate trends in opioid use, use rates of the overall and individual opioid category in each year were calculated and compared. RESULTS: From 1996 to 1999, wide variations in overall opioid use were consistently observed among individuals with different educational levels, family income, and health insurance status. Regional variation in opioid use was also observed for most of the 4 years. After adjustment for covariates, health insurance status and geographic regions were consistent predictors of opioid use from 1997 to 1999. Trend analysis indicated that the rates of overall opioid use increased slightly across the 4-year span. Among individual opioid categories, the use of oxycodone or hydrocodone increased, whereas the use of propoxyphene decreased. CONCLUSIONS: The variation in overall opioid use among individuals with back pain with different sociodemographic characteristics and from different geographic regions suggested an opportunity to improve opioid prescribing patterns. The increase in the use of hydrocodone and oxycodone indicated a need to better assess the efficacy and safety associated with these drugs among individuals with back pain.
Adolescent↗
Biological synthesis of the analgesic hydromorphone, an intermediate in the metabolism of morphine, by Pseudomonas putida M10.
The morphine alkaloid hydromorphone (dihydromorphinone) was identified as an intermediary metabolite in the degradation of morphine by Pseudomonas putida M10. A constitutive NADH-dependent morphinone reductase capable of catalyzing the reduction of the 7,8-unsaturated bond of morphinone and codeinone, yielding hydromorphone and hydrocodone, respectively, was shown to be present in cell extracts. The structures have been identified by 1H nuclear magnetic resonance and mass spectrometry. Morphinone reductase has been partially purified by anion-exchange and gel filtration chromatography. This enzyme has potential applications as a biocatalyst for the synthesis of the highly potent analgesic hydromorphone and the antitussive hydrocodone.
Biodegradation, Environmental↗
[Determination of opiates in biological human samples by liquid chromatography-tandem mass spectrometry].
OBJECTIVE: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of opiates in biological samples according to the emerging problem in drugs abuse. METHODS: Opiates such as heroin, 6-acetylmorphine, morphine, codeine, acetylcodeine, hydrocodone and hydromorphone were isolated from human blood, urine, oral fluid and hair using a simple extraction and consequently analyzed using LC-MS/MS. The method was evaluated by real cases. RESULTS: The mobile phase give the optimum separation for opiates. The detection limit of morphine in urine with dilution and liquid-liquid extraction and in hair is 10ng/mL, 0.01 ng/mL and 0.01 ng/mg, respectively. CONCLUSION: The method is simple and rapid, offering superior sensitivity and selectivity for opiates. The target compounds comprising hydrocodone and hydromorphone enlarge the applied area.
Chromatography, Liquid↗