Doses Of Hydrocodone Research Articles

Falls in Skilled Nursing Facilities Associated with Opioid Use

Intrigued by the study by Buckeridge and colleagues,1 we examined fall and opioid use data in 352 long-term care skilled nursing beds in three Eddy Foundation facilities in the Capital Region of New York State. We excluded a subacute care unit where patients commonly receive pain medication for postoperative pain. We extracted falling data for the second quarter of 2011. Of 222 falls, 126 (56.7%) occurred in facility residents who were using opioids, whereas only 27.5% of residents were receiving opioids (likelihood of falling 0.140 per patient per month for those receiving any opioid prescription vs 0.041 for those not receiving any opioid, relative risk = 3.45, 95% confidence interval = 2.74–4.34). Of the 126 falls, 23 (18.3%) were associated with use of a short-acting opioid within the prior 4 hours (five tramadol, 17 hydrocodone, one oxycodone). Only one (0.8%) was associated with use of a long-acting opioid within the prior 6 hours (MS-Contin, with a recent doubling of dosage in this individual). The finding in the Buckeridge study, that fall risk was more associated with the introduction of a new or increased hydrocodone dose than with more-potent opioids, seems counterintuitive. Nevertheless, our limited data are consistent with this finding, suggesting an explanation; as an “entry” drug, hydrocodone is commonly given to patients who are opioid-naive. This may result in greater susceptibility to the opioid's effects on level of consciousness or stability of gait, particularly with rapid onset of effect. We are now designing an interventional study to monitor fall rates as we further encourage reduced use of short-acting opioids and reduced use of as-needed orders. The available evidence appears to support such interventions. Conflict of Interest: There were no conflicts of interest for any of the authors. Author Contributions: M Wolff: concept, data analysis, and writing. R Kewley: concept, data extraction, and analysis. MC Hassett: data extraction and analysis. J Collins: concept, data analysis, and review. M Brodeur: concept and data review. S Nokes: data extraction. Sponsor's Role: There was no direct sponsorship of this study.

Acetaminophen modulation of hydrocodone reward in rats

Abuse of prescription opioid analgesics in non-medical context has been on the rise over the past decade. The most commonly abused analgesic in this drug class consists of a combined formulation of hydrocodone and acetaminophen. The present study was aimed to determine the rewarding effects of hydrocodone, acetaminophen, and their combination using the conditioned place preference (CPP) paradigm. Using a 6-day CPP paradigm, rats were paired with hydrocodone (0.5, 1.0 or 5.0mg/kg) or acetaminophen (50, 100 or 300mg/kg) to determine whether the drugs given alone would produce a CPP. Rats conditioned with the highest dose of hydrocodone exhibited place preference, whereas rats conditioned with acetaminophen did not demonstrate place preference. In a second experiment, varying doses of hydrocodone and acetaminophen were combined to determine whether acetaminophen would enhance hydrocodone reward. Acetaminophen (100mg/kg) enhanced the rewarding effects of hydrocodone (1mg/kg), although the effect was unique to this particular dose combination. Higher or lower doses of acetaminophen combined with hydrocodone did not alter hydrocodone CPP. The present findings suggest that acetaminophen has a limited potential of modulating the rewarding properties of hydrocodone in rats.

Use of an algorithm applied to urine drug screening to assess adherence to a hydrocodone regimen

This study examined the ability of an algorithm applied to urine drug levels of hydrocodone in healthy adult volunteers to differentiate among low, medium and high doses of hydrocodone. Twenty healthy volunteers received 20, 60 and 120 mg daily doses of hydrocodone dosed to steady-state at each level while under a naltrexone blockade. Using a florescence polarization immunoassay (FPIA), two urine samples were taken at each dosing level from each participant once steady-state was reached. The concordance was calculated for raw and adjusted FPIA urine hydrocodone values within each study participant across all doses. An analysis of medians was calculated for each of the dosage groupings using Bonett-Price confidence intervals for both raw and adjusted FPIA values. Finally, the Somers' D rank order analysis was performed for both raw and adjusted FPIA methods followed by a linear comparison of parameters to further determine which lab value reporting method produced a better fit with dosage. The concordance correlation coefficient for the pairs of raw urine FPIA values was 0·339, while the concordance correlation coefficient for the pairs of normalized FPIA values using the algorithm was 0·677. While some overlap of the confidence intervals was observed using the raw FPIA values, the intervals for the adjusted FPIA levels did not overlap between any dose levels, despite the application of a Bonferroni adjustment to correct for multiple comparisons. Results of the Somers' D analyses suggest that the adjusted FPIA method is 15% more likely to be concordant with dose than the raw value method. In contrast to raw FPIA values, an algorithm that normalizes hydrocodone urine drug levels for PH, specific gravity and lean body mass discriminates well between all three of the daily doses of hydrocodone tested (20, 60 and 120 mg), even when correcting for multiple analyses.

Fatal Hydrocodone Overdose in a Child: Pharmacogenetics and Drug Interactions

Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection. The concentration of hydrocodone in postmortem blood was in the range associated with fatality; however, hydromorphone, a major metabolite catalyzed by cytochrome P450 2D6 (CYP2D6), was not detected when using mass spectrometry. Genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway (CYP2D6*2A/*41). Coadministration of clarithromycin (a potent cytochrome P450 3A4 inhibitor) for an ear infection and valproic acid for seizures since birth further prevented drug elimination from the body. This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child.

Maximum daily dose of hydrocodone

Opioid analgesics are a well-established treatment for acute and chronic cancer-related pain, end-of-life care, and chronic noncancer-related pain.[1][1] Because of intrapatient variability in physical dependence, opioid tolerance, subjectivity of pain, and biopsychosocial influences, exact opioid

Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: Evidence from two parallel in vitro mouse models

Objective Acetaminophen/hydrocodone, a commonly used analgesic preparation, has been linked to rapidly progressing sensorineural hearing loss in human patients. The cellular and molecular mechanisms underlying the ototoxic effects of this drug combination are currently unknown, but are usually associated with high doses of hydrocodone. This study was aimed at identifying the specific agent responsible for hearing loss from toxic killing of cochlear sensory cells. Study Design Dose-response study. Setting University laboratory and private research facility. Subjects and Methods Math1 green fluorescent protein neonatal mouse cochlear cultures as well as a mouse auditory cell line (HEI-OC1) were exposed in vitro to different concentrations of acetaminophen, hydromorphone (the active metabolite of hydrocodone), and the micronutrient L-carnitine, either alone or combined. Using fluorescent and light microscopy, we quantified the sensory hair cells from a 600-μm basal segment before and after treatment. Acetaminophen/hydrocodone-induced apoptosis of HEI-OC1 was evaluated by caspase 3-activation studies. Statistically significant cell survival was determined with Student t test and analysis of variance. Results Cell death was associated mainly with exposure to acetaminophen, was slightly potentiated when combined with hydromorphone, and was partially prevented by L-carnitine. Exposure to hydrocodone or hydromorphone alone failed to kill either cochlear hair cells or HEI-OC1 cells. Conclusion Our findings point to acetaminophen, rather than hydrocodone, as the primary cytotoxic agent. Hydrocodone, however, may work synergistically with acetaminophen, increasing the damage to auditory cells. These findings are an important first step toward understanding the mechanism of acetaminophen/hydrocodone ototoxicity and may lead to future treatment strategies for hearing loss from ototoxic medications.

6β-naltrexol preferentially antagonizes opioid effects on gastrointestinal transit compared to antinociception in mice

Aims The current studies were designed to compare the in vivo potencies of the opioid antagonists 6β-naltrexol and naltrexone in blocking the effects of the opioid agonist hydrocodone following intravenous (i.v.) or oral (p.o.) administration. Main methods Adult male CD-1 mice were used for all experiments. The 55 °C tail-flick assay was used to assess the CNS antinociceptive activity of hydrocodone, and a charcoal meal gastrointestinal transit assay was used to assess the peripheral effects of hydrocodone. Graded antagonist dose–response curves for i.v. and p.o. 6β-naltrexol and naltrexone were generated to determine ID 50 antagonist potency estimates against fixed doses of hydrocodone. Key findings Both antagonists produced dose-related blockade of hydrocodone-induced antinociception and inhibition of gastrointestinal transit. Naltrexone was between 5- and 13-fold more potent than 6β-naltrexol in blocking a CNS effect of hydrocodone, whereas the drugs were nearly equipotent in blocking inhibition of gastrointestinal transit. Co-administration studies indicated an approximate 10-fold greater potency of 6β-naltrexol for antagonism of hydrocodone-induced inhibition of gastrointestinal transit versus antinociception, whereas naltrexone blocked both effects with near equal potency. 6β-naltrexol produced a longer duration of antagonist blockade and had a slower time to peak effect compared to naltrexone. Significance The pharmacology of 6β-naltrexol differentiates it from currently available opioid antagonists. This includes an intermediate selectivity for peripheral versus central opioid receptors, a long duration of action, and neutral antagonist qualities in opioid exposed systems. These properties render it a drug candidate for a co-formulation product with opioid analgesics to reduce peripheral opioid side effects and limit abuse potential.

Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers

Background Non-medical use and abuse of prescription opioids is a significant problem in the United States. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. The purpose of this study was to directly compare the psychopharmacological profile of two widely prescribed and abused oral opioid combination products within the same subject. Methods Twenty non-drug-abusing volunteers participated in a crossover, randomized, double-blind study in which they received, all p.o.: placebo; 975 mg acetaminophen (ACET); 10 mg oxycodone (OXY)/487 mg ACET; 20 mg OXY/975 mg ACET; 15 mg hydrocodone (HYD)/487 mg ACET; and 30 mg HYD/975 mg ACET. OXY and HYD doses were chosen to equate the drugs on an objective measure of opiate effects: miosis. Dependent measures were subjective, psychomotor/cognitive, reinforcing, and physiological effects, and relative potency estimates. Results In general, the two opioid combination products at equi-miotic doses produced similar prototypic opiate-like effects and psychomotor impairment, and of similar magnitude. The higher dose of OXY/ACET produced slightly more abuse liability-related subjective effects than the higher dose of HYD/OXY, but also produced slightly more negative effects. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated that OXY/ACET was approximately 1.5 times more potent than HYD/ACET. Conclusions Consistent with a recent study published in this journal using identical doses of HYD and OXY (without ACET) in prescription opioid abusers (Walsh, S.L., Nuzzo, P.A., Lofwall, M.R., Holtman Jr., J.R., 2008. The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription drug abusers. Drug Alcohol Depend. 198, 191–202), we found little difference in the pharmacodynamic effects of HYD/ACET and OXY/ACET in non-drug-abusing volunteers.

Open versus Minimally Invasive Lumbar Microdiscectomy: Comparison of Operative Times, Length of Hospital Stay, Narcotic Use and Complications

To determine if a minimally invasive approach to lumbar microdiscectomy reduces post-operative pain, length of hospital stay, or frequency of complications we retrospectively compared medical records of single level microdiscectomy patients by a single surgeon performed using a traditional open approach versus a minimally invasive approach. Thirty-five patients were in the open group: 63% male, average age 41.2 years, and 31 patients were in the minimally invasive group: 68% male, average age 42.1 years. There was no difference in surgical time or blood loss between the open and minimally invasive groups: 84.1 versus 76.8 minutes and 51.4 versus 69.7 mL, respectively. There were no significant complications intraoperatively or within the 30 day post-op period for either group. The average dose of intravenous morphine taken was 12.9 mg for the minimally invasive group and 15.7 mg for the open group (P=0.04). The average dose of hydrocodone was 13.4 mg for the minimally invasive group and 20.9 mg for the open group (P=0.03). The open group took an average of 11.7 mg oxycodone, the minimally invasive none. 45.2% of patients in the minimally invasive group were discharged on the same day as surgery compared to 5.75% in the open group (P=0.001). Microdiscectomy was performed safely and effectively through a minimally invasive expanding retractor system and operating microscope. Surgical times, blood loss, complications, and outcome were similar to a traditional open microdiscectomy while pain medication requirements and hospitalization were significantly less.

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.

Do gender and race affect decisions about pain management?

To determine if patient gender and race affect decisions about pain management. 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. 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). 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.

Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain

ObjectiveThe objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. BackgroundHydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics. MethodsThis randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours. ResultsMean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 Accepted for publication June 7, 2000. Printed in the USA. Reproduction in whole or part is not permitted. 990 0149-2918/00/$19.00 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 [1.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects. ConclusionsThis study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain

The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.