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1.
Medicina (Kaunas) ; 59(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36676742

RESUMO

Pharmacotherapy for major depressive disorder (MDD) typically consists of trial-and-error and clinician preference approaches, where patients often fail one or more antidepressants before finding an optimal regimen. Pharmacogenomics (PGx) can assist in prescribing appropriate antidepressants, thereby reducing the time to MDD remission and occurrence of adverse drug events. Since many antidepressants are metabolized by and/or inhibit cytochrome P450 enzymes (e.g., CYP2C19 or CYP2D6), drug-induced phenoconversion is common in patients on antidepressant combinations. This condition influences the interpretation of a patient's PGx results, overall risk of ineffective/adverse medication response due to multi-drug interactions, and the recommendations. This complex case describes a patient with MDD, generalized anxiety disorder, and chronic pain who experienced a fall due to excessive sedation following a prescribing cascade of fluoxetine, bupropion, and doxepin. These antidepressants delivered a significant additive sedative effect and interacted with the patient's hydrocodone, potentially contributing to uncontrolled pain, upward dose titration of hydrocodone, and a higher overall sedative burden. The PGx results and drug-induced phenoconversion described in this case report explain the patient's excessive sedation and possibly ineffective/toxic antidepressant and opioid treatment. This case report also illustrates how a more timely multi-drug interaction assessment (preferably in conjunction with preemptive PGx testing) may have informed a different prescribing pattern, reduced/avoided a prescribing cascade, and potentially prevented a drug-related fall.


Assuntos
Transtorno Depressivo Maior , Farmacogenética , Humanos , Farmacogenética/métodos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Hidrocodona/uso terapêutico , Antidepressivos/efeitos adversos , Fluoxetina/uso terapêutico
2.
Clin Biochem ; 112: 6-10, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36535386

RESUMO

BACKGROUND: Urine drug testing (UDT) monitors prescription compliance and/or drug abuse. However, interpretation of UDT results obtained by liquid chromatography-tandem mass spectrometry (LC-MS-MS) can be complicated by the presence of drug impurities that are detected by highly sensitive methods. Hydrocodone is a drug impurity that can be found as high as 1% in oxycodone pills. OBJECTIVES: We evaluated the frequency and concentration of hydrocodone and its metabolite, hydromorphone, in patients taking oxycodone to check if the ratio of hydrocodone or hydromorphone to oxycodone could distinguish between oxycodone only use from those consuming additional opiates. DESIGN & METHODS: We correlated LC-MS/MS results with medication records of 319 patients with positive oxycodone results over 7 months (4/2021-11/2021). RESULTS: Fifteen of 319 patients with positive oxycodone results were taking oxycodone only. For these 15 patients, the mean ratio of hydrocodone to oxycodone was 0.57% (range 0.05%-3.35%), and the mean ratio of hydromorphone to oxycodone was 0.81% (range 0.18-3.51%). CONCLUSIONS: Hydrocodone and/or hydromorphone are detectable in patients taking only oxycodone and can likely be identified as an impurity if their calculated ratio to oxycodone is <1 %. Further validation of the ratios in a larger sample size is recommended.


Assuntos
Hidrocodona , Transtornos Relacionados ao Uso de Opioides , Humanos , Hidrocodona/análise , Hidromorfona/análise , Oxicodona , Analgésicos Opioides , Cromatografia Líquida/métodos , Oximorfona , Espectrometria de Massas em Tandem/métodos
3.
J Public Health Dent ; 82(4): 491-494, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36210548

RESUMO

OBJECTIVE: To describe opioid prescribing trends among oral and maxillofacial surgeons (OMFS). METHODS: Prescriptions by OMFS were identified from IQVIA Longitudinal Prescription Dataset, 2016-2019. OMFS-based, patient-based and population-based prescribing rates and changes in high-risk opioid prescribing were calculated annually. We used linear regression to describe trends. RESULTS: There were 13.9 million opioid prescriptions among 12.5 million patients (627 prescriptions/OMFS/year). Hydrocodone and oxycodone decreased by 20.9% and 39.2% (p < 0.05), while tramadol and codeine increased by 24.3% and 6.1% (p < 0.05), respectively. Opioid prescribing rates significantly decreased by 27 prescriptions/OMFS/year, 18.6 patients/OMFS/year and by 0.9 prescriptions/100,000 population/year (p < 0.05 for all). From 2016 to 2019, the proportion of opioids >3 days decreased by 54.2% (p < 0.05) and prescriptions ≥50 MME/day decreased by 66.3% (p < 0.05). Although the number of opioid prescriptions by OMFS decreased in most states, 12% of states experienced increases. CONCLUSION: Opioid prescribing, especially high-risk prescribing, by OMFS has decreased. However, targeted interventions are warranted in some areas.


Assuntos
Analgésicos Opioides , Prescrições de Medicamentos , Humanos , Estados Unidos , Analgésicos Opioides/uso terapêutico , Cirurgiões Bucomaxilofaciais , Padrões de Prática Odontológica , Hidrocodona/uso terapêutico
4.
J Opioid Manag ; 18(5): 467-474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36226786

RESUMO

This study sought to determine if there were any changes in opioid prescribing habits of providers at a single institution after the implementation of legislation to increase opioid prescribing regulations. Our study demonstrated a 39.5 percent decrease in overall morphine milligram equivalent (MME) prescribed the year after the laws took effect when compared with the year prior. It is clear that these laws have been effective in decreasing the number of opioids prescribed at discharge from Mercy Health Grand Rapids. INTRODUCTION: Opioid use disorder has become an epidemic with approximately 130 people dying every day in the United States due to prescription and illegal opioid overdoses. In December 2017, the Michigan legislature ratified a package of 10 acts to address a variety of problems through several layers of regulations including more restrictive prescribing rules, which took effect in June 2018. OBJECTIVE: To evaluate the impact of legislation on the opioid prescribing habits of providers who discharged patients from a community-based academic teaching hospital. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was performed using data from a community-based academic teaching hospital with 303 beds, a medical ICU, labor and delivery unit, and a 42-room emergency department. All patients discharged from in-patient or observation status in the 12 months before and after June 1, 2018 were included. MAIN OUTCOMES AND MEASURES: The primary outcome was MMEs of opioids prescribed at discharge before (June 1, 2017 to May 31, 2018) and after (June 1, 2018 to May 31, 2019) legislation. Medications included morphine, hydrocodone, oxycodone, fentanyl, methadone, hydromorphone, tramadol, codeine, and meperidine. RESULTS: There were 17,227 patients discharged during the first 12-month period and 15,855 patients discharged in the second 12-month period. There were 14,064 new opioid prescriptions in total during these time periods. Total MME prescribed during the study period showed a 39.5 percent decrease from pre- (2,268,460 MME) to post-legislation (1,372,424 MME), while average MMEs/discharge significantly decreased (135.1 ± 321.2 vs. 87.6 ± 187.4; p < 0.001). Total pill/patch count decreased by almost 40 percent. For patients who were prescribed opioids, average MME/discharge showed significant decline after legislation implementation (309.6 ± 427.1 vs. 212.2 ± 242.1; p < 0.001). Average daily MME/patient prescribed an opioid remained similar between the time periods (52.4 ± 37.0 vs. 51.6 ± 35.0; p = 0.21). Significant reductions (p < 0.05) were seen in MMEs for each individual medication with the exception of acetaminophen-codeine and methadone. CONCLUSIONS AND RELEVANCE: Our results indicate that the legislation implemented in Michigan to regulate opioid prescriptions was associated with a reduction in opioids prescribed to patients discharged from a community-based academic teaching hospital.


Assuntos
Analgésicos Opioides , Tramadol , Acetaminofen/uso terapêutico , Analgésicos Opioides/efeitos adversos , Codeína/uso terapêutico , Endrin/análogos & derivados , Fentanila/uso terapêutico , Humanos , Hidrocodona/uso terapêutico , Hidromorfona/uso terapêutico , Meperidina/uso terapêutico , Metadona/uso terapêutico , Michigan , Oxicodona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Alta do Paciente , Padrões de Prática Médica , Estudos Retrospectivos , Tramadol/uso terapêutico , Estados Unidos
5.
Neuropharmacology ; 221: 109291, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36241086

RESUMO

Cytochrome P450 2D (CYP2D) metabolises many centrally-acting substrates including opioids. Hydrocodone, an opioid and CYP2D substrate, is metabolised to hydromorphone, an active metabolite. CYP2D in the brain is active in vivo and can alter drug response however, it is unknown whether metabolism by CYP2D in the brain alters oral hydrocodone induced analgesia. Propranolol, a selective CYP2D mechanism-based inhibitor, or vehicle, was administered into the right cerebral ventricle of male rats, (HAN Wistars, Envigo), 24 h before testing for analgesia from oral hydrocodone (or hydromorphone, a non-CYP2D substrate). Hydrocodone and its CYP2D-mediated metabolites were simultaneously quantified using a novel LC-MS/MS assay. After propranolol vs vehicle pretreatment, there was significantly higher analgesia from oral hydrocodone, and a significantly lower brain CYP2D metabolic ratio (an in vivo phenotype of brain CYP2D activity that was derived from the molar sum of hydromorphone and its metabolites divided by hydrocodone). The brain CYP2D metabolic ratio correlated significantly with analgesia. There was no pretreatment effect on plasma hydrocodone concentrations, elimination rates, or metabolic ratio (an in vivo phenotype for hepatic CYP2D activity). The liver CYP2D metabolic ratio did not correlate with analgesia. Propranolol pretreatment had no impact on analgesia from oral hydromorphone. These data suggest that inhibited CYP2D activity in brain, causing reduced metabolism of brain hydrocodone, resulted in higher analgesia from oral hydrocodone, despite hydrocodone having a lower µ-opioid receptor affinity than hydromorphone. Thus, variation in CYP2D in the brain may be an important source of interindividual differences in response to CYP2D substrates, including oral hydrocodone.


Assuntos
Analgesia , Hidrocodona , Animais , Masculino , Ratos , Hidrocodona/metabolismo , Hidrocodona/farmacologia , Hidromorfona/metabolismo , Hidromorfona/farmacologia , Cromatografia Líquida , Propranolol/farmacologia , Ratos Wistar , Espectrometria de Massas em Tandem , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/farmacologia , Dor/metabolismo , Analgésicos Opioides , Encéfalo
6.
J Opioid Manag ; 18(4): 327-334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052931

RESUMO

OBJECTIVE: In this study, we aim to look at opioid prescription patterns in a large pediatric hospital with an emphasis on opioid potency as measured by morphine milligram equivalents (MMEs) to understand physician response to safe prescribing regulations and new research on opioid use in pediatrics. DESIGN: Analgesic prescriptions in a pediatric hospital in California from 2012 to 2016 were included. Prescriptions that contained any type of opioid medication were analyzed total MME in each prescription, and medication prescribed. The MME for each opioid was assigned to the prescription and presented as mean ± standard deviation (SD). Statistical analysis was performed by using IBM SPSS statistics version 25. SETTING: A pediatric hospital in California. PARTICIPANTS: All pediatric patients receiving analgesic prescriptions from a single institution between 2012 and 2016. MAIN OUTCOME MEASURE: Relative frequency of different opioid medications -prescribed. RESULTS: Of the 14,194 total opioid prescriptions, hydrocodone (11,247), codeine (2,117), and tramadol (411) were most prescribed. The relative frequency of opioid prescription decreased from 2012 to 2016 due to the decreased prescription of hydrocodone and codeine. Despite the decreased relative frequency of opioid prescription, the mean MME of prescribed opioids increased. CONCLUSION: The study demonstrated that recent efforts to limit pediatric exposure to opioids have been effective. However, recommendations limiting the use of weak opioids (codeine and tramadol) have caused an increase in average prescribed opioid potency. This may be a contributing factor to the overall increase in opioid-related pediatric hospitalizations. Revision of prescription guidelines for hydrocodone (MME = 1) may protect pediatric patients from unnecessary opioid exposure.


Assuntos
Pediatria , Tramadol , Analgésicos Opioides/efeitos adversos , Criança , Codeína , Prescrições de Medicamentos , Hospitais Pediátricos , Humanos , Hidrocodona , Padrões de Prática Médica , Tramadol/efeitos adversos
7.
Sci Rep ; 12(1): 15569, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114250

RESUMO

Drug interactions involving benzodiazepines and related drugs (BZDs) are increasingly recognized as a contributor to increased risk of unintentional traumatic injury. Yet, it remains unknown to what extent drug interaction triads (3DIs) may amplify BZDs' inherent injury risk. We identified BZD 3DI signals associated with increased injury rates by conducting high-throughput pharmacoepidemiologic screening of 2000-2019 Optum's health insurance data. Using self-controlled case series design, we included patients aged ≥ 16 years with an injury while using a BZD + co-dispensed medication (i.e., base pair). During base pair-exposed observation time, we identified other co-dispensed medications as candidate interacting precipitants. Within each patient, we compared injury rates during time exposed to the drug triad versus to the base pair only using conditional Poisson regression, adjusting for time-varying covariates. We calculated rate ratios (RRs) with 95% confidence intervals (CIs) and accounted for multiple estimation via semi-Bayes shrinkage. Among the 65,123 BZD triads examined, 79 (0.1%) were associated with increased injury rates and considered 3DI signals. Adjusted RRs for signals ranged from 3.01 (95% CI = 1.53-5.94) for clonazepam + atorvastatin with cefuroxime to 1.42 (95% CI = 1.00-2.02, p = 0.049) for alprazolam + hydrocodone with tizanidine. These signals may help researchers prioritize future etiologic studies to investigate higher-order BZD interactions.


Assuntos
Lesões Acidentais , Benzodiazepinas , Alprazolam , Atorvastatina , Teorema de Bayes , Benzodiazepinas/efeitos adversos , Cefuroxima , Clonazepam , Interações Medicamentosas , Humanos , Hidrocodona
8.
Nursing ; 52(10): 56-61, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129510

RESUMO

PURPOSE: To determine the incidence of and predictors for serious opioid-related adverse drug events (ORADEs) in postoperative inpatients. METHODS: A retrospective cohort study design of serious ORADEs in surgical inpatients between 2015 and 2017, who were abstracted from the electronic health record, in an 800-bed academic medical health center. RESULTS: A total of 27,942 surgery patients met the inclusion criteria. Of those, 25,208 patients (90%) were exposed to opioids after surgery. A total of 25,133 (99.7%) patients exposed to opioids did not experience a serious ORADE while 75 (0.3%) patients did experience a serious ORADE and required naloxone. The predictors for ORADEs include age (OR = 1.040, P-value < .0001); gender (OR = 0.394, P-value = .0006); psychiatric disorder (OR = 4.440, CI: 2.435, 8.095); morphine level with respect to hydrocodone-acetaminophen (OR = 5.841, P-value = .0384); and were almost six times more likely to experience a serious ORADE when morphine is prescribed and 4.44 times more likely in patients with a psychiatric disorder (P-value < .0001). CONCLUSION: Once a baseline incidence is known, predictors for serious ORADEs in surgical inpatients are useful in guiding medical-surgical nurses' opioid safety practices, with more frequent focused respiratory assessments before opioid dosing and closer monitoring when opioids are prescribed postoperatively, especially in higher-risk surgical inpatients.


Assuntos
Analgésicos Opioides , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Acetaminofen , Analgésicos Opioides/efeitos adversos , Humanos , Hidrocodona , Incidência , Tempo de Internação , Naloxona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Estudos Retrospectivos
9.
Environ Toxicol Chem ; 41(11): 2658-2666, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35920352

RESUMO

Active pharmaceutical ingredient (API) contamination of water sources, including opioid contamination, has become more common in recent years. Although drinking water-treatment plants help mitigate API infiltration, API contamination remains in some drinking water sources. Therefore, the ability to detect APIs at ultratrace concentrations is vital to ensure safe drinking water. A method for the ultratrace determination of fentanyl, hydrocodone, and codeine in drinking water via direct injection and high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS) was developed and validated. Drinking water samples (10 ml) are simply syringe-filtered and then analyzed by HPLC-MS/MS. A wide linear range (0.25-100 ng/L) and ultratrace limits of detection (80, 150, and 500 pg/L for fentanyl, hydrocodone, and codeine, respectively) were features of the method. The method produced excellent aggregate accuracies of 90%-115% and precisions of ≤11% for the three analytes tested. This method was used to test drinking water samples from 53 US locations, with hydrocodone and codeine detected in approximately 40% of the samples tested at concentrations between 0.3 and 20 ng/L. Codeine was detected at higher concentrations than hydrocodone (up to 7.3 times) for each sample containing these APIs. Fentanyl was not detected in any field drinking water sample. The detection of opioids in a large fraction of the US drinking water samples tested is cause for concern, and these levels should continue to be monitored to ensure that they do not become a threat to human health. Environ Toxicol Chem 2022;41:2658-2666. © 2022 SETAC.


Assuntos
Água Potável , Humanos , Água Potável/química , Cromatografia Líquida de Alta Pressão , Analgésicos Opioides/análise , Espectrometria de Massas em Tandem/métodos , Hidrocodona/análise , Cromatografia Líquida/métodos , Prevalência , Codeína/análise , Preparações Farmacêuticas
10.
JAMA Netw Open ; 5(8): e2228588, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36001312

RESUMO

Importance: Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications. Objective: To compare the risk of NOWS across common types of opioids when prescribed as monotherapy during the last 3 months of pregnancy. Design, Setting, and Participants: This cohort study analyzed administrative claims data of Medicaid-insured mothers and newborns in 46 states and Washington DC from January 1, 2000, through December 31, 2014. Participants were mothers with 2 or more dispensed opioid prescriptions within 90 days before delivery and their eligible live-born neonates. Data were analyzed from February 2020 to March 2021. Exposure: Different types of opioid medications were compared by agonist strength (strong vs weak) and half-life (medium vs short and long vs short) of the opioid active ingredient. Main Outcomes and Measures: The primary outcome was NOWS, which was identified using an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code in the 30 days after delivery. Relative risks (RRs) were adjusted for an exposure propensity score, including demographic characteristics, comorbidities, other medication use, and opioid treatment characteristics (including morphine milligram equivalents), using fine stratification. Results: The cohort comprised 48 202 opioid-exposed pregnancies with live newborns. A total of 1069 neonates (2.2%) had NOWS and 559 (1.2%) had severe NOWS. Opioid exposure during pregnancy included 16 202 pregnancies exposed to codeine, 4540 to oxycodone, 1244 to tramadol, 260 to methadone (dispensed for pain), 90 to hydromorphone, and 63 to morphine compared with 25 710 exposed to hydrocodone. Demographic characteristics varied across opioids, with tramadol, oxycodone, methadone, hydromorphone, and morphine being more commonly dispensed at older maternal age (≥35 years). Compared with hydrocodone, codeine had a lower adjusted RR of NOWS (0.57; 95% CI, 0.46-0.70), with a similar adjusted RR for tramadol (RR, 1.06; 95% CI, 0.73-1.56), and 2- to 3-fold higher adjusted RRs for oxycodone (1.87; 95% CI, 1.66-2.11), morphine (2.84; 95% CI, 1.30-6.22), methadone (3.02; 95% CI, 2.45-3.73), and hydromorphone (2.03; 95% CI, 1.09-3.78). Strong agonists were associated with a higher risk of NOWS than weak agonists (RR, 1.97; 95% CI, 1.78-2.17), and long half-life opioids were associated with an increased risk compared with short half-life products (RR, 1.33; 95% CI, 1.12-1.56). Findings were consistent across sensitivity and subgroup analyses. Conclusions and Relevance: Results of this study show higher risk of NOWS and severe NOWS among neonates with in utero exposure to strong agonists and long half-life prescription opioids. Information on the opioid-specific risk of NOWS may help prescribers select opioids for pain management in late stages of pregnancy.


Assuntos
Doenças do Recém-Nascido , Síndrome de Abstinência Neonatal , Síndrome de Abstinência a Substâncias , Tramadol , Adulto , Analgésicos Opioides/efeitos adversos , Codeína , Estudos de Coortes , Feminino , Humanos , Hidrocodona , Hidromorfona , Recém-Nascido , Doenças do Recém-Nascido/induzido quimicamente , Metadona/uso terapêutico , Morfina , Síndrome de Abstinência Neonatal/tratamento farmacológico , Síndrome de Abstinência Neonatal/epidemiologia , Síndrome de Abstinência Neonatal/etiologia , Oxicodona/efeitos adversos , Dor/tratamento farmacológico , Gravidez , Prescrições , Síndrome de Abstinência a Substâncias/complicações , Estados Unidos/epidemiologia
11.
Curr Med Res Opin ; 38(11): 1947-1957, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36000252

RESUMO

OBJECTIVE: This study sought to: (1) construct and validate a composite potential opioid misuse score; and (2) compare potential opioid misuse among individuals prescribed long-term therapy on tramadol, short-acting hydrocodone or short-acting oxycodone. METHODS: A retrospective cohort study was conducted using Arkansas All-Payer Claims Database (APCD; 2013-2018) linked to Arkansas Prescription Drug Monitoring Program (PDMP; 2014-2017) and state death certificate data (2013-2018). The study subjects were ambulatory, cancer-free adults with incident long-term therapy on tramadol, short-acting hydrocodone or short-acting oxycodone. The number of opioid prescribers/pharmacies, cash payment for opioid prescriptions, overlapping prescribers/pharmacies and a composite misuse score (derived from opioid prescribers/pharmacies and cash payment) were assessed in two 180 day windows as potential measures of misuse. The composite score was developed based on associations observed with opioid overdose and opioid-related injuries. RESULTS: A total of 17,816 (tramadol), 23,660 (hydrocodone) and 4799 (oxycodone) persons were included. The composite score had modest discrimination for overdose (c-index = 0.65). In the first 180 day period, the average composite misuse scores were 1.28 (tramadol), 1.93 (hydrocodone) and 2.18 (oxycodone). Compared to long-term hydrocodone, long-term tramadol had lower misuse (IRR [95% CI]: 0.75 [0.73-0.76]), and long-term oxycodone had higher misuse (1.09 [1.07-1.11]) in adjusted analyses. Qualitatively similar associations were observed for nearly all individual component measures of misuse. CONCLUSION: A composite measure of potential opioid misuse had modest levels of discrimination in detecting overdose. In comparison to long-term hydrocodone therapy, long-term oxycodone had higher and tramadol had lower risk of potential opioid misuse.


Assuntos
Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Tramadol , Adulto , Humanos , Hidrocodona/efeitos adversos , Tramadol/efeitos adversos , Oxicodona/efeitos adversos , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Arkansas/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Overdose de Drogas/tratamento farmacológico
12.
J Emerg Med ; 63(1): e28-e30, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35940982

RESUMO

BACKGROUND: Kratom (Mitragyna speciosa), an evergreen tree native to Southeast Asia, contains alkaloids that cause both stimulant and opioid-like effects. In the United States, its use continues to grow. Kratom products, however, are unregulated and nonstandardized, and reports of adulteration have been described previously. CASE REPORT: A 21-year-old African-American woman with a history of occasional headaches and self-treatment with internet-purchased kratom presented to the emergency department with the chief symptoms of nausea, vomiting, and left flank pain. Laboratory tests showed a markedly elevated serum creatinine of 4.25 mg/dL (reference range 0.6-1.2 mg/dL) and proteinuria. A computed tomography scan of the abdomen and pelvis was unrevealing. A standard urine screen for drugs of abuse was positive for opiates. A confirmatory testing revealed the presence of hydrocodone and morphine in the urine. Hydrocodone, morphine, and mitragynine were identified in a sample of kratom leaves provided by the patient. The patient's renal function improved with supportive care and normalized 1 month post discharge after kratom discontinuation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite widespread use, relatively little is known about kratom's adverse effects, particularly regarding its potential to cause renal insufficiency. This case illustrates the vital importance of recognizing that adulteration of unregulated products is certainly a possibility and clinicians may continue to see a rise in adverse effects, given kratom's increasing popularity.


Assuntos
Injúria Renal Aguda , Mitragyna , Injúria Renal Aguda/induzido quimicamente , Adulto , Assistência ao Convalescente , Analgésicos Opioides/efeitos adversos , Creatinina , Feminino , Humanos , Hidrocodona/efeitos adversos , Mitragyna/efeitos adversos , Morfina , Alta do Paciente , Estados Unidos , Adulto Jovem
13.
Clin Transl Sci ; 15(10): 2479-2492, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35899435

RESUMO

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.


Assuntos
Dor Aguda , Analgésicos Opioides , Dor Pós-Operatória , Humanos , Dor Aguda/diagnóstico , Dor Aguda/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Codeína/administração & dosagem , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Hidrocodona/administração & dosagem , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica , Estudos Prospectivos , Tramadol/administração & dosagem
14.
Pediatr Emerg Care ; 38(8): 363-366, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35802483

RESUMO

OBJECTIVES: Painful infectious mouth conditions such as herpangina, hand-foot-and-mouth disease, and herpetic gingivostomatitis can cause pain, dehydration, and hospitalization in young children. Treatment for these conditions is generally supportive and directed toward pain relief from ulcerative lesions, thus facilitating oral intake, and preventing dehydration. Attempts at oral therapy at home and in the emergency department are often refused and immediately spit back out. This study evaluated the efficacy of intranasal fentanyl (INF) compared with a commonly used oral (PO) acetaminophen/hydrocodone formulation for the treatment of children with painful infectious mouth conditions. METHODS: This study was a prospective, nonblinded, randomized controlled noninferiority trial conducted in an academic tertiary care pediatric emergency department. The study enrolled children between the ages of 6 months and 18 years with painful infectious mouth lesions and poor oral intake. Patients were randomized to receive either INF (1.5 µg/kg, intervention) or PO acetaminophen/hydrocodone (0.15 mg/kg, control) based on the dose of hydrocodone. The primary outcome was volume of fluid intake per body weight (in milliliters per kilogram) 60 minutes after analgesic administration. Secondary outcomes included pain scores using a validated visual assessment scale (VAS; 1, no pain; 10, worst pain), hydration score (VAS; 1, well hydrated; 4, very dehydrated), admission rate and overall satisfaction score (VAS; 1, worst; 7, best). A priori power analysis indicated that 34 patients would achieve an 81% power with an α value of 0.05. RESULTS: Of the 34 patients enrolled, 17 were randomized to INF and 17 to PO. The demographics between both groups were similar in age, weight, sex, and race. There were no significant differences in parental perception of pain ( P = 0.69) or hydration status ( P = 0.78). Oral fluid intake at 60 minutes was 20 mL/kg for INF versus 18 mL/kg for PO ( P = 0.53). Pain scores at 15 and 30 minutes were 1.7 versus 2.9 ( P = 0.09) and 0.6 versus 1.6 ( P = 0.59). Parental perceptions of pain and hydration status at 60 minutes were 2.2 versus 2.4 ( P = 0.77) and 1.7 versus 1.5 ( P = 0.37). Overall parental satisfaction was 6.4 for INF versus 6.5 for PO ( P = 0.71), and admission rate was 0 vs 12% ( P = 0.49). There were no adverse events such as respiratory, cardiac, or central nervous system depression in either group. CONCLUSIONS: Intranasal fentanyl seems to be a safe and effective alternative to acetaminophen with hydrocodone in reducing pain and improving hydration status in children with painful infectious mouth lesions and poor oral intake.


Assuntos
Doenças Transmissíveis , Fentanila , Acetaminofen/uso terapêutico , Administração Intranasal , Analgésicos Opioides , Criança , Pré-Escolar , Desidratação/complicações , Método Duplo-Cego , Humanos , Hidrocodona/uso terapêutico , Lactente , Dor/tratamento farmacológico , Dor/etiologia , Manejo da Dor , Medição da Dor , Estudos Prospectivos
15.
Neurology ; 99(13): e1432-e1442, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35835561

RESUMO

BACKGROUND AND OBJECTIVES: The concomitant use of prescription opioids and skeletal muscle relaxants has been associated with opioid overdose, but little data exist on the head-to-head safety of these drug combinations. The objective of this study was to compare the risk of opioid overdose among patients on long-term opioid therapy who concurrently initiate skeletal muscle relaxants. METHODS: We conducted an active comparator cohort study spanning 2000 to 2019 using healthcare utilization data from 4 US commercial and public insurance databases. Individuals were required to have at least 180 days of continuous enrollment and at least 90 days of continuous prescription opioid use immediately before and on the date of skeletal muscle relaxant initiation. Exposures were the concomitant use of prescription opioids and skeletal muscle relaxants, and the main outcome was the hazard ratio (HR) and bootstrapped 95% CI of opioid overdose resulting in an emergency department visit or hospitalization. The primary analysis quantified opioid overdose risk across 7 prescription opioid-skeletal muscle relaxant therapies and a negative control outcome (sepsis) to assess potential confounding by unmeasured illicit opioid use. Secondary analyses evaluated two-group and five-group comparisons in patients with similar baseline characteristics; individuals without previous recorded substance abuse; and subgroups stratified by baseline opioid dosage, benzodiazepine codispensing, and oxycodone or hydrocodone use. RESULTS: Weighted HR of opioid overdose relative to cyclobenzaprine was 2.52 (95% CI 1.29-4.90) for baclofen; 1.64 (95% CI 0.81-3.34) for carisoprodol; 1.14 (95% CI 0.53-2.46) for chlorzoxazone/orphenadrine; 0.46 (95% CI 0.17-1.24) for metaxalone; 1.00 (95% CI 0.45-2.20) for methocarbamol; and 1.07 (95% CI 0.49-2.33) for tizanidine in the 30-day intention-to-treat analysis. Findings were similar in the as-treated analysis, 2-group and 5-group comparisons, and patients without previous recorded substance abuse. None of the therapies relative to cyclobenzaprine were associated with sepsis, and no subgroups indicated an increased risk of opioid overdose. DISCUSSION: Concomitant use of prescription opioids and baclofen relative to cyclobenzaprine is associated with opioid overdose. Clinical interventions may focus on prescribing alternatives in the same drug class or providing access to opioid antagonists if treatment with both medications is necessary for pain management.


Assuntos
Carisoprodol , Metocarbamol , Fármacos Neuromusculares , Overdose de Opiáceos , Sepse , Transtornos Relacionados ao Uso de Substâncias , Amitriptilina/análogos & derivados , Analgésicos Opioides , Baclofeno , Benzodiazepinas/efeitos adversos , Clorzoxazona , Estudos de Coortes , Humanos , Hidrocodona , Antagonistas de Entorpecentes/uso terapêutico , Fármacos Neuromusculares/efeitos adversos , Orfenadrina , Oxicodona , Prescrições , Sepse/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico
16.
Clin Genitourin Cancer ; 20(5): e419-e423, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35705450

RESUMO

BACKGROUND: Veterans have disproportionate risk of opioid misuse and abuse compared to the civilian population. Managing acute postoperative pain without opioids is of the utmost importance for the Veteran patient population. This pilot study evaluates a novel multimodal opioid-free pain control regimen by assessing postoperative pain in Veterans undergoing robotic-assisted radical prostatectomy (RARP). METHODS: Prospective data was collected from patients undergoing RARP at a Department of Veterans Affairs Medical Center. Patients in the opioid-cohort received tramadol, hydrocodone-acetaminophen, or oxycodone-acetaminophen postoperatively. The opioid-free novel multimodal approach consisted of 100 mg gabapentin TID, 15 mg ketorolac Q6 hours, and 1 mg scheduled IV acetaminophen Q6 hours. Pain scores were collected using a visual analogue pain scale on postoperative days 0 and 1. RESULTS: Data was collected from 57 patients, 33 treated with opioids and 24 with the opioid-free pathway. There were no significant differences in demographics (P > .05) between cohorts. No significant differences were observed for preoperative and intraoperative variables (P > .05). Average postoperative day 0 pain scores for opioid-free (2.2 ± 3.1) and opioid treatments (3.1 ± 3.1) were not statistically different (P = .1321). Postoperative day 1 differences of average pain scores for opioid-free (0.9 ± 1.9) and opioid (1.6 ± 3.1) treatments were not statistically significant (P = .1647). CONCLUSIONS: The novel multimodal opioid-free treatment in this study may be effectively utilized for postoperative pain during hospital recovery of Veterans undergoing RARP. Future directions include a randomized control clinical trial in the general population.


Assuntos
Procedimentos Cirúrgicos Robóticos , Tramadol , Veteranos , Acetaminofen/uso terapêutico , Analgésicos Opioides/uso terapêutico , Gabapentina , Humanos , Hidrocodona/uso terapêutico , Cetorolaco/uso terapêutico , Masculino , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Projetos Piloto , Estudos Prospectivos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tramadol/uso terapêutico
17.
Infect Genet Evol ; 103: 105318, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35718334

RESUMO

COVID-19 pathogenesis is mainly attributed to dysregulated antiviral immune response, the prominent hallmark of COVID-19. As no established drugs are available against SARS-CoV-2 and developing new ones would be a big challenge, repurposing of existing drugs holds promise against COVID-19. Here, we used a signature-based strategy to delve into cellular responses to SARS-CoV-2 infection in order to identify potential host contributors in COVID-19 pathogenesis and to find repurposable drugs using in silico approaches. We scrutinized transcriptomic profile of various human alveolar cell sources infected with SARS-CoV-2 to determine up-regulated genes specific to COVID-19. Enrichment analysis revealed that the up-regulated genes were involved mainly in viral infectious disease, immune system, and signal transduction pathways. Analysis of protein-protein interaction network and COVID-19 molecular pathway resulted in identifying several anti-viral proteins as well as 11 host pro-viral proteins, ADAR, HBEGF, MMP9, USP18, JUN, FOS, IRF2, ICAM1, IFI35, CASP1, and STAT3. Finally, molecular docking of up-regulated proteins and all FDA-approved drugs revealed that both Hydrocortisone and Benzhydrocodone possess high binding affinity for all pro-viral proteins. The suggested repurposed drugs should be subject to complementary in vitro and in vivo experiments in order to be evaluated in detail prior to clinical studies in potential management of COVID-19.


Assuntos
Antivirais , Hidrocodona , Hidrocortisona , SARS-CoV-2 , Antivirais/farmacologia , Reposicionamento de Medicamentos , Humanos , Hidrocodona/análogos & derivados , Hidrocodona/farmacologia , Hidrocortisona/farmacologia , Simulação de Acoplamento Molecular , SARS-CoV-2/efeitos dos fármacos , Transcriptoma
18.
J Opioid Manag ; 18(3): 205-221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35666477

RESUMO

OBJECTIVES: To quantify the prevalence of opioid drug dependence and abuse in United States between 2017 and 2018 and identify which opioid molecules are associated with a higher level of dependence and abuse. DESIGN: National Survey on Drug Use and Health (NSDUH) data for 2017 and 2018 have been extracted. The variables related to painkillers were studied, the most important ones were selected, and several variable crosses were made. After the data were extracted, they were analyzed using Microsoft Excel and PivotTables, calculating the relative prevalence and percentages of patients with abuse and dependence. RESULTS: In total, 1.4 million people had dependence on pain relievers (PRs) in 2018. The last PR used was mostly hydrocodone (33 percent) and oxycodone (24 percent). The main reasons for using a PR without a doctor's prescription were relieving pain (48 percent), feel good (16 percent), and relax or relieve tension (15 percent). Among patients who used a PR with a medical prescription, 1.5 million used it more frequently than prescribed, 1.2 million used it longer than prescribed, and 1.9 million used it in higher amounts than prescribed. CONCLUSIONS: Abuse and dependence to PRs is lower than expected with over 1.4 million people in the United States having dependence in 2018 (0.6 percent point prevalence). Most cases of dependence are associated with misuse or abuse of prescriptions without medical supervision or the use of medications without a prescription of their own. Oxycodone and hydrocodone are the molecules most associated with dependence, misuse, abuse, and use without prescription. The age of onset of oxycodone misuse is very early (14 years old). Fentanyl does not seem relevant in any of the variables studied.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Uso Indevido de Medicamentos sob Prescrição , Adolescente , Analgésicos Opioides/efeitos adversos , Humanos , Hidrocodona/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Oxicodona/efeitos adversos , Dor/tratamento farmacológico , Prevalência , Estados Unidos/epidemiologia
19.
J Anal Toxicol ; 46(8): 899-904, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-35640884

RESUMO

A rapid, simple extraction method followed by qualitative screening using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for drugs in oral fluid is presented. The decision points were selected to be at, or lower, than those recommended as Tier I compounds by the National Safety Council's Alcohol, Drugs and Impairment Division for toxicological investigation of driving under the influence of drug (DUID) cases and were also at, or lower, than those recommended by Substance Abuse and Mental Health Service Administration and the Department of Transportation for Federal workplace drug testing programs. The method included 30 drugs: delta-9-tetrahydrocannabinol, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, cocaine, benzoylecgonine, carisoprodol, meprobamate, zolpidem, alprazolam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, lorazepam, oxazepam, temazepam, codeine, morphine, 6-acetylmorphine, buprenorphine, fentanyl, hydrocodone, hydromorphone, oxycodone, oxymorphone, methadone, tramadol and phencyclidine. Phencyclidine was included because it is in the Federal workplace program even though it is considered a Tier II drug for DUID cases. A liquid-liquid extraction method using isopropanol, hexane and ethyl acetate to extract drugs from the oral fluid-buffer mix collected in a Quantisal™ device, followed by LC-MS-MS screening, was developed and validated according to ANSI/ASB 2019 Standard Practices for Method Validation in Forensic Toxicology. Interference studies, limit of detection, precision at the decision point, ionization suppression/enhancement and processed sample stability were determined for each drug. The method was successfully applied to proficiency specimens and routine samples received in the laboratory.


Assuntos
3,4-Metilenodioxianfetamina , Buprenorfina , Carisoprodol , Cocaína , Meprobamato , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Tramadol , 2-Propanol , Alprazolam , Anfetaminas , Clonazepam , Codeína , Dronabinol , Fentanila , Hexanos , Hidrocodona , Hidromorfona , Lorazepam , Metadona , Derivados da Morfina , Nordazepam , Oxazepam , Oxicodona , Oximorfona , Preparações Farmacêuticas/análise , Fenciclidina , Espectrometria de Massas em Tandem , Temazepam , Zolpidem
20.
J Anal Toxicol ; 46(7): 697-704, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35639619

RESUMO

To avoid a positive urine drug test, donors might try to subvert the test, either by adulterating the specimen with a product designed to interfere with testing or by substituting the specimen for a synthetic urine. A market search conducted in December of 2020 identified 3 adulterants and 32 synthetic urines, and a selection was procured based on specific criteria. Samples prepared with the 3 adulterants and 10 synthetic urines were submitted for testing at five forensic drug testing laboratories to perform immunoassay screening, chromatographic confirmation analysis and specimen validity testing (SVT). One adulterant determined to contain iodate reduced THC-COOH concentrations by 65% and the concentrations of 6-acetylmorphine, morphine, oxycodone, oxymorphone, hydrocodone and hydromorphone by 6-27%. Another adulterant determined to contain nitrite reduced THC-COOH concentrations by 22%, while the third did not affect drug screening or confirmatory testing. Both active adulterants could be identified through positive oxidant screens as well as through signal suppression in cloned enzyme donor immunoassay (CEDIA). The synthetic urines could not be identified either through traditional SVT or by the AdultaCheck10 dipstick. The Synthetic UrineCheck dipstick produced a difference in response between the authentic urine specimen and the synthetic urine samples, but the difference was small and difficult to observe. While most synthetic urines now contain uric acid, magnesium and caffeine, the results indicated that a biomarker panel including endogenous and exogenous markers of authentic urine performed well and clearly demonstrated the absence of biomarkers in the synthetic urines. The SVT assay also offers potential targets for future screening assays.


Assuntos
Dronabinol , Detecção do Abuso de Substâncias , Hidrocodona , Imunoensaio , Oximorfona , Detecção do Abuso de Substâncias/métodos
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