Buprenorphine blood concentrations: A biomarker for analgesia

2021 ◽  
Vol 17 (7) ◽  
pp. 15-20
Author(s):  
Michael Guarnieri, PhD, MPH
Keyword(s):  
Clinical Evidence ◽  
Acute Postoperative Pain ◽  
Blood Concentrations ◽  
Patient Reports ◽  
Drug Concentrations ◽  
Subjective Pain ◽  
Nonopioid Analgesics ◽  
Pain Reports ◽  
Quantitative Sensory Tests ◽  
Sensory Tests

Opioids, the frontline drugs for postsurgical analgesia, have been linked to diversion and abuse with lethal consequences. The search for safe analgesics with less harm potential has been decades long. However, clinical trials for safe opioid and nonopioid analgesics have relied on subjective pain reports, which are biased by placebo effects that increase the complexity of trials to develop new therapies to manage pain.Research in opioid naïve animals and humans demonstrates that blood concentrations of opioids that effectively saturate the morphine opioid receptor are tightly linked with patient reports and quantitative sensory tests for analgesia. Opioid drug concentrations can predict clinical responses.This report reviews preclinical and clinical evidence correlating buprenorphine pharmacokinetics with analgesia. More than 30 years of data confirm buprenorphine blood concentrations can be an objective biomarker of analgesia for moderate to severe acute postoperative pain.

scholarly journals Measurement Error of a Simplified Protocol for Quantitative Sensory Tests in Chronic Pain Patients

2017 ◽  
Vol 42 (5) ◽  
pp. 660-668 ◽  
Author(s):  
Monika Müller ◽  
José Alberto Biurrun Manresa ◽  
Andreas Limacher ◽  
Konrad Streitberger ◽  
Peter Jüni ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Measurement Error ◽  
Chronic Pain Patients ◽  
Quantitative Sensory Tests ◽  
Pain Patients ◽  
Sensory Tests

scholarly journals Laboratory Personnel Gender and Cold Pressor Apparatus Affect Subjective Pain Reports

2014 ◽  
Vol 19 (1) ◽  
pp. e13-e18 ◽  
Author(s):  
Jacob M Vigil ◽  
Lauren N Rowell ◽  
Joe Alcock ◽  
Randy Maestes
Keyword(s):  
Pain Sensitivity ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Pain Tolerance ◽  
Cold Pain ◽  
Laboratory Personnel ◽  
Subjective Pain ◽  
Lower Pain ◽  
Pain Reporting ◽  
Pain Reports

BACKGROUND: There is no standardized method for cold pressor pain tasks across experiments. Temperature, apparatus and aspects of experimenters vary widely among studies. It is well known that experimental pain tolerance is influenced by setting as well as the sex of the experimenter. It is not known whether other contextual factors influence experimental pain reporting.OBJECTIVES: The present two-part experiment examines whether minimizing and standardizing interactions with laboratory personnel (eg, limiting interaction with participants to consenting and questions and not during the actual pain task) eliminates the influence of examiner characteristics on subjective pain reports and whether using different cold pain apparatus (cooler versus machine) influences reports.METHODS:The present experiment manipulated the gender of the experimenter (male, female and transgender) and the type of cold pressor task (CPT) apparatus (ice cooler versus refrigerated bath circulator). Participants conducted the CPT at one of two pain levels (5°C or 16°C) without an experimenter present.RESULTS:Men and women showed lower pain sensitivity when they were processed by biological male personnel than by biological female personnel before the CPT. Women who interacted with a transgendered researcher likewise reported higher pain sensitivity than women processed by biological male or female researchers. The type of CPT apparatus, despite operating at equivalent temperatures, also influenced subjective pain reports.DISCUSSION: The findings show that even minimal interactions with laboratory personnel who differ in gender, and differences in laboratory materials impact the reliable measurement of pain.CONCLUSION: More standardized protocols for measuring pain across varying research and clinical settings should be developed.

scholarly journals Methadone, Buprenorphine, Oxycodone, Fentanyl, and Tramadol in Multiple Postmortem Matrices

2021 ◽  
Author(s):  
Stine Marie Havig ◽  
Vigdis Vindenes ◽  
Åse Marit Leere Øiestad ◽  
Sidsel Rogde ◽  
Cecilie Hasselø Thaulow
Keyword(s):  
Peripheral Blood ◽  
Vitreous Humor ◽  
Pericardial Fluid ◽  
Limited Information ◽  
Blood Concentrations ◽  
Bodily Fluids ◽  
Drug Concentrations ◽  
Quantitative Analyses ◽  
Alternative Matrices ◽  
Almost All

Abstract Peripheral blood concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid, muscle, and vitreous humor have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl, and tramadol in postmortem samples of pericardial fluid, skeletal muscle, and vitreous humor, in addition to peripheral and cardiac blood; and if drug concentrations in these alternative matrices were comparable to those in peripheral blood, and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl, and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except for in vitreous humor, were relatively similar to those in peripheral blood. Larger variations in concentrations were found for buprenorphine, oxycodone, and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but interpretation of quantitative results must be performed with caution.

Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases

Lupus ◽  
1996 ◽  
Vol 5 (1_suppl) ◽  
pp. 11-15 ◽  
Author(s):  
Daniel E Furst
Keyword(s):  
Protein Binding ◽  
Mononuclear Cells ◽  
Morning Stiffness ◽  
Pharmacokinetic Interaction ◽  
Great Variability ◽  
Severe Malnutrition ◽  
Blood Clearance ◽  
Blood Concentrations ◽  
Drug Concentrations ◽  
Differential Binding

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well absorbed (0.7-0.8 bioavailability) when given orally. Severe malnutrition (such as kwashiorkor) effects absorption but diahrrea does not. Both HCQ and CQ have prolonged half-lives, between 40 and 50 days, and low blood clearance (e.g. hydroxychloroquine's blood clearance is 96 ml/min). There is great variability of blood concentrations with an eleven-fold range of drug concentrations found after similar doses in RA patients. Protein binding ranges between 30 and 40% with binding to both albumin and alpha1 glycoprotein. There is differential binding and metabolism of the (R) and (S) stereoisomers. Both drugs bind strongly to pigmented tissues but also bind to mononuclear cells, muscles, etc. There is stereo-selective excretion of both drugs and 40-50% of the drug is excreted renally. Between 21 and 47% is excreted unchanged. There is a suggestion of concentration response and concentration toxicity relationships with decreased morning stiffness as HCQ concentrations increase and increased EKG abnormalities as CQ concentrations become higher, but further testing is required. Pharmacokinetic interaction studies are limited. Potentially important kinetic interactions have been documented for d-penicillamine and cimetidine but have not been found for aspirin, ranitidine or imipramine.

scholarly journals Repeatability of quantitative sensory testing in healthy cats in a clinical setting with comparison to cats with osteoarthritis

2017 ◽  
Vol 19 (12) ◽  
pp. 1274-1282 ◽  
Author(s):  
Elena S Addison ◽  
Dylan N Clements
Keyword(s):  
Clinical Setting ◽  
Thermal Sensitivity ◽  
Sensory Threshold ◽  
Vertical Force ◽  
Sensory Testing ◽  
Sensitivity Testing ◽  
Threshold Testing ◽  
Quantitative Sensory Tests ◽  
Sensory Tests ◽  
Plate System

Objectives The aim of this study was to evaluate the repeatability of quantitative sensory tests (QSTs) in a group of healthy untrained cats (n = 14) and to compare the results with those from cats with osteoarthritis (n = 7). Methods Peak vertical force (PVF) and vertical impulse were measured on a pressure plate system. Thermal sensitivity was assessed using a temperature-controlled plate at 7°C and 40°C. Individual paw lifts and overall duration of paw lifts were counted and measured for each limb. Paw withdrawal thresholds were measured using manual and electronic von Frey monofilaments (MVF and EVF, respectively) applied to the metacarpal or metatarsal pads. All measurements were repeated twice to assess repeatability of the tests. Results In healthy cats all tests were moderately repeatable. When compared with cats with osteoarthritis the PVF was significantly higher in healthy hindlimbs in repeat 1 but not in repeat 2. Cats with osteoarthritis of the forelimbs showed a decrease in the frequency of paw lifts on the 7°C plate compared with cats with healthy forelimbs, and the duration of paw lifts was significantly less than healthy forelimbs in the first repeat but not in the second repeat. Osteoarthritic limbs had significantly lower paw withdrawal thresholds with both MVF and EVF than healthy limbs. Conclusions and relevance QSTs are moderately repeatable in untrained cats. Kinetic gait analysis did not permit differentiation between healthy limbs and those with osteoarthritis, but thermal sensitivity testing (cold) does. Sensory threshold testing can differentiate osteoarthritic and healthy limbs, and may be useful in the diagnosis and monitoring of this condition in cats in the clinical setting.

Opiate-induced Rhabdomyolysis

1985 ◽  
Vol 4 (1) ◽  
pp. 71-74 ◽  
Author(s):  
P.G. Blain ◽  
R.J.M. Lane ◽  
D.N. Bateman ◽  
M.D. Rawlins
Keyword(s):  
Renal Failure ◽  
Creatine Kinase ◽  
Acute Renal Failure ◽  
Clinical Evidence ◽  
Elevated Serum ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Serum Aspartate Aminotransferase ◽  
Plasma Drug Concentrations ◽  
Serum Myoglobin

Three patients with opiate self-poisoning developed acute muscle damage with elevated serum aspartate aminotransferase and creatine kinase activities, increased serum myoglobin concentrations, raised plasma creatinine concentrations, hypocalcaemia and hyperphosphataemia. These abnormalities gradually resolved over 7-10 days, but recovery was complicated due to the development of acute renal failure (requiring haemodialysis) in one patient. Plasma drug concentrations, shortly after admission, in the patients taking dihydrocodeine and morphine were grossly elevated (184 and 60 μg/l respectively). Clinical evidence of myopathy was minimal in all three patients and muscle biopsy of one patient was normal at 7 days.

Quantitative sensory tests in patients with neuralgia 11 to 25 years after injury

Pain ◽  
1992 ◽  
Vol 48 (2) ◽  
pp. 237-244 ◽  
Author(s):  
Lis Karin Wahren ◽  
Erik Torebjörk
Keyword(s):  
Quantitative Sensory Tests ◽  
Sensory Tests

scholarly journals Quantitative sensory tests (perceptual thresholds) in patients with spinal cord injury

2007 ◽  
Vol 44 (1) ◽  
pp. 77 ◽  
Author(s):  
Gordana Savic ◽  
Ebba M. K. Bergstrm ◽  
Nick J. Davey ◽  
Peter H. Ellaway ◽  
Hans L. Frankel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cord Injury ◽  
Quantitative Sensory Tests ◽  
Sensory Tests

scholarly journals Therapeutic Reference Ranges for Psychotropic Drugs: A Protocol for Systematic Reviews

2021 ◽  
Vol 12 ◽  
Author(s):  
Xenia M. Hart ◽  
Luzie Eichentopf ◽  
Xenija Lense ◽  
Thomas Riemer ◽  
Katja Wesner ◽  
...  
Keyword(s):  
Psychotropic Drug ◽  
Psychotropic Drugs ◽  
Drug Monitoring ◽  
Photon Emission ◽  
Therapeutic Drug ◽  
Emission Computed Tomography ◽  
Clinical Effects ◽  
Reference Ranges ◽  
Blood Concentrations ◽  
Drug Concentrations

Background: For many psychotropic drugs, monitoring of drug concentrations in the blood (Therapeutic Drug Monitoring; TDM) has been proven useful to individualize treatments and optimize drug effects. Clinicians hereby compare individual drug concentrations to population-based reference ranges for a titration of prescribed doses. Thus, established reference ranges are pre-requisite for TDM. For psychotropic drugs, guideline-based ranges are mostly expert recommendations derived from a conglomerate of cohort and cross-sectional studies. A systematic approach for identifying therapeutic reference ranges has not been published yet. This paper describes how to search, evaluate and grade the available literature and validate published therapeutic reference ranges for psychotropic drugs.Methods/Results: Following PRISMA guidelines, relevant databases have to be systematically searched using search terms for the specific psychotropic drug, blood concentrations, drug monitoring, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The search should be restricted to humans, and diagnoses should be pre-specified. Therapeutic references ranges will not only base upon studies that report blood concentrations in relation to clinical effects, but will also include implications from neuroimaging studies on target engagement. Furthermore, studies reporting concentrations in representative patient populations are used to support identified ranges. Each range will be assigned a level of underlying evidence according to a systematic grading system.Discussion: Following this protocol allows a comprehensive overview of TDM literature that supports a certain reference range for a psychotropic drug. The assigned level of evidence reflects the validity of a reported range rather than experts' opinions.

scholarly journals Effect of sample heating on results of therapeutic drug monitoring

2021 ◽  
Vol 45 (3) ◽  
pp. 183-187
Author(s):  
Dao-Hai Cheng ◽  
Zhen-Guang Huang ◽  
Jing-Bing Zhu
Keyword(s):  
Heat Treatment ◽  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Heating ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Therapeutic Drugs ◽  
Drug Concentrations

Abstract Objectives Heat treatment is a convenient measure for pathogens inactivation. The authors investigated the effects of this method on blood concentrations of six commonly therapeutic drugs. Methods Plasma and whole blood were pretreated with or without heating at 56 °C for 30 min, and drug concentrations of vancomycin, methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine were examined. Results Increased valproic acid levels after plasma heating (63.2 ± 30.2 vs. 62.1 ± 29.8 mg/L, mean recovery 102.0%) and whole blood heating (64.5 ± 30.5 vs. 62.1 ± 29.8 mg/L, mean recovery 104.6%) were observed (both p<0.05), but these differences were not considered clinically important. Recoveries of vancomycin in heat treatments varied widely, with an average and significant decrease of 15.8% in value after whole blood heating (11.7 ± 8.1 vs. 13.7 ± 8.6 mg/L, p<0.05). Conclusions Plasma or whole blood heating at 56 °C for 30 min are feasible in pathogens inactivation during monitoring methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine. However, such pretreatment seems inappropriate in monitoring vancomycin concentrations. Those results highlight the need for caution when applying heat treatment for pathogens inactivation in therapeutic drug monitoring.

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