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Journal of Addiction MedicineThis narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly... (Review)
Review
OBJECTIVES
This narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly manufactured fentanyl (IMF).
RESULTS
Fentanyl is highly lipophilic, lending itself to rapid absorption by highly perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as "fentanyl rebound." Clinical implications in overdose (respiratory depression, muscle rigidity, and "wooden chest syndrome") and opioid use disorder treatment (subjective effects, withdrawal, and buprenorphine-precipitated withdrawal) are discussed. The authors highlight research gaps derived from differences in medicinal fentanyl studies and IMF use patterns, including that medicinal fentanyl studies are largely conducted with persons who were opioid-naive, anesthetized, or had severe chronic pain and that IMF use is characterized by supratherapeutic doses and frequent and sustained administration patterns, as well as adulteration with other substances and/or fentanyl analogs.
CONCLUSIONS
This review reexamines information yielded from decades of medicinal fentanyl research and applies elements of the pharmacokinetic profile to persons with IMF exposure. In persons who use drugs, peripheral accumulation of fentanyl may be leading to prolonged exposure. More focused research on the pharmacology of fentanyl in persons using IMF is warranted.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Clinical Relevance; Drug Overdose; Fentanyl
PubMed: 37788600
DOI: 10.1097/ADM.0000000000001185 -
Anesthesiology Jan 2024Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering...
BACKGROUND
Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH susceptibility gene, in unselected populations. The authors sought to identify the rate of MH features or fulminant episodes after triggering agent exposure in an unselected population undergoing genomic screening including actionable RYR1 variants.
METHODS
The MyCode Community Health Initiative by Geisinger (USA) is an electronic health record-linked biobank that discloses pathogenic and likely pathogenic variants in clinically actionable genes to patient-participants. Available electronic anesthesia and ambulatory records for participants with actionable RYR1 results returned through December 2020 were evaluated for pertinent findings via double-coded chart reviews and reconciliation. Descriptive statistics for observed phenotypes were calculated.
RESULTS
One hundred fifty-two participants had an actionable RYR1 variant disclosed during the study period. None had previous documented genetic testing for MH susceptibility; one had previous contracture testing diagnosing MH susceptibility. Sixty-eight participants (44.7%) had anesthesia records documenting triggering agent exposure during at least one procedure. None received dantrolene treatment or had documented muscle rigidity, myoglobinuria, hyperkalemia, elevated creatine kinase, severe myalgia, or tea-colored urine. Of 120 possibly MH-related findings (postoperative intensive care unit admissions, hyperthermia, arterial blood gas evaluation, hypercapnia, or tachycardia), 112 (93.3%) were deemed unlikely to be MH events; 8 (6.7%) had insufficient records to determine etiology.
CONCLUSIONS
Results demonstrate a low frequency of classic intraanesthetic hypermetabolic phenotypes in an unselected population with actionable RYR1 variants. Further research on the actionability of screening for MH susceptibility in unselected populations, including economic impact, predictors of MH episodes, and expanded clinical phenotypes, is necessary.
Topics: Humans; Genetic Testing; Malignant Hyperthermia; Metagenomics; Mutation; Phenotype; Ryanodine Receptor Calcium Release Channel
PubMed: 37787745
DOI: 10.1097/ALN.0000000000004786 -
Cureus Aug 2023Wooden chest syndrome (WCS) is a rare phenomenon of opioid-induced skeletal muscle rigidity causing respiratory failure and inability to ventilate. The most common...
Wooden chest syndrome (WCS) is a rare phenomenon of opioid-induced skeletal muscle rigidity causing respiratory failure and inability to ventilate. The most common opioid associated with WCS is the synthetic opioid fentanyl. Fentanyl has been called the deadliest drug in America. With the use of fentanyl in critical care units and operation rooms, it is important to better understand fentanyl's side effects and predisposing factors of WCS. The symptoms of WCS are often seen in lower fentanyl doses than what would cause apnea. In this case report, we present a case of WCS with an extremely low dose of fentanyl, i.e., 50 μcg (0.49 μcg/kg), in an 80-year-old patient with a medical history significant for chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS).
PubMed: 37731415
DOI: 10.7759/cureus.43788 -
Cureus Aug 2023This study presents the clinical features and disease progression of a 39-year-old male patient diagnosed with Huntington's disease (HD). The diagnosis was confirmed by...
This study presents the clinical features and disease progression of a 39-year-old male patient diagnosed with Huntington's disease (HD). The diagnosis was confirmed by direct genetic testing, using DNA obtained from a blood sample that revealed expanded cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HD gene). The patient exhibited motor symptoms, including chorea, muscle rigidity, coordination difficulties, and speech and swallowing impairments. Cognitive symptoms comprised impaired judgment, planning difficulties, slowed thinking, memory lapses, and attention problems. The patient's progressive deterioration resulted in wheelchair dependency and increased reliance on supportive care. This report highlights the significance of genetic testing in confirming HD diagnosis and emphasizes the need for a multidisciplinary approach to manage the symptoms and improve the patient's quality of life.
PubMed: 37700984
DOI: 10.7759/cureus.43377 -
Case Reports in Pediatrics 2023. Organophosphates are chemicals that lead to the accumulation of acetylcholine, causing muscarinic symptoms such as salivation and nicotinic manifestations like muscle...
. Organophosphates are chemicals that lead to the accumulation of acetylcholine, causing muscarinic symptoms such as salivation and nicotinic manifestations like muscle weakness and hypertension and rarely leading to basal ganglia impairment, manifesting as extrapyramidal symptoms. Literature reported that the use of amantadine, an amine that has both antiviral and dopaminergic activities, improves extrapyramidal manifestations. Most of the studies exploring the effect of amantadine were conducted on adults and there are extremely limited data in regards to this topic in Saudi Arabia. Thus, the purpose of this case study is to report the outcome of treating a child who developed extrapyramidal symptoms due to organophosphates poisoning with amantadine. . A 6-year-old boy was found by his family drowsy and drooling with an insecticide bottle beside him. He was brought to the ER and arrested on arrival, and he was eventually revived after 5 minutes of CPR. Then, he developed features of extrapyramidal involvement such as delirium, hyperactivity, akathisia, aphonia, and tremors. He was started on oral amantadine 50 mg once daily and then increased to twice daily for two weeks while admitted. During admission, his symptoms were assessed daily, and an improvement was noticed by his family and the medical team. Upon discharge, he was able to form sentences; tremors were almost resolved; and there was no rigidity or agitation. He was followed up postdischarge and showed significant improvement. He continued amantadine for almost 3 months until the full resolution of his symptoms. . This case illustrates the promising benefits of using amantadine in treating extrapyramidal manifestations following organophosphate ingestion.
PubMed: 37700928
DOI: 10.1155/2023/1632052 -
Medicina (Kaunas, Lithuania) Aug 2023: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo,... (Review)
Review
: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo, and temporomandibular disorders (TMDs). Previous studies reported that TMDs are more common in individuals with chronic whiplash-associated disorders (WAD) than in the general population; however, the pathophysiology and mechanism of this relationship are still not well understood. : A PubMed and Ovid EMBASE review was performed to identify all studies addressing the trauma related cause and effect relationship between WAD and TMDs from January 2003 to March 2023. : After screening for eligibility and inclusion criteria, a total of 16 articles met the selection criteria. The various included studies discussed different aspects of the association between WDA and TMDs, including changes in the coordination and amplitude of jaw opening, the severity of the associated symptoms/signs in cases of WAD, the degree of fatigue and psychological stress, difficulty in feeding, cervical and myofascial pain, changes in the MRI signal at various muscle points, muscle tenderness, and quality of life. : In this review, we summarized the clinical evidence of any trauma related cause and effect relationship between whiplash and TMDs. An accurate screening of the previous literature showed that, in conclusion, the relationship between whiplash and TMDs is still unclear.
Topics: Humans; Quality of Life; Temporomandibular Joint Disorders; Neck; Fatigue; Headache
PubMed: 37629772
DOI: 10.3390/medicina59081482 -
Digital Health 2023Sleep is vital to many processes involved in the well-being and health of children; however, it is estimated that 80% of children with Rett syndrome suffer from sleep...
Sleep is vital to many processes involved in the well-being and health of children; however, it is estimated that 80% of children with Rett syndrome suffer from sleep disorders. Caregiver reports and questionnaires, which are the current method of studying sleep, are prone to observer bias and missed information. Polysomnography is considered the gold standard for sleep analysis but is labor and cost-intensive and limits the frequency of data collection for sleep disorder studies. Wearable digital health technologies, such as actigraphy devices, have shown potential and feasibility as a method for sleep analysis in Rett syndrome, but have not been validated against polysomnography. Furthermore, the collected accelerometer data has limitations due to the rigidity, periodic limb movement, and involuntary muscle contractions prevalent in Rett syndrome. Heart rate and electrodermal activity, along with other physiological signals, have been linked to sleep stages and can be utilized with machine learning to provide better resistance to noise and false positives than actigraphy. This research aims to address the gap in Rett syndrome sleep analysis by comparing the performance of a machine learning model utilizing both accelerometer data and physiological data features to the gold-standard polysomnography for sleep analysis in Rett syndrome. Our analytical validation pilot study ( = 7) found that using physiological and accelerometer features, our machine learning models can differentiate between awake, non-rapid eye movement sleep, and rapid eye movement sleep in Rett syndrome children with an accuracy of 85.1% when using an individual model. Additionally, this work demonstrates that it is feasible to use digital health technologies in Rett syndrome, even at a young age, without data loss or interference from repetitive movements that are characteristic of Rett syndrome.
PubMed: 37545628
DOI: 10.1177/20552076231191622 -
Biomedicines Jul 2023Dopamine (DA) is the critical neurotransmitter involved in the unconscious control of muscle tone and body posture. We evaluated the general motor capacities and muscle...
Dopamine (DA) is the critical neurotransmitter involved in the unconscious control of muscle tone and body posture. We evaluated the general motor capacities and muscle responses to postural disturbance in three conditions: normal DA level (wild-type rats, WT), mild DA deficiency (WT after administration of α-methyl-p-tyrosine-AMPT, that blocks DA synthesis), and severe DA depletion (DAT-KO rats after AMPT). The horizontal displacements in WT rats elicited a multi-component EMG corrective response in the flexor and extensor muscles. Similar to the gradual progression of DA-related diseases, we observed different degrees of bradykinesia, rigidity, and postural instability after AMPT. The mild DA deficiency impaired the initiation pattern of corrective responses, specifically delaying the extensor muscles' activity ipsilaterally to displacement direction and earlier extensor activity from the opposite side. DA depletion in DAT-KO rats after AMPT elicited tremors, general stiffness, and akinesia, and caused earlier response to horizontal displacements in the coactivated flexor and extensor muscles bilaterally. The data obtained show the specific role of DA in postural reactions and suggest that this experimental approach can be used to investigate sensorimotor control in different dopamine-deficient states and to model DA-related diseases.
PubMed: 37509596
DOI: 10.3390/biomedicines11071958 -
Clinical Case Reports Jul 2023Serotonin syndrome can be a life-threatening condition that occurs from the overactivity of serotonin in the central nervous system. This report describes the use of...
Serotonin syndrome can be a life-threatening condition that occurs from the overactivity of serotonin in the central nervous system. This report describes the use of cyproheptadine for the management of serotonin syndrome in a patient taking fluoxetine and bupropion, who received methylene blue for vasoplegia syndrome. A 61-year-old female taking fluoxetine and bupropion preoperatively was given a total of three doses of methylene blue 100 mg IV within a brief time frame during and after a planned coronary artery bypass graft surgery. Postoperatively, the patient was not following commands, was agitated and confused, febrile with diaphoresis, tachycardic, had muscle rigidity, and horizontal ocular clonus. The patient's presentation was most consistent with serotonin syndrome due to a drug-drug interaction. Cyproheptadine and supportive care were used successfully to treat serotonin syndrome, and the patient was discharged home 14 days postoperatively. Based on the literature, there is no standardized method of weaning cyproheptadine when used for serotonin syndrome. The patient in our case received a total of 188 mg of cyproheptadine over the course of 10 days and did not experience any side effects. This case highlights a potential dosing regimen that can be used for other patients.
PubMed: 37476598
DOI: 10.1002/ccr3.7720