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Missouri Medicine 2019Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants.... (Review)
Review
Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants. It manifests as a hypermetabolic response resulting in tachycardia, tachypnea, hyperthermia, hypercapnia, acidosis, muscle rigidity and rhabdomyolysis. An increase in the end-tidal carbon dioxide is one of the earliest diagnostic signs. Dantrolene sodium is effective in the management of MH, and should be available whenever general anesthesia is administered. This review also aims to highlight the genetics and pathology of MH, along with its association with various inherited myopathy syndromes like central core disease, multi-mini core disease, Native-American myopathy, and King-Denborough syndrome.
Topics: Anesthetics; Dantrolene; Humans; Malignant Hyperthermia; Muscle Relaxants, Central; Neuromuscular Depolarizing Agents
PubMed: 31040503
DOI: No ID Found -
Toxins Apr 2021The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal... (Review)
Review
The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.
Topics: Animals; Brain; Dystonia; Humans; Muscle Contraction; Muscle Hypertonia; Muscle Rigidity; Muscle Spasticity; Muscle Tonus; Muscle, Skeletal; Neural Pathways; Spinal Cord
PubMed: 33923397
DOI: 10.3390/toxins13040282 -
Orphanet Journal of Rare Diseases Aug 2015Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as... (Review)
Review
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006.
Topics: Genetic Counseling; Humans; Malignant Hyperthermia
PubMed: 26238698
DOI: 10.1186/s13023-015-0310-1 -
British Journal of Pharmacology Apr 2023Fentanyl is a key therapeutic, used in anaesthesia and pain management. It is also increasingly used illicitly and is responsible for a large and growing number of... (Review)
Review
Fentanyl is a key therapeutic, used in anaesthesia and pain management. It is also increasingly used illicitly and is responsible for a large and growing number of opioid overdose deaths, especially in North America. A number of factors have been suggested to contribute to fentanyl's lethality, including rapid onset of action, in vivo potency, ligand bias, induction of muscle rigidity and reduced sensitivity to reversal by naloxone. Some of these factors can be considered to represent 'anomalous' pharmacological properties of fentanyl when compared with prototypical opioid agonists such as morphine. In this review, we examine the nature of fentanyl's 'anomalous' properties, to determine whether there is really a pharmacological basis to support the existence of such properties, and also discuss whether such properties are likely to contribute to overdose deaths involving fentanyls. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
Topics: Humans; Fentanyl; Analgesics, Opioid; Narcotic Antagonists; Naloxone; Drug Overdose
PubMed: 34030211
DOI: 10.1111/bph.15573 -
Internal Medicine (Tokyo, Japan) Jan 2020Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their... (Review)
Review
Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.
Topics: Deglutition; Deglutition Disorders; Disease Progression; Enteral Nutrition; Humans; Hypokinesia; Muscle Rigidity; Parkinson Disease; Pneumonia, Aspiration; Respiratory Aspiration; Stroke Rehabilitation
PubMed: 30996170
DOI: 10.2169/internalmedicine.2373-18 -
Advanced Emergency Nursing JournalMalignant hyperthermia (MH) is caused by a genetic disorder of the skeletal muscle that induces a hypermetabolic response when patients are exposed to a triggering agent... (Review)
Review
Malignant hyperthermia (MH) is caused by a genetic disorder of the skeletal muscle that induces a hypermetabolic response when patients are exposed to a triggering agent such as volatile inhaled anesthetics or depolarizing neuromuscular blockers. Symptoms of MH include increased carbon dioxide production, hyperthermia, muscle rigidity, tachypnea, tachycardia, acidosis, hyperkalemia, and rhabdomyolysis. Common scenarios for triggering agents are those used are during surgery and rapid sequence intubation. Hypermetabolic symptoms have a rapid onset; hence, prompt recognition and treatment are vital to prevent morbidity and mortality. The first-line treatment agent for an MH response is dantrolene. Further treatment includes managing complications related to a hypermetabolic response such as hyperkalemia and arrhythmias. This review is focused on the recognition and treatment considerations of MH in the emergency department to optimize therapy and improve patient morbidity and mortality.
Topics: Dantrolene; Diagnosis, Differential; Emergency Service, Hospital; Humans; Malignant Hyperthermia; Muscle Relaxants, Central; Risk Factors
PubMed: 33915557
DOI: 10.1097/TME.0000000000000344 -
Psychopharmacology Jun 2022In recent years, psychedelic substances with serotonergic mechanisms have accumulated substantial evidence that they may provide therapeutic benefits for people... (Review)
Review
RATIONALE
In recent years, psychedelic substances with serotonergic mechanisms have accumulated substantial evidence that they may provide therapeutic benefits for people suffering with psychiatric symptoms. Psychiatric disorders targeted by these psychedelic-assisted therapies are managed with serotonergic drugs like selective serotonin reuptake inhibitors (SSRIs) as the current standard of care, so it is important to evaluate the potential risks of drug-drug interactions and serotonin toxicity (ST) between these agents.
OBJECTIVES
A critical evaluation of the scientific literature is necessary to delineate the risks of ST when combining psychedelics with available serotonergic pharmacotherapy options. This review article describes signs and symptoms of ST, characterizes mechanisms of ST risk, summarizes what is known about serotonergic psychedelic drug interactions, and outlines potential management strategies.
RESULTS
True ST typically occurs with a serotonergic drug overdose or in combinations in which a drug that can increase intrasynaptic serotonin is combined with a monoamine oxidase inhibitor (MAOI). Serotonergic psychotropics that do not contain MAOIs are low risk in combination with psychedelics that also do not contain MAOIs. Signs and symptoms warranting immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or comatose mental state, muscle rigidity, pronounced hyperthermia (fever), and/or seizure activity.
CONCLUSIONS
Serotonin-related adverse reactions exist along a spectrum with serotonin syndrome being the most severe manifestations of ST. Due to varying serotonergic mechanisms of psychedelics and psychotropics, with varying propensities to increase intrasynaptic serotonin, some combinations may present a significant risk for serotonin toxicity (ST) while others are likely benign.
Topics: Hallucinogens; Humans; Monoamine Oxidase Inhibitors; Serotonin; Serotonin Agents; Selective Serotonin Reuptake Inhibitors
PubMed: 34251464
DOI: 10.1007/s00213-021-05876-x -
Cureus Dec 2020Stiff-person syndrome (SPS) is a rare and disabling central nervous system disorder with no satisfactory treatment. Muscle rigidity, sporadic muscle spasms, and chronic... (Review)
Review
Stiff-person syndrome (SPS) is a rare and disabling central nervous system disorder with no satisfactory treatment. Muscle rigidity, sporadic muscle spasms, and chronic muscle pain characterize SPS. SPS is strongly correlated with autoimmune diseases, and it is usual to find high titers of antibodies against acid decarboxylase (GAD65). Due to its highly disabling nature and complicated treatment, we aim to create a treatment protocol through a narrative review of currently available treatments that show efficacy. We expect to facilitate management based on treatment responses ranging from first-line medication to refractory medication. We conducted a medical subject heading (MeSH) strategy. We used the term SPS with the subheading treatment: "Stiff-Person Syndrome/Therapy" [MeSH]. An initial data gathering of 270 papers came out with the initial research. After using the inclusion criteria, we had 159 articles. We excluded 31 papers for being either systematic reviews, literature reviews, or meta-analysis. From the 128 remaining articles, we excluded another 104 papers because the extraction of the data was not possible or the study outcome did not meet our demands. There are two main treatments for SPS: GABAergic (gamma-aminobutyric acid) therapy and immunotherapy. For treatment, we suggest starting with benzodiazepines as first-line treatment. We recommend adding levetiracetam or pregabalin if symptoms persist. As second-line therapy, we recommend oral baclofen over rituximab and tacrolimus. We also suggest rituximab over tacrolimus. For patients with refractory treatment, we can use intrathecal baclofen, intravenous immunoglobulin (IVIG), or plasmapheresis. We conclude that intrathecal baclofen and IVIG are more effective than plasmapheresis in patients with refractory symptoms. Propofol may be used as a bridge - temporary therapy before initiating a permanent treatment.
PubMed: 33437550
DOI: 10.7759/cureus.11995 -
Current Neuropharmacology 2015Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening side-effect that can occur in response to treatment with antipsychotic drugs. Symptoms... (Review)
Review
Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening side-effect that can occur in response to treatment with antipsychotic drugs. Symptoms commonly include hyperpyrexia, muscle rigidity, autonomic dysfunction and altered mental status. In the current review we provide an overview on past and current developments in understanding the causes and treatment of NMS. Studies on the epidemiological incidence of NMS are evaluated, and we provide new data from the Canada Vigilance Adverse Reaction Online database to elaborate on drug-specific and antipsychotic drug polypharmacy instances of NMS reported between 1965 and 2012. Established risk factors are summarized with an emphasis on pharmacological and environmental causes. Leading theories about the etiopathology of NMS are discussed, including the potential contribution of the impact of dopamine receptor blockade and musculoskeletal fiber toxicity. A clinical perspective is provided whereby the clinical presentation and phenomenology of NMS is detailed, while the diagnosis of NMS and its differential is expounded. Current therapeutic strategies are outlined and the role for both pharmacological and non-pharmacological treatment strategies in alleviating the symptoms of NMS are discussed.
Topics: Animals; Antipsychotic Agents; Diagnosis, Differential; Humans; Incidence; Muscle Rigidity; Neuroleptic Malignant Syndrome; Risk Factors
PubMed: 26411967
DOI: 10.2174/1570159x13999150424113345