Emergency drugs
Daniel Cottle, Shondipon Laha, Peter Nightingale in Anaesthetics for Junior Doctors and Allied Professionals, 2018
Dantrolene is a drug used for malignant hyperthermia. It acts on the sarcoplasmic reticulum (inhibiting the ryanodine receptor) in skeletal muscle to reduce calcium ion release and thus decrease the damaging global muscle contractions. Vials contain dantrolene 20 mg plus mannitol 3 g and sodium hydroxide: it needs to be made up with 60 mL of sterile water.For malignant hyperthermia an initial dose of 1 mg/kg intravenously (approximately four vials) is given followed by repeated doses up to 10 mg/kg (average requirement is 2–3 mg/kg).This is difficult to dissolve and will require a large volume of sterile water and so is best made up in a large sterile theatre dish. It has a pH of 9.5 and causes tissue necrosis with extravasation.
Paper 3 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
Dantrolene is a phenyl hydantoin derivative, which is used in the management of malignant hyperthermia (MH) and in the prevention and treatment of muscle spasm in patients with spinal cord injury, tetanus and neuroleptic malignant syndrome. Dantrolene causes muscle relaxation by inhibition of the ryanodine receptor on the sarcoplasmic reticulum in skeletal muscle cells to reduce the accumulation of intracellular calcium ions. Dantrolene is prepared in an ampoule as a lyophilized orange powder containing 20 mg dantrolene sodium, 3 g mannitol (to increase solubility) and sodium bicarbonate. Each vial is reconstituted with 60 mL water, which can be labour intensive in an emergency. The usual initial dose in the management of malignant hyperthermia is a 2.5 mg·kg−1 bolus, followed by additional 1 mg·kg−1 boluses as required up to a maximum of 10 mg·kg−1. Dantrolene is not routinely used in the prophylaxis of MH in susceptible individuals due to the occurrence of side effects such as sedation, muscle weakness (especially respiratory), gastrointestinal upset and hepatic dysfunction.
Pleural disease induced by drugs
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Dantrolene is used as a skeletal muscle relaxant. Common adverse effects include nausea, gastrointestinal atony, hepatitis and sedation. Dantrolene-associated pleural effusions have been reported in six patients who received doses between 100 and 400 mg per day.20 The pleuropulmonary reaction typically presents with pleurodynia, fever and pleural effusion. Pleural effusion and pleural fibrosis are late sequelae with an onset 2 months to 12 years after initiation of the drug. The pleural effusion is typically unilateral, with pleural fluid eosinophilia being a prominent finding – ranging from 33 to 66 per cent of the total nucleated cell count. All effusions were exudates with normal glucose concentrations. Peripheral blood eosinophilia (7–18 per cent) is usually present. Parenchymal infiltrates have not been documented with dantrolene-induced pleural disease. Drug withdrawal is associated with a rapid decrease in symptoms and resolution of the pleural effusion.
Spasticity management and resolution of paroxysmal sympathetic hyperactivity in the acute care setting: a case series
Published in Brain Injury, 2022
Arline Edmond, Ondrea McKay, Natasha Mehta, Laurie Dabaghian, Peter Yonclas
Spasticity is a common occurrence following traumatic brain injury and when untreated can result in long-term morbidity for patients and their recovery. As part of our consultation of trauma patients, physiatrists will at times be asked to manage spasticity. First-line treatment is typically nonpharmacologic, but many patients tend to need additional medications or interventions to prevent contracture. Usually, first-line oral medications used for spasticity are baclofen, dantrolene, and gabapentin, which have secondarily been shown to also be effective in some cases of PSH (13,21). The GABA-ergic action of baclofen and gabapentin is thought to have some effect in the mechanism of PSH, but exact action is unknown. Dantrolene, which is often used to treat neuroleptic malignant syndrome, can be very helpful in cases of severe posturing during PSH as these two entities can clinically appear similar. If spasticity is a precipitating factor as we suggest, then focal spasticity management could offer a treatment option without the systemic side effects of oral medications.
Toxicoepidemiology and predictors of death in 2,4-dinitrophenol (DNP) toxicity
Published in Clinical Toxicology, 2021
A. J. Potts, N. J. Bowman, D. L. Seger, S. H. L. Thomas
There is no specific antidote for DNP poisoning [9,10] and no specific evidence to demonstrate the effectiveness of different approaches, so the management of DNP poisoning remains largely supportive. In the absence of contraindications, the use of oral activated charcoal should be considered if the patient presents soon after ingestion. Use of sedation (e.g., benzodiazepines) for aggressive control of agitation is rational as muscular activity increases heat generation. Cooling measures should be instituted early in those developing pyrexia, starting with simple non-invasive methods such as mist and fan techniques, external ice packs or other external cooling devices, progressing to invasive methods such as cold fluid lavage or intravascular cooling methods if temperature continues to increase. There is no rigorous evidence of efficacy for dantrolene in DNP poisoning and its role in management has been contested, [7] although successful use in those with extreme pyrexia has been reported [11]. Fluid loss may occur due to gastrointestinal disturbances or pyrexia and adequate replacement is important. This also requires careful monitoring of electrolytes to decrease the risk of hyperkalaemia. Intubation may be difficult in critically ill patients with advanced DNP toxicity as muscular spasms and jaw clenching can occur; early intubation and ventilation is therefore appropriate for the deteriorating patient with DNP toxicity.
Targeting pathological leak of ryanodine receptors: preclinical progress and the potential impact on treatments for cardiac arrhythmias and heart failure
Published in Expert Opinion on Therapeutic Targets, 2020
Patrick Connell, Tarah A. Word, Xander H. T. Wehrens
Dantrolene is a hydantoin derivative that is currently used clinically for the treatment of malignant hyperthermia (MH), a condition caused by pathological SR Ca2+ leak through ryanodine receptor isoform 1 (RyR1) in skeletal muscle [97]. Dantrolene’s mechanism of action involves CaM-dependent stabilization of the interaction between the N-terminus and central domains, which is defective in case of RyR1 channels with MH-associated mutations [97,98]. Dantrolene was also found to be effective in stabilizing CPVT-mutant RyR2 channels in a similar fashion [99]. Dantrolene decreased SR Ca2+ leak and inhibited Ca2+ sparks and DADs in cardiomyocytes isolated from failing dog hearts [99]. Similar results were obtained in ventricular myocytes isolated from rabbits with HF, in which dantrolene decreased Ca2+ sparks and increased SR Ca2+ stores, a sign of preserved intracellular inotropy [100]. Dantrolene was also found to significantly decrease epinephrine-induced VT and inhibited Ca2+ sparks and transients in a pressure overload-induced HF mouse model [101]. Dantrolene decreased the frequency of premature ventricular contractions at rest and eliminated exercise-induced VT while reducing epinephrine-induced VT in a mouse model of CPVT [97]. Dantrolene also normalized Ca2+ spark activity back to control-levels and eliminated DADs in iPSC-CMs from CPVT patients with RyR2 mutations [102].
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