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1.
Am J Case Rep ; 23: e936217, 2022 May 06.
Article in English | MEDLINE | ID: covidwho-1835852

ABSTRACT

BACKGROUND Considering the ongoing coronavirus disease 2019 (COVID-19) pandemic, sufficient information about common and serious adverse events is needed to rapidly distribute COVID-19 vaccines worldwide. We report a case of neuroleptic malignant syndrome (NMS) with adrenal insufficiency after initial vaccination with Pfizer/BioNTech BNT162b2. CASE REPORT A 48-year-old man presented to the Emergency Department with fever and an altered mental status 7 days after receiving the first dose of the BNT162b2 COVID-19 vaccine. The patient had a history of end-stage renal disease and epilepsy treated with valproate. He was diagnosed with NMS based on the clinical findings of hyperthermia, muscular rigidity, and an elevated creatine kinase level. Additionally, a reduction in the response of cortisol to adrenocorticotropic hormone (ACTH) stimulation was observed in the rapid ACTH stimulation test. The patient was treated with dantrolene, bromocriptine, and hydrocortisone, and he responded well to treatment. Dantrolene and bromocriptine were tapered off over 4 weeks. Hydrocortisone was also tapered, and the patient was discharged on oral hydrocortisone (30 mg). CONCLUSIONS The present case suggests a possible link between the BNT162b2 COVID-19 vaccine and NMS with adrenal insufficiency based on the temporal relationship between vaccine administration and disease onset, although the patient was taking valproate, a potential cause of NMS. Having a high level of suspicion is important because the diagnosis of NMS with adrenal insufficiency is often challenging due to non-specific clinical manifestations. However, this case does not negate the utility of vaccination because these complications are extremely rare and can be treated with early diagnosis and proper management.


Subject(s)
Adrenal Insufficiency , BNT162 Vaccine , COVID-19 , Neuroleptic Malignant Syndrome , Adrenal Insufficiency/chemically induced , Adrenal Insufficiency/complications , Adrenocorticotropic Hormone , BNT162 Vaccine/adverse effects , Bromocriptine/therapeutic use , COVID-19/prevention & control , Dantrolene/therapeutic use , Humans , Hydrocortisone/therapeutic use , Male , Middle Aged , Neuroleptic Malignant Syndrome/diagnosis , Neuroleptic Malignant Syndrome/etiology , Neuroleptic Malignant Syndrome/therapy , Vaccination/adverse effects , Valproic Acid/adverse effects
3.
Eur Rev Med Pharmacol Sci ; 25(7): 3136-3144, 2021 04.
Article in English | MEDLINE | ID: covidwho-1194855

ABSTRACT

OBJECTIVE: Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of systemic inflammatory response syndrome (SIRS) and associated multiple organ dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic shock patients. This review summarized the potential mechanisms of therapeutic effects of dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided suggestions and strategies for future clinical studies.


Subject(s)
COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Dantrolene/therapeutic use , Sepsis/drug therapy , COVID-19/metabolism , Calcium/metabolism , Drug Repositioning , Endoplasmic Reticulum/metabolism , Humans , Mortality , Multiple Organ Failure , Ryanodine Receptor Calcium Release Channel/metabolism , SARS-CoV-2 , Sarcoplasmic Reticulum/metabolism , Sepsis/metabolism , Shock, Septic/drug therapy , Shock, Septic/metabolism
4.
Eur J Med Res ; 26(1): 18, 2021 Feb 08.
Article in English | MEDLINE | ID: covidwho-1069594

ABSTRACT

BACKGROUND: Patients with severe COVID-19 have disorders of the respiratory, cardiovascular, coagulation, skeletal muscle, and central nervous systems. These systemic failures may be associated with cytokine release syndrome, characterized by hyperpyrexia, thrombocytopenia, hyperferritinemia, and the elevation of other inflammatory markers. Rhabdomyolysis with high fever is a complication that is rarely found in COVID-19. The exact relations of these clinical conditions in patients with COVID-19 remain unknown. CASE PRESENTATION: We present the case of a 36-year-old man with severe COVID-19 complicated by rhabdomyolysis and high fever. After admission, his condition continued to deteriorate, with a high body temperature. On day 9, the patient had elevated creatine kinase and myoglobin levels consistent with rhabdomyolysis (26,046 U/L and 3668 ng/mL, respectively). In addition to viral therapy, he was immediately treated with hydration. However, the patient had persistent fever and elevated creatine kinase levels. The patient was diagnosed with malignant hyperthermia as a late complication of COVID-19, although he had no hereditary predisposition to malignant hyperthermia or neuroleptic malignant syndrome. The administration of dantrolene with muscle relaxation and anti-inflammatory function showed potential efficacy for rhabdomyolysis, high fever, and increased plasma inflammatory markers. CONCLUSIONS: Malignant hyperthermia is triggered by not only anesthetic agents but also viral infections. A possible mechanism of malignant hyperthermia is hypersensitivity of calcium release from the sarcoplasmic reticulum. These include mutations in or the activation of the skeletal muscle ryanodine receptor calcium release channel. Dantrolene is a ryanodine receptor antagonist and is used as an anti-inflammatory agent. The administration of dantrolene showed potential efficacy for rhabdomyolysis, high body temperature due to inflammation, and increased inflammatory markers. The underlying mechanism of the association of rhabdomyolysis and high fever in COVID-19 might be similar to the pathogenesis of malignant hyperthermia.


Subject(s)
COVID-19/complications , Dantrolene/therapeutic use , Muscle Relaxants, Central/therapeutic use , Rhabdomyolysis/drug therapy , Rhabdomyolysis/virology , Adult , Humans , Male , Malignant Hyperthermia/complications , Malignant Hyperthermia/virology , SARS-CoV-2
5.
Eur Rev Med Pharmacol Sci ; 24(19): 10228-10238, 2020 10.
Article in English | MEDLINE | ID: covidwho-890958

ABSTRACT

Dantrolene, an FDA approved drug to treat malignant hyperthermia and muscle spasm, has been demonstrated to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediated toxicity of host cells. Ryanodine receptor overactivation and associated disruption of intracellular Ca2+ homeostasis play important roles in SARS-CoV-2 infection and replication of host cells. Dantrolene, as an inhibitor of RyRs, is expected to ameliorate these detrimental effects of SARS-CoV-2 in host cells. Additionally, dantrolene has also been shown to inhibit multiple cell or organ damage induced by hypoxia/ischemia, mitochondria damage, oxidative stresses, inflammation, impairment of autophagy and apoptosis, etc., which are often the causes of severity and mortality of COVID-19 patients. We have repurposed that dantrolene has a high potential at treating COVID-19 patients and reducing its morbidity and mortality.


Subject(s)
COVID-19/drug therapy , COVID-19/metabolism , Calcium/metabolism , Dantrolene/therapeutic use , Drug Repositioning , Homeostasis/drug effects , Humans , Muscle Relaxants, Central/therapeutic use , Pandemics
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