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10.1111/bph.15101 http://scihub22266oqcxt.onion/10.1111/bph.15101 32415690!7572456!32415690     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Pharmacol 2020 ; 177 (21): 4975-4989 Nephropedia Template TP {{tp|p=32415690|t=2020. Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam |pdf=|usr=}}{{32415690}} gab.com Text Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=32415690 #FOAvip BACKGROUND AND PURPOSE: Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity. EXPERIMENTAL APPROACH: In vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine alone or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone-anaesthetised rats and rabbits. Randomised, controlled treatment studies in rats assessed diazepam, clonazepam and Ro5-4864 administered: (i) prior, (ii) during and (iii) after chloroquine and the effects of diazepam: (iv) at high dose, (v) in urethane-anaesthetised rats and (vi) co-administered with adrenaline. KEY RESULTS: Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose-dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between treatments and control. Diazepam increased heart rate in study (iv) and as with clonazepam also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia. CONCLUSION AND IMPLICATIONS: Neither diazepam nor other ligands for benzodiazepine binding sites protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc. Twit Text FOAVip Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=32415690 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32415690 #FOAvip English Wikipedia <ref>{{Cite pmid|32415690}}</ref> Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam #MMPMID32415690 Hughes DA Br J Pharmacol 2020[Nov]; 177 (21): 4975-4989 PMID32415690show ga BACKGROUND AND PURPOSE: Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity. EXPERIMENTAL APPROACH: In vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine alone or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone-anaesthetised rats and rabbits. Randomised, controlled treatment studies in rats assessed diazepam, clonazepam and Ro5-4864 administered: (i) prior, (ii) during and (iii) after chloroquine and the effects of diazepam: (iv) at high dose, (v) in urethane-anaesthetised rats and (vi) co-administered with adrenaline. KEY RESULTS: Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose-dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between treatments and control. Diazepam increased heart rate in study (iv) and as with clonazepam also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia. CONCLUSION AND IMPLICATIONS: Neither diazepam nor other ligands for benzodiazepine binding sites protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc. |Animals[MESH] |Arrhythmias, Cardiac/*chemically induced/prevention & control[MESH] |Benzodiazepinones/pharmacology[MESH] |COVID-19[MESH] |Cardiotoxicity/*etiology/prevention & control[MESH] |Chloroquine/*poisoning[MESH] |Clonazepam/pharmacology[MESH] |Coronavirus Infections/drug therapy[MESH] |Diazepam/administration & dosage/*pharmacology[MESH] |Dose-Response Relationship, Drug[MESH] |Drug Overdose[MESH] |Electrocardiography[MESH] |Female[MESH] |Hypokalemia/chemically induced[MESH] |Male[MESH] |Pandemics[MESH] |Pneumonia, Viral/drug therapy[MESH] |Rabbits[MESH] |Random Allocation[MESH] |Rats[MESH]Acute chloroquine poisoning: A comprehensive experimental toxicology a(epmc).pdf DeepDyve Pubget Overpricing