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Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection.

ABSTRACT: Currently available cyanide antidotes must be given by intravenous injection over 5-10 min, making them ill-suited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramuscular injection. Here we show that adding sodium nitrite to cobinamide yields a stable derivative (referred to as nitrocobinamide) that rescues cyanide-poisoned mice and rabbits when given by intramuscular injection. We also show that the efficacy of nitrocobinamide is markedly enhanced by coadministering sodium thiosulfate (reducing the total injected volume), and we calculate that ?1.4 mL each of nitrocobinamide and sodium thiosulfate should rescue a human from a lethal cyanide exposure.

SUBMITTER: Chan A

PROVIDER: S-EPMC4494098 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection.

Chan Adriano A Jiang Jingjing J Fridman Alla A Guo Ling T LT Shelton G Diane GD Liu Ming-Tao MT Green Carol C Haushalter Kristofer J KJ Patel Hemal H HH Lee Jangwoen J Yoon David D Burney Tanya T Mukai David D Mahon Sari B SB Brenner Matthew M Pilz Renate B RB Boss Gerry R GR

Journal of medicinal chemistry 20150216 4

Currently available cyanide antidotes must be given by intravenous injection over 5-10 min, making them ill-suited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramus ...[more]

PMID: 25650735

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Project description:AimTo review the effect of different intramuscular injection (IMI) techniques on injection associated pain, in adults.MethodsThe review protocol was registered on PROSPERO (CRD42019136097). MEDLINE, EMBASE, British Nursing Index and CINAHL were searched up to June 2020. Included studies were appraised and a meta-analysis, where appropriate, was conducted with a random effects model and test for heterogeneity. Standardised mean difference (SMD) with a 95% confidence interval in reported injection pain (intervention cf. control) was reported.Results29 studies were included in the systematic review and 20 studies in the meta-analysis. 13 IMI techniques were identified. 10 studies applied local pressure to the injection site. Of these, applying manual pressure (4 studies, SMD = -0.85[-1.36,-0.33]) and Helfer (rhythmic) tapping (3 studies, SMD = -2.95[-5.51,-0.39]) to the injection site reduced injection pain, whereas the use of a plastic device to apply local pressure to the skin (ShotBlocker) did not significantly reduce pain (2 studies, SMD = -0.51[-1.58,0.56]). Acupressure techniques which mostly involved applying sustained pressure followed by intermittent pressure (tapping) to acupressure points local to the injection site reduced pain (4 studies: SMD = -1.62[-2.80,-0.44]), as did injections to the ventrogluteal site compared to the dorsogluteal site (2 studies, SMD = -0.43[-0.81,-0.06]). There was insufficient evidence on the benefits of the 'Z track technique' (2 studies, SMD = -0.20[-0.41,0.01]) and the cold needle technique (2 studies, SMD = -0.73[-1.83,0.37]) on injection pain. The effect of changing the needle after drawing up the injectate on injection pain was conflicting and warming the injectate did not reduce pain. Limitations included considerable heterogeneity, poor reporting of randomisation, and possible bias in outcome measures from unblinding of assessors or participants.ConclusionsManual pressure or rhythmic tapping over the injection site and applying local pressure around the injection site reduced IMI pain. However, there was very high unexplained heterogeneity between studies and risk of significant bias within small studies.

Dataset Information

Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection.

Publications

Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection.

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