Analgesics

Bateman, D Nicholas; Jefferson, Robert D; Thomas, Simon; Thompson, John P.; Vale, J Allister

doi:10.1093/med/9780199594740.003.0005

Cited by 2 publications

(4 citation statements)

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“…Two of the major challenges in the medical treatment of nerve agent poisoning are the prevention of death and a reduction in nerve agent induced brain pathologies. In the case of soman exposure, these challenges are especially difficult to overcome because of soman's ability to rapidly age (1-3 minutes) and irreversibly bind AChE (Romano, 2007, Bateman, 2014. Once this aging process has occurred, reactivation of CWNA-inhibited AChE through oxime therapy is no longer effective.…”

Section: Discussionmentioning

confidence: 99%

“…Nerve agent countermeasures emphasize the reduction of post-exposure brain pathologies and prevention of death. This is especially difficult with soman exposure because it permanently and irreversibly inhibits AChE within minutes after intoxication (a result of rapid aging) (Romano, 2007, Bateman, 2014. Pharmacological control of nerve agent-induced seizures is critical for survival following nerve agent exposure (Shih et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Anticonvulsant efficacy of antihistamine cyproheptadine in rats exposed to the chemical warfare nerve agent soman

2017

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Organophosphate compounds, such as soman and sarin, are highly toxic chemical warfare nerve agents that cause a build-up of acetylcholine in synapses and neuromuscular junctions. Current therapies aim to prevent seizures and protect against brain injury following exposure. The present study was designed to evaluate the effectiveness of the antihistamine cyproheptadine in improving survival and controlling seizures in rats exposed to soman. Rats were pretreated with the oxime reactivator HI-6 (125mg/kg, ip) 30min prior to soman exposure (225μg/kg, sc) and then treated with atropine methylnitrate (AMN, 2.0mg/kg, im) 1min after soman. Cyproheptadine (10, 13, 16 or 20mg/kg, ip) was given at one of three time points: 1min after soman intoxication, at the onset of soman-induced seizures or 5min after seizure onset. Control animals were exposed to soman and given an equivalent volume of sterile water instead of cyproheptadine. The incidence of seizures, mortality, neuron counts, neuropathology and apoptosis in specific regions of the brain were evaluated. In animals given HI-6 and AMN the incidence of soman-induced seizure and mortality rate within the first 24h were 100%. When cyproheptadine was given at a dose of 13 or 20mg/kg 1min after soman exposure, the incidence of seizures was reduced from 100% to 13% and 30%, respectively. In addition, cyproheptadine given at 1min after soman exposure increased the survival rate to 100% regardless of dose. When cyproheptadine was administered at seizure onset, seizures were terminated in 100% of the animals at doses above 10mg/kg. The survival rate with cyproheptadine treatment at the onset of seizure was ≥83%. Seizures terminated in ≥75% of the animals that received cyproheptadine 5min after soman-induced seizure onset. When given at 5min after seizure onset the survival rate was 100% at all tested doses of cyproheptadine. The neuropathology scores and the number of TUNEL positive cells in the brain regions examined decreased at all time points and cyproheptadine doses tested. These observations indicate that cyproheptadine treatment can effectively control seizures, improve survival, reduce seizure duration and reduce the number of dying cells in the brain following soman exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anticonvulsant efficacy of antihistamine cyproheptadine in rats exposed to the chemical warfare nerve agent soman

2017

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“…Other complications in severe poisoning include lactic acidosis, hyperthermia, and rhabdomyolysis. [ 3 ] In adults, 1–2 mg/kg is considered the lethal dose,[ 5 ] however, poisoning with doses as low as 20 mg were lethal and as high as 3750 mg have been salvaged. [ 6 ] The cardiovascular effects due to strychnine are usually tachycardia, hypertension, and feeble pulse.…”

Section: Discussionmentioning

confidence: 99%

“…[ 7 ] However, rarely bradycardia and hypotension have also been reported. [ 5 ] Other causes of bradycardia in strychnine poisoning that manifest with ECG changes are nonspecific ST-segment and T-wave changes and QRS and QTc prolongation secondary to hypocalcemia. [ 5 ] Hypokalemia has also been reported with strychnine poisoning[ 5 ] which may contribute to bradycardia.…”

Section: Discussionmentioning

confidence: 99%