Intramuscular ophthalmic homatropine vs. atropine to prevent lethality in rates with dichlorvos poisoning

Abstract

Introduction: Most hospitals lack a sufficient supply of atropine to treat, simultaneously, patients poisoned with multiple organophosphorous compound (OC) or nerve agent. The presence of a ubiquitous alternate antidote would prove useful if mass poisoning occurred. Our objective was to evaluate the effect of ophthalmic homatropine (Isopto Homatropine 5%) on survivability in a rat model of significant, acute OC poisoning.Methods: Sprague-Dawley rats were randomized to one of five pre-treatment groups (N = 10 per group). Prior to experimentation, animals were pre-treated with intramuscular (IM) injections of either atropine 5 mg/kg, atropine 10 mg/kg, homatropine 10 mg/kg, or homatropine 20 mg/kg. The control group received 0.3 mL normal saline IM. Five minutes later, 25 mg/kg of dichlorvos was subcutaneously administered. Mortality rates were compared using Fisher's Exact test. Kaplan-Meier survival curves with Logrank analysis was also performed. If alive at 120 minutes, survival was assumed, and the study was terminated.Results: All rats pre-treated with normal saline, atropine 5 mg/kg, and homatropine 10 mg/kg died. Survival in the homatropine (20 mg/kg) and atropine (10 mg/kg) groups was 30% and 40% respectively. Times to death ranged between 4 and 12 minutes. Overall comparison of time to death revealed a statistically significant improvement for groups pre-treated with homatropine (20 mg/kg) and atropine (10 mg/kg).Conclusions: Pre-treatment with homatropine (20 mg/kg) was comparable with atropine (10 mg/kg) in preventing lethality in this rat model of acute OC poisoning.

Metoclopramide protection of diazinon-induced toxicosis in chickens

“…The cardinal treatment for organophosphate poisoning includes atropine to counteract the muscarinic signs and symptoms, and oximes to reactivate the inhibited cholinesterases [ 4 , 16 , 26 , 28 ]. However, the clinical results of administering antidotal therapy for organophosphate poisoning are far from perfect [ 4 , 6 , 16 , 26 , 28 ], and there are many ongoing experimental trials using other therapeutic and protective agents for controlling the signs and symptoms of poisoning, and especially those related to the nicotinic effects that are not controlled by atropine. Examples of such trials include antihistamine diphenhydramine [ 5 , 12 ], alpha-2-adrenoceptor agonists [ 7 , 29 ] and metoclopramide, which is a dopamine D2 receptor antagonist [ 14 , 22 - 24 ].…”

Pretreating Rats with Parenteral Ophthalmic Antimuscarinic Agents Decreases Mortality from Lethal Organophosphate Poisoning

“…12 In choosing a dose of homatropine for study, we found that doubling the dose of homatropine (20 mg/kg vs. 10 mg/kg of atropine sulfate) was equivalent to standard atropine sulfate in preventing death in our previous work in the laboratory as well as in this current experiment. 8 Our study revealed a significant survival benefit for rats treated with standard atropine sulfate (10 mg/kg), ophthalmic homatropine (20 mg/kg), and ophthalmic atropine sulfate (10 mg/kg). All subjects consistently exhibited fasciculations within 2-3 minutes of dichlorvos administration.…”

“…8 Before ophthalmic antidote testing, 30 animals were used to obtain an appropriate dose response. It was discovered that administration of dichlorvos (Pestanal; Sigma-Aldrich) subcutaneously (SC; 10 mg/kg) resulted in death within 7 minutes in 10 rats.…”

Pretreating Rats with Parenteral Ophthalmic Antimuscarinic Agents Decreases Mortality from Lethal Organophosphate Poisoning

“…Our previous work determined that reported LD50 values for dichlorvos and atropine dosing that were used in published studies were not adequate in our laboratory and thus necessitated a dose response phase before experimentation. 8 Before ophthalmic antidote testing, 30 animals were used to obtain an appropriate dose response. It was discovered that administration of dichlorvos (Pestanal; Sigma-Aldrich) subcutaneously (SC; 10 mg/kg) resulted in death within 7 minutes in 10 rats.…”