Antidote for potassium toxicity9/18/2023 ![]() The aim of that study was to find a safe dose of FDP that might be used to reverse cardio-toxicity. We conducted a small phase II study of increasing IV bolus doses (30 to 250mg/kg) of FDP in patients with yellow oleander poisoning in Sri Lanka in 2006-7. There was also no rise in serum potassium in the group receiving FDP while marked hyperkalemia occurred in the control group. Cardiac arrhythmias in dogs (6/6 100%) treated with FDP (50mg/kg IV) reverted back to sinus rhythm within 30 minutes while the arrhythmias in the control animals killed one animal and did not revert over four hours in the other five at which time they were sacrificed. This study showed evidence of effectiveness of FDP in dogs poisoned with a relative of the yellow oleander - the common or pink oleander. These theoretical benefits of FDP have been shown in an animal study done at the Mississippi School of Medicine, USA. A decrease in ionised serum calcium and/or cardiac uptake of calcium may also be favourable, given the high intracellular calcium that occurs in cardiac glycoside poisoning. It is hypothesised that these mechanisms may contribute to its activity in cardiac glycoside poisoning where Na-K-ATPase is inhibited and extracellular potassium is high. The relative production of ATP is greater for FDP than glucose.įDP has also been shown to stimulate Na-K-ATPase activity, and inhibit potassium efflux from myocardial cells. This can increase ATP production in circumstances where phosphofructokinase is inhibited (for example by lactate). Given intravenously, FDP is capable of being actively transported into cells and acting as an alternative energy source to glucose. Phosphofructokinase activity is the main rate-limiting factor for ATP production from glucose under anaerobic conditions. It is produced from glucose by the action of phosphofructokinase during glycolysis and is in turn broken down into pyruvate. This in turn will further reduce the activity of Na-K-ATPase resulting in a vicious cycle.įDP (CAS registry number 488-69-7 Merck monograph number 4297) is a phosphorylated sugar that is a normal physiological intermediary in glycolysis. Hypotension interferes with intracellular production of ATP through glycolysis, as lactate (produced due to anaerobic metabolism) inhibits the rate limiting enzyme phosphofructokinase. Patients may develop arrhythmias and become hypotensive. Patients also develop very high serum potassium concentrations as a result of inhibition of Na-K-ATPase. These effects lead to increased automaticity and excitability both during early and late depolarization of the cardiac cell. This rise in intracellular calcium may be a mechanism for ventricular arrhythmias. ![]() Cardiac glycosides inhibit the enzyme Na-K-ATPase of the cardiac myocyte and the conducting system and increase intracellular calcium concentrations. At present, symptomatic cardiac glycoside poisoning carries a mortality rate of 10% in Sri Lanka. ![]() Trial RegistrationĬardiac glycoside toxicity is the most common type of plant poisoning in Sri Lanka and some other South Asian countries. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. ![]() Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. ![]()
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