Ricin intravenous

Drugs Available (No specific anti-toxin) Active immunization and passive antibody prophylaxis are under study, as both are effective in protecting animals from death following exposure by intravenous or respiratory routes. Ricin is not dermally active therefore, respiratory protection is the most critical means of prevention. 

Candidate vaccines under development are immunogenic and confer protection against lethal aerosol exposures. Recent animal studies have shown that either active immunization or passive prophylaxis may be effective against intravenous or intraperitoneal intoxication with ricin (Poh et al, 1994). In the case of inhalational exposure, active immunization or prophylactic administration of aerosolized specific anti-ricin antibody may also be effective (Poli et al, 1994). Unfortunately, these applications may not be clinically available since they are still under investigation. 

Intravenous fluids are very important to maintain normovolemia and urine output. If hematuria is present, consider alkalinization of the urine. A goat anti-ricin polyclonal and a mouse anti-ricin A-chain monoclonal antibody have been tested and shown to neutralize ricin in castor bean extract, but they are not clinically available (Lemley and Wright, 1991 Wannemacher et al, 1991). 

Possible routes of exposure include cutaneous, mucosal, gastrointestinal, inhalation, and parenteral (intravenous or intramuscular). Gastrointestinal exposures are usually accidental and occur most commonly when castor (ricin) or jequirty (abrin) beans are chewed or swallowed. Cutaneous exposures are limited primarily to castor beans, which are unusually allergenic and may cause severe cutaneous hypersensitivity and systemic allergic reactions. Inhalation and parenteral exposures are generally limited to intentional, usually malicious, exposures. 

Ricin s potent immogenicity raises hope for development of an effective vaccine (36). Animal studies reveal that either active or passive immunization may be effective for intravenous or intraperitoneal exposures but only if given within a few... 

Many of the features observed in poisoning can be explained by ricin-induced endothelial cell damage, with fluid and protein leakage and tissue oedema, causing a so-called vascular leak syndrome . Disseminated intravascular coagulation has been observed in experimental animals following intravenous ricin administration and this is also likely to reflect endothelial cell damage. 

When intravenous ricin 18-20 pg/m2 (approximately 0.5 pg/kg body weight) was investigated... 

Symptomatic and supportive measures are the mainstay of management of this highly toxic route of exposure. There is some evidence that the intravenous administration of anti-ricin antibody shortly (within 1-2 h) after ricin exposure may improve survival (Houston, 1982) although this has to be confirmed and probably has no utility in a civilian population where there would be no near real-time detection of ricin exposure. 

The toxicity of ricin is increased several 100-fold when administered parenterally (not via the gut). Fatal levels in rats given ricin hy intravenous injection have been shown to he as low as 0.3 pg/kg body weight (about 60 ng/animal), with mice being less sensitive (LDgg 2.7 pg/kg). Weight for weight, ricin is twice as poisonous as cobra venom. 

Treatment of a person poisoned by ricin involves alimentary canal decontamination procedures so as to prevent absorption of the toxin. These include the use of syrup of ipecac to induce vomiting, activated charcoal to adsorb the toxin and cathartics to accelerate expulsion. Where a suspected poisoning has occurred but the patient remains asymptomatic, alimentary canal decontamination should still be undertaken and hospital observation for at least six hours after suspected poisoning should take place. The patient should be told to return immediately if symptoms begin. Where more severe poisoning has occurred treatment with intravenous fluids, monitoring for haemolysis and hypoglycaemia, supportive care and the possibility of hypovolaemia should be considered. 

In one large clinical trial,40 low doses (18-20 pg/ m2) of intravenous ricin administered to cancer patients were well tolerated. Flulike symptoms with fatigue—in some cases very pronounced fatigue— and muscular pain were common, and sometimes nausea and vomiting occurred. The symptoms began 4 to 6 hours after administration and lasted for 1 to 2 days. Two toxic deaths were reported in Phase I clinical trails of the closely related protein toxin, abrin these patients had general seizures and other signs of central nervous system toxicity. 

Enzyme-linked immunosorbent assays (for blood or other body fluids)50 or immunohistochemical techniques (for direct analysis of tissues) may be useful in confirming ricin intoxication. However, because ricin is bound very quickly regardless of route of challenge, and metabolized before excretion, identification in body fluids or tissues is difficult. In rats exposed to ricin labeled with iodine 125 by intravenous injection, the radioactive label was found in liver (46%), muscle (13%), and spleen (9%) 30 minutes after intravenous injection.51 Ricin was quickly cleared from the animals, with only 11% remaining after 24 hours 70% was excreted in the urine as low-molecular-weight metabolites. Attempts at identification of the toxin may also include introduction of biological autopsy materials into mice or cultured cells and neutralization through the use of specific antibodies. 

As is the case in toxicity and pathogenesis of intoxication, the route of exposure is important in relation to possible modes and their likelihood of success of prophylaxis and therapy. For oral intoxication, supportive therapy includes activated charcoal administration and intravenous fluid and electrolyte replacement. For inhalational intoxication, supportive therapy to counteract acute pulmonary edema and respiratory distress is indicated. Symptomatic care is the only intervention presently available to clinicians for the treatment of incapacitating or lethal doses of inhaled ricin. Positive end-expiratory ventilatory therapy, fluid and electrolyte replacement, antiinflammatory agents, and analgesics... 

No antidote exists for ricin. Ricin poisoning is treated by giving the victim supportive medical care to minimize the effects of the poisoning. The types of supportive medical care would depend on several factors, such as the route by which the victim was poisoned (that is, by inhalation, ingestion, or injection). Care could include such measures as helping the victim breathe and giving him or her intravenous fluids and medications to treat swelling. 

The ability of PAAs to mediate the delivery of proteic macromolecules such as toxins has been investigated. With gelonin and ricin A-chain as payloads, it was shown that these polymers are able to permeabilize the endosomal membrane, and thus aid cytoplasmic entry, displaying good results in both in vitro and in vivo delivery. In particular, PAAs were able to restore toxin cytotoxicity, whereas neutral polymers such as dextran were unable to mediate this effect. Moreover, PAAs were able to escape the reticuloendothelial system (clearance after intravenous administration), allowing tumor targeting by the enhanced permeability and retention... 

Ricin in the liver first targets the Kupffer cells which are heavily damaged as early as 4 h after the intravenous inoculation of 6 LDioo into mice (Bingen et al. 1987). Four hours after the inoculation of ricin every Kupffer cell bore several worm-Hke structures, which sometimes took a spindle-like aspect. About 14 % of the completely lysed cells (29 of 208) lay on the endothehal fining within the sinusoid. In vivo, Kupffer cells accumulated I-labelled ricin to a much greater extent than parenchymal cells (Skilleter et al. 1981). 

Many of the results for ricin injection derive from rodent studies. The highest concentration of ricin was foimd to localize to the spleen after either intravenous or intraperitoneal administration of I-ricin, whereas... 

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