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An acute massive epidemic of arsenic poisoning in Argentina involved 718 subjects. Urine samples were obtained from 307. The 49 with urine arsenic 76-500 micrograms/dl and 12 with urine arsenic greater than 500 micrograms/dL received dimercaprol treatment. Symptomatology increased with the urine arsenic with increased diarrhea, vomiting and systemic symptoms at urine arsenic greater than 75 micrograms/dL.
We present a case of ingestion of a commonly used stool fixative containing 675 mg of mercuric chloride per 15 mL vial. Early chelator therapy with dimercaprol and aggressive hydration were initiated and the patient remained asymptomatic. Safety packaging of this product is recommended.
CASE REPORT: An 86-year-old woman accidentally ingested a preparation containing zinc and copper sulfate. At ninety minutes after ingestion, the peak plasma concentration was 1979 micrograms/dL for zinc and 209 micrograms/dL for copper, suggesting preferential absorption of zinc. The major complications were gastric and bronchial inflammation due to the corrosive properties of these compounds. Systemic manifestations also developed with cardiovascular failure and renal insufficiency, but the patient made a complete recovery. In addition to symptomatic treatment, chelation therapy with dimercaprol and D-penicillamine was given for 48 h. CONCLUSION: The available clinical and toxicokinetic data do not support the benefits of chelation in addition to supportive therapy.
Pharmacological studies were performed on allithiamine (TAD), thiamine propyl disulfide (TPD), and thiamine tetrahydrofurfuryl disulfide (TTFD) to investigate positive inotropic and negative chronotropic effects seen when they are applied to spontaneous beats in isolated guinea pig atria at concentrations higher than 10-5 g/ml. 1. The effects of thiamine 8-(methyl-6-acetyldihydrothioacetate) disulfide (TATD) and thiamine hydroxyethyl disulfide (TOED) at 5 x 10-4 were slight, and those of dibenzoyl thiamine (DBT) and thiamine were limited at any concentration. 2. Dimethyl propyl disulfide (DMPD) which has anti-thiamine activity, showed these effects at concentrations higher than 10-5. 3. The negative chronotropic effect of TAD, TPD, and TTFD was not influenced by the prior application of atropine, and the positive inotropic effect was not influenced by propranolol. 4. The effects of TTFD on the electrically driven left atrial muscle were remarkable when the muscle was driven at low frequency, while they were less remarkable at high frequency. 5. The decrease in tension of the electrically driven left atria induced by mersalyl at 5 x 10-4 g/ml was recovered by the subsequent addition of TTFD or TPD at 5 x 10-4 as well as dimercaprol at 5 x 10-5. From the results, it was assumed that (a) the effects of TAD, TPD and TTFD might relate to their common chemical structure of the disulfide, especially to the alkyldisulfide chain, (b) the effects are irrevelant to their common activity as an vitamin B1 and to either cholinergic or adrenergic effect, and (c) a mutual dependence is seen between the positive inotropic effect and the negative chronotropic effect.
A loop ligated at both sides was made in the ilecoecal portion of rabbit intestine. As2O3 solution was infused into this loop and the blood circulating around this loop was collected from the cannulated vein. As2O3 content absorbed in blood as well as that remaining in this loop were determined. In control rabbits on no drugs, approx. 30% of As2O3 infused was absorbed into the blood in 60 minutes. However, in rabbits on parenteral dimercaprol (BAL) or thioctic acid (TA), the content of As2O3 absorbed into the blood decreased remarkably while the content of As2O3 remaining in the loop increased. On the other hand, even when BAL or TA were added directly into thip loop containing As2O3, the content of As2O3 absorbed in blood decreased markedly, compared with that of the control group. Thus it was demonstrated that BAL or TA combined with AsO3(3-) after being excreted into the intestinal tract from the bile-duct, bringing about inhibition of the enteral absorption of As2O3.
Neonatal mercury poisoning, especially that due to merbromin ingestion, is uncommon. We describe the case of a 10 day old newborn infant who was given mercurochrome orally for 7 days due to misunderstanding of medical instructions. Initial symptoms included loss of appetite and low weight increase. Elevated blood mercury concentrations were found. Chelating therapy with dimercaprol was initiated and the patient's evolution was good. We discuss the potential toxicity of mercury and emphasise the importance of the transmission of information by physicians, especially to the immigrant population.
Thirty-six h after intentionally ingesting 25 g of mercuric chloride powder mixed with 5O mL of milk, an elderly woman presented to the emergency department with diffuse upper gastrointestinal erosions and acute renal failure. The patient was treated with dimercaprol and hemodialysis, and was discharged from the hospital without clinically apparent sequelae. However, elevated serum concentrations of amylase and proteases persisted for several months despite normal findings by computed tomography including contrast administration. Delayed absorption and weakened corrosive effect may have resulted from the binding of mercuric chloride to thiol-containing proteins in milk, improving the clinical outcome.
Nowadays mercury poisoning usually results from the oral ingestion of methylmercury or from inhalation of mercury vapor. Mercury intoxication in a gold prospector after inhalation of mercury vapor is described. The patient presented a history of fever, tachypnea and headache. Despite the treatment with dimercaprol, penicillamine and intensive supportive care the patient died with symptoms of acute respiratory distress.
A 27 year old agricultural worker presented about one month after treating cereal seeds with an alcoxyalkyl mercurial derivative, an encephalopathy with a confusional state, a cerebellar stato-kinetic syndrome, an intention tremor and grand mal epileptic fits. Treatment with dimercaprol produced a clinical improvement on the fourth day with a fall in blood mercury from 3.5 mug to 2.2 mug whilst urinary excretion of mercury remained low. A fortnight later the patient was completely cured. Although less common than collective poisoning by ingestion, organo-mercurial encephalopathies due to occupational exposure are a real danger although it is not known whether the relative rareness of published cases is due only to lack of observance of security rules or to individual sensitivity which might be due to increased absorption of mercury through the lungs or skin. This case shows that although alkyl mercurial derivatives are reputed to be the most dangerous, alcoxyalkyl derivatives may also cause encephalopathies. Also, as long as non-toxic substances remain unavailable for use in agriculture, one should emphasise the necessity of careful observance of the security rules during manipulation of these products.
Hyperthermic effect of arsenic was investigated in rabbits. Injections of arsenic trioxide (0.0001 to 0.1 micrograms) into a lateral cerebral ventricle of the rabbit evoked a dose-dependent hyperthermia, respiratory stimulation and peripheral vasodilatation. Heat loss through respiratory stimulation and peripheral vasodilatation appeared responsible for the long latent period and the slight hypothermia sometimes obtained during this period as these effects followed the same time course. These effects were centrally mediated as demonstrated by the lack of efficacy of the same doses by the intravenous route. The hyperthermic effect of arsenic was antagonized by the sulphydryl donator, dimercaprol, the a-adrenoceptor blocking agent-phenoxybenzamine and the PG-synthesis inhibitor-aspirin. Multiple sites, for antagonistic effects of these substances can be explained by the action of arsenic in inactivating sulphydryl containing enzymes which are many and catalyze diverse biochemical reactions.
Oxygen-derived free radicals and their metabolites may contribute to the extension of cellular injury that occurs on reperfusion of the ischemic myocardium; and therapy directed against the toxic effects of reactive oxygen species has provided protection to the ischemic myocardium which undergoes subsequent reperfusion. We evaluated the effectiveness of dimercapto-propanol (1,2-dimercapto-propanol, British Anti-Lewisite, dimercaprol) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Dimercaptopropanol is a thiol agent, with two free sulfhydryl groups per molecule, which has no effect on glutathione status nor on the total tissue thiol pool. Pretreatment of the hearts with 10(-6) M dimercapto-propanol resulted in marked myocardial protection, measured in terms of preserved mechanical function and reduced creatine kinase release. On reperfusion less oxidative stress developed. The beneficial effects of dimercapto-propanol could not be explained by hemodynamic differences or effects on energy metabolism. In addition, it is unlikely that dimercapto-propanol acts as a free radical scavenger at the concentrations employed. The protection may be achieved by the drug keeping some key sulfhydryl groups of functional proteins in the reduced state.
Sodium dimercaptopropanesulphonate (DMPS) and sodium dimercaptosuccinate (DMS) were discovered to be effective antidotes for acute poisoning of insecticides SCD [sodium ammonium dimethyl-2-(propane-1,3-dithiosulfate) monohydrate], nereistoxin (4-N,N-dimethylamino-1,2-dithiolane) and cartap (dihydronereistoxin dicarbamate). In mice, DMPS (250 mg/kg) or DMS (1000 mg/kg) ip 20 min before SCD increased LD50 of ig SCD from 97 to 374 or 251 mg/kg, respectively. The prophylactic effect of DMPS was better than that of DMS. Administration of DMPS prior to cartap increased LD50 of ig cartap from 130 to 375 mg/kg. The therapeutic effect of DMPS was also demonstrated in SCD-poisoned conscious rabbits. DMPS 62.5 mg/kg or DMS 500 mg/kg iv completely antagonized the neuromuscular blockade and respiratory depression caused by SCD, nereistoxin and cartap in anesthetized rabbits. The antagonism of SCD-induced neuromuscular blockade by cysteine (400 mg/kg, iv) was less effective and of shorter duration than that by DMPS and DMS. Dimercaprol 50 mg/kg im showed little effect on SCD-induced paralysis. The antagonistic actions of sulfhydryl compounds on neuromuscular blockade induced by these insecticides probably belong to chemical antagonism.
Based on some anecdotal case reports D-penicillamine (DPA) has been advocated for the treatment of arsenic poisoning. Experimental evidence, however, supporting that recommendation is lacking. In the present experiments the effectiveness of DPA was compared with dimercaprol (British Antilewisite, BAL), dimercaptopropanesulfonate (DMPS), and dimercaptosuccinic acid (DMSA) using different controlled experimental settings. In one study mice received As2O3 (9-14 mg/kg sc). Treatment with DMSA after 30 min afforded almost complete protection against the lethal effects of arsenic whereas DPA was not effective. In a second study, mice and guinea pigs were injected sc with 8.4 mg/kg As2O3 (containing a tracer dose of 74As). Thirty min later 0.7 mmol/kg of DPA or one of the other antidotes was injected ip. As determined 4 and 12 h after the arsenic injection, DPA was unable to reduce the 74As content in any of the organs investigated (blood, liver, kidneys, lungs, heart, brain, testes, spleen, skeletal muscle, and skin). On the other hand, BAL, DMPS, and DMSA markedly reduced the tissue content of 74As with respect to controls. Finally, the ability of the antidotes to reverse biochemical effects of arsenic was investigated in vitro using suspensions of incubated renal tubulus cells. The marked inhibition of gluconeogenesis induced by 30 mumol/L As2O3 was almost completely reversed upon addition of 90 mumol of either BAL, DMPS, or DMSA. In this experimental model, too, DPA was ineffective. It was concluded that the use of DPA in arsenic poisoning needs to be reevaluated.
A case of self-poisoning with sodium selenate sheep drench, along with blood and urine levels of selenium, is reported. Treatment included gastric lavage, diuresis, vitamin C, and dimercaprol, and the patient recovered without sequelae.
Therapy of acute heavy metal poisoning is currently limited to a group of moderately toxic drugs containing sulfhydryl groups. N-Acetylcysteine (NAC) was used in these studies to determine if this sulfhydryl containing amino acid would reduce the overall mortality of a group of heavy metal compounds. D-Penicillamine and dimercaprol (BAL) were also used for comparison. Groups of at least 100 mice (28 g) were injected subcutaneously with 2-190 mg/kg of copper, arsenic, thallium or cadmium for LD50 determinations. Other groups were injected 30-60 min later with NAC (200 mg/kg), d-penicillamine (50 mg/kg), or BAL (10 mg/kg), and mortality was monitored for 2 weeks. The LD50 for each treatment group was determined by regression analysis of log-probit transformed data. In arsenite treatment group the survival time was lengthened in NAC-treated animals although the LD50 was not significantly changed. BAL was only slightly more effective than NAC. The mortality in animals given copper and treated with NAC was almost eliminated, except at the highest doses. BAL provided the greatest protection, whereas d-penicillamine produced the least. The LD50 of copper was significantly changed from 60.5 mg/kg in control groups to 139 mg/kg in NAC-treated groups, and to 150 mg/kg and 91 mg/kg in BAL and d-penicillamine-treated groups. NAC and BAL were totally ineffective in the treatment of thallium and cadmium poisoning.
To investigate the possible role of hormones in gastric mucosal protection, the effect of prostaglandin F2 beta, dimercaprol, or cysteamine on ethanol-induced gastric erosions, and of cimetidine on gastric erosions caused by aspirin was studied in intact, adrenalectomized, medullectomized, ovariectomized, or thyroidectomized rats. Cimetidine was administered at a low dose that did not inhibit hydrogen ion secretion. Adrenalectomized animals failed to exhibit the usual mucosal protective response to prostaglandin F2 beta, sulfhydryls, or cimetidine. Ovariectomy or thyroidectomy did not influence mucosal protection with these agents. The inhibition by total adrenalectomy of mucosal protection was not reversed by large intragastric doses or by parenteral administration of prostaglandin F2 beta. Adrenal medullectomy alone significantly diminished (by approximately one-third) ethanol-induced gastric mucosal injury; prostaglandin F2 beta or sulfhydryl drugs produced significant additional protection. Replacement therapy with glucocorticoids (triamcinolone, corticosterone) but not with mineralocorticoids (deoxycorticosterone, 9 alpha-fluorocortisol) restored the cytoprotective effect of prostaglandin F2 beta and sulfhydryls in adrenalectomized rats. The generation of prostaglandin E2- and prostaglandin I2-like activity in the gastric mucosa was unaltered by adrenalectomy. These studies suggest a permissive role for glucocorticoids in gastric mucosal protection induced by prostaglandins, sulfhydryls, and cimetidine.
DMPS (2,3-dimercapto-1-propanesulfonate, Na salt) is an important water soluble analog of dimercaprol. All investigations of this antidote for heavy metal intoxication have dealt only with the racemic mixture. In the present report, the optical isomers of DMPS have been separated and the arsenic-antidote activity of the levo-rotatory (-)-isomer, the dextro-rotatory (+)-isomer and the racemic mixture of DMPS have been investigated in vivo and in vitro. The individual optical isomers and the racemic mixture of DMPS are effective equally, in vitro, in preventing the inhibition by sodium arsenite of the activity of mouse kidney pyruvate dehydrogenase complex. In addition, when pyruvate dehydrogenase is inhibited, in vitro, by sodium arsenite, any of the three DMPS preparations will reverse the inhibition equally well. The in vitro evidence suggests that two molecules of DMPS are required to prevent the effects of one molecule of sodium arsenite. Neither the LD50 nor the ED50 values of each of the three forms of DMPS differ significantly when measured i.p. in mice. In addition, there is no striking difference between the effectiveness of the levo- or dextro-rotatory DMPS when given orally to mice challenged with sodium arsenite. Thus, the use of the individual optical isomers of DMPS does not appear to have any advantage over the racemic mixture as an arsenic antidote under these conditions.
1. Thioctic acid used clinically in poisoning by A. phalloides, protected perfused livers and also isolated hepatocytes against phalloidin, when given in high concentrations. 2. Some SH-compounds like coenzyme A, dimercaprol, cysteine and cysteamine were found to be protective in different concentrations. 3. Rifampicin protects mice against lethal doses of phalloidin, and inhibits poisoning of isolated hepatocytes at low concentrations. 4. Some choleretic drugs like dehydrocholate, temoebilin (extr. cucumae xanth.), ethacrynic acid influenced phalloidin poisoning by inhibition of binding. 5. Doses of 0.2 to 4.0 mg dexamethasone added to 100 ml of perfusion medium did not protect perfused rat livers against 0.5 mg phalloidin. 6. Pretreatment of female rats with estrogens effected protection against phalloidin in vivo. The same procedure resulted in moderate decrease of phalloidin effects when the livers of pretreated animals were poisoned in vitro. In male rats estrogen pretreatment was less effective. Castration did not augment the protective effect. 7. Secophalloidin, a biologically inactive derivative, did not influence phalloidin poisoning in perfused livers, even when applied in excessive concentrations. 8. Concanavalin A, probably bound in the neighborhood of binding sites for phalloidin, did not protect perfused livers against phalloidin. 9 Diethyldithiocarbamate, a compound protecting livers against carbon tetrachloride and halothane, was ineffective in phalloidin poisoning. 10. Further protective actions of Evans blue, of some phenanthrolines and of EDTA are discussed. 11. Pretreatment of animals with hepatotoxic compounds (CCl4, CHCl3, cinchophen) decreased the toxicity of phalloidin in vivo. Possible mechanisms are discussed.