1.The antidotal effects of high-dosage gamma-aminobutyric acid on acute tetramine poisoning as compared with sodium dimercaptopropane sulfonate.
Peng, SUN ; Jiyuan, HAN ; Yuying, WENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(4):419-21
To investigate the therapeutic effect of high-dosage gamma-aminobutyric acid (GABA) on acute tetramine (TET) poisoning, 50 Kunming mice were divided into 5 groups at random and the antidotal effects of GABA or sodium dimercaptopropane sulfonate (Na-DMPS) on poisoned mice in different groups were observed in order to compare the therapeutic effects of high-dosage GABA with those of Na-DMPS. Slices of brain tissue of the poisoned mice were made to examine pathological changes of cells. The survival analysis was employed. Our results showed that both high-dosage GABA and Na-DMPS could obviously prolong the survival time, delay onset of convulsion and muscular twitch, and ameliorate the symptoms after acute tetramine poisoning in the mice. Better effects could be achieved with earlier use of high dosage GABA or Na-DMPS. There was no significant difference in prolonging the survival time between high-dose GABA and Na-DMPS used immediately after poisioning. It is concluded that high-dosage GABA can effectively antagonize acute toxicity of teramine in mice. And it is suggested that high-dosage GABA may be used as an excellent antidote for acute TET poisoning in clinical practice. The indications and correct dosage for clinical use awaits to be further studied.
Acute Disease
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Antidotes/*administration & dosage
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Antidotes/therapeutic use
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Bridged Compounds/*poisoning
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Random Allocation
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Rodenticides/*poisoning
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Unithiol/therapeutic use
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gamma-Aminobutyric Acid/*administration & dosage
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gamma-Aminobutyric Acid/therapeutic use
3.Toxicokinetics of tetramethylene disulphotetramine.
Hong-shun ZHANG ; Jing ZHOU ; Shou-lin ZHANG ; Yi-qun WU ; Cheng-ye SUN
Chinese Journal of Preventive Medicine 2005;39(2):91-94
OBJECTIVETo explore toxicokinetics of tetramethylene disulphotetramine (TETS) in rabbit and the effects on toxicokinetics of TETS after activated charcoal by gavage.
METHODSEight rabbits were exposed through gavage and vein respectively, the blood samples were collected from the center artery in ear of rabbit at an arranged time. Four rabbits were exposed after being intubated into urethra and common bile duct. The samples of bile and urine were collected at arranged times. After being exposed by gavage, activated charcoal (1 g/kg) was administrated in the activated charcoal group and the distilled water (1 g/kg) administrated to the controls. The samples of blood were collected from the center artery in ear of rabbit at arranged times. The contents of TETS in samples were determined by GC/NPD method. Analysed by the 3p87 soft, toxicokinetics parameters of TETS were acquired.
RESULTSTETS was eliminated very slowly in rabbit. The plasma half time in elimination phase (Tke1/2) of TETS was 56.9 hours in vein exposure group and 262.5 hours in oral exposure group respectively. The plasma clearance (CL) of it was only 15.4 ml.kg(-1).h(-1) in oral exposure group and 24.1 ml.kg(-1).h(-1) in vein exposure group. TETS was eliminated from urine in rabbit. The eliminated amount of it from urine was more 5 times than from bile. All parameters of toxicokinetics of TETS were significantly different between the activated charcoal group and the control. Compared to the control, Tke1/2 of TETS in the activated charcoal group was equal to 55%, CL was increased over 3-fold, area under the curve was equal to 30%.
CONCLUSIONTETS was a poison eliminated very slowly in body. The eliminated amount of it from urine was more than from bile. The excretion of TETS could be quickened after activated charcoal by gavage.
Animals ; Antidotes ; administration & dosage ; Bile ; metabolism ; Bridged-Ring Compounds ; blood ; pharmacokinetics ; urine ; Charcoal ; administration & dosage ; Female ; Male ; Metabolic Clearance Rate ; drug effects ; Rabbits
4.Potentially fatal paracetamol overdose and successful treatment with 3 days of intravenous N-acetylcysteine regime--a case report.
Ashish A SULE ; Dessmon Y H TAI ; Choong-Charn TZE ; Balakrishnan DEEPA ; Melvin Khee-Shing LEOW ; Melvin LEOW
Annals of the Academy of Medicine, Singapore 2006;35(2):108-111
INTRODUCTIONParacetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g.
CLINICAL PICTUREWe describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L).
TREATMENTShe was treated with a 3-day modified regimen of intravenous N-acetylcysteine.
OUTCOMEThe liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day.
CONCLUSIONFrom this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.
Acetaminophen ; blood ; poisoning ; Acetylcysteine ; administration & dosage ; Adult ; Amylases ; blood ; Antidotes ; administration & dosage ; Codeine ; poisoning ; Drug Overdose ; Female ; Humans ; Liver Function Tests ; Narcotics ; poisoning ; Suicide, Attempted ; Tablets ; Time Factors
5.Mercury inhalation poisoning and acute lung injury.
Hong Euy LIM ; Jae Jeong SHIM ; Sang Yub LEE ; Sin Hyung LEE ; Sei Yong XYong KANG ; Jae Yun JO ; Kwang Ho IN ; Han Gyum KIM ; Se Hwa YOO ; Kyung Ho KANG
The Korean Journal of Internal Medicine 1998;13(2):127-130
Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is usually fatal because of progressive pulmonary failure. We experienced a patient with acute respiratory distress syndrome (ARDS) after illicit use of mercury vapor for hemorrhoid treatment; he developed acute chemical pneumonitis following exposure to mercury vapor. Prompt treatment with corticosteroids and penicillamine for acute chemical pneumonitis was instituted; radiologic pulmonary infiltrates disappeared within a week, but late phase neurologic sequelae and pulmonary interstitial fibrosis progressed.
Adrenal Cortex Hormones/administration & dosage
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Aged
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Antidotes/administration & dosage
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Disease-Free Survival
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Human
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Inhalation Exposure/adverse effects*
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Male
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Mercury Poisoning/diagnosis
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Mercury Poisoning/complications*
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Penicillamine/administration & dosage
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Respiratory Distress Syndrome, Adult/drug therapy
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Respiratory Distress Syndrome, Adult/chemically induced*
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Substances:Penicillamine
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Substances: Antidotes
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Substances: Adrenal Cortex Hormones
6.Treatment of Wilson's disease with penicillamine and zinc salts: a follow-up study.
Ming LI ; Yue-hua ZHANG ; Jiong QIN
Chinese Journal of Pediatrics 2003;41(2):119-122
OBJECTIVEWilson's disease (WD) is an autosomal recessive disorder characterized by excessive accumulation of copper in the liver and later in the brain and other organs. Penicillamine acts as a reductive chelator. Zinc salts induce the synthesis of metallothionein in cells. Thus these two drugs are theoretically synergistic for the treatment of the disease. However, the two drugs may also have some unfavorable interactions. In this study, the effect of the therapy with combined penicillamine and zinc salts was evaluated based on the follow-up observations of 21 patients with Wilson's disease.
METHODSUsing the combined therapy of penicillamine [10-30 mg/(kg.d)] and zinc (22.5 mg, 3 times per day), follow-up study by hospitalization or communication with telephone or mail.
RESULTSBefore treatment, all the 21 patients were suffered from chronic liver disorder. Among them, 13 patients (62%) showed to be reactive to the treatment for their liver disorder, 5 patients (24%) died, and 3 patients (14%) dropped off our follow-up study. Among the 5 patients who died, 3 died within 40 days after treatment, one had taken penicillamine only 8 mg/(kg.d), and one died after discontinuation of the treatment by the parents. Of the 12 patients having neurological involvement, neurological symptoms disappeared or markedly improved in 11 patients after treatment. One patient dropped off the follow-up study. The patient with renal tubular acidosis responded well to the treatment. Urine routine analysis was followed up in 6 of the 7 patients with hematuria. Hematuria disappeared in one, became less severe in 1, and remained unchanged in 4 patients. Hypersensitivity to penicillamine was found in one patient. WBC and platelet were found decreased further in 3 patients after the medications.
CONCLUSIONSThe combined therapy with penicillamine and zinc salts was effective in treatment of patients with Wilson's disease.
Adolescent ; Antidotes ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Hepatolenticular Degeneration ; drug therapy ; Humans ; Male ; Penicillamine ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome ; Zinc ; administration & dosage ; adverse effects ; therapeutic use
7.Effect of pre-treatment of alpha-ketoglutarate on cyanide-induced toxicity and alterations in various physiological variables in rodents.
Rajkumar TULSAWANI ; Deo KUMAR ; R BHATTACHARYA
Biomedical and Environmental Sciences 2007;20(1):56-63
OBJECTIVETo investigate the effects of pre-treatment of alpha-ketoglutarate (alpha-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents.
METHODSThe LD50 of potassium cyanide (KCN) given orally (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence alpha-KG given po, ip or iv. alpha-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of alpha-KG (protected animals) and LD50 of KCN in the absence of alpha-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) alpha-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po).
RESULTSPI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with a-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg alpha-KG given ip (-10 min), respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg alpha-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg alpha-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of alpha-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of alpha-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of alpha-KG (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy of alpha-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv administration of alpha-KG.
CONCLUSIONSCyanide antagonism by alpha-KG is best exhibited when both alpha-KG and KCN are given by po route. The protective effect of a-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of alpha-KG as an alternative cyanide antidote.
Administration, Oral ; Animals ; Antidotes ; administration & dosage ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Injections, Intravenous ; Injections, Subcutaneous ; Ketoglutaric Acids ; administration & dosage ; Lethal Dose 50 ; Male ; Mice ; Potassium Cyanide ; poisoning ; Rats ; Rats, Wistar
8.A case of methemoglobinemia after ingestion of an aphrodisiac, later proven as dapsone.
Seoung Woo LEE ; Ji Young LEE ; Kyung Joo LEE ; Myungsoo KIM ; Moon Jae KIM
Yonsei Medical Journal 1999;40(4):388-391
Methemoglobin (MetHb) is an oxidation product of hemoglobin in which the sixth coordination position of ferric iron is bound to a water molecule or to a hydroxyl group. The most common cause of acquired MetHb-emia is accidental poisoning which usually is the result of ingestion of water containing nitrates or food containing nitrite, and sometimes the inhalation or ingestion of butyl or amyl nitrite used as an aphrodisiac. We herein report a case of MetHb-emia after ingestion of an aphrodisiac, later identified as dapsone by gas chromatograph/mass selective detector (GC/MSD). A 24-year old male was admitted due to cyanosis after ingestion of a drug purchased as an aphrodisiac. On arterial blood gas analysis, pH was 7.32, PaCO2 26.8 mmHg, PaO2 75.6 mmHg, and bicarbonate 13.9 mmol/L. Initial pulse oxymetry was 89%. With 3 liter of nasal oxygen supplement, oxygen saturation was increased to 90-92%, but cyanosis did not disappear. Despite continuous supplement of oxygen, cyanosis was not improved. On the fifth hospital day, MetHb was 24.9%. Methylene blue was administered (2 mg/kg intravenously) and the patient rapidly improved. We proved the composition of aphrodisiac as dapsone by the method of GC/MSD.
Administration, Oral
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Adult
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Antidotes/therapeutic use
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Aphrodisiacs/adverse effects*
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Case Report
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Cyanosis/drug therapy
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Cyanosis/chemically induced
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Cyanosis/blood
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Dapsone/adverse effects*
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Human
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Male
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Methemoglobinemia/drug therapy
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Methemoglobinemia/chemically induced*
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Methylene Blue/therapeutic use