Transcript Document
Organic substances poisoning – metaldehyde, chlorinated hydrocarbons, tensides – surfactants, methylxantines Lecture No. 4 Copyright © Mgr. Zuzana Široká, PhD. Metaldehyde • Molluscocide - Snail bait • Very toxic, simple molecule • Usually peracute poisoning • Mechanism of action: decomposed to acetaldehyde depression of control centres in the brain, exact mechanism not known yet • Clinical signs: irritation to the stomach and intestines, anxiety, twitching, seizures – increased body temperature, death. Also excessive salivation, vomiting, diarrhoea, inability to control release of urine and faeces, increased heart rate, high blood pressure, incoordination, muscle tremors, rigidity and respiratory failure can occur • http://www.youtube.com/watch?v=lzY59qiUey I - liver failure syndrome occurs in some patients approximately 2 to 3 days after poisoning • Pathological examination: congestion and haemorrhages in the liver, kidneys and heart • Treatment: no specific antidote, emetics, activated charcoal, symptomatic Chlorinated hydrocarbons • Trichlorethylene, tetrachlorethylene, carbon tetrachloride, chloroform, methylene chloride etc. • All of them very lipophilic, cross blood-brain barrier, neurotoxic (CNS depressants) and hepatotoxic • Used as solvents, degrease agents, fuel additives etc. • Often inhalation poisonings, treatment only symptomatic Trichlorethylene - Colourless liquid of sweet taste and smell - Water insoluble, non-flammable - Used as a solvent of resins, rubber, tar, degreaser of metals - Rapid absorption, oxidation via CYP 450, accumulation in body due to strong protein binding and slow excretion - Necrotic effect, irritating mucosas, damage CNS - depressant, strong carcinogen! Tetrachlorethylene - Dry cleaner, degreaser, paint remover, solvent - Similar effect as trichlorethylene - Hepato- and nephrotoxic, suspected carcinogen Carbon tetrachloride - Colourless, volatile liquid of sweet smell - Excellent solvent, used in industry - Very toxic, damages liver and kidney, narcotic, carcinogen Tensides- surfactants • Agents with surface activity, form micelle, cause solubilization, detergents • Soluble in both organic solvents and water – due to the structure of their molecules • Class characteristics of tenside anionic, cationic, amphotheric and non-ionic tensides • Replace common soap – better frothing quality Division: • Ionic - Anionic (based on sulfate, sulfonate or carboxylate anions) Sodium dodecyl sulfate, ammonium lauryl sulfate and other alkyl sulfate salts, sodium laureth sulfate, soaps or fatty acid salts - Cationic (based on quaternary ammonium cations) Cetyl trimethylammonium bromide and other alkyltrimethylammonium salts, cetylpyridinium chloride, polyethoxylated tallow amine, benzalkonium chloride, benzethonium chloride - Amphoteric Dodecyl betaine, dodecyl dimethylamine oxide, cocamidopropyl betaine • Non-ionic Alkyl poly(ethylene oxide), copolymers of polyethylene oxide and polypropylene oxide - called poloxamers or poloxamines, alkyl polyglucosides - octyl glucoside and decyl maltoside, fatty alcohols - cetyl alcohol and oleyl alcohol, cocamide MEA, cocamide DEA, cocamide TEA • Problems they cause in the environment: - Strong frothing – foam covering huge areas of water sources, worsens cleaning efficiency in sewage treatment plants - Eutrophisation of water due to phosphates added to detergents - Xenoestrogennic effect – degradation product nonylphenol and other alkylphenols - Slow degradation - Decrease surface tension on gill, wash away mucus from it – easier infection, damages spawn • Toxicity for fish: anionic – 30 mg/l cationic – 3 mg/l – most toxic non-ionic – 10 mg/l Methylxanthines • Theobromine, theophylline and caffeine • In cocoa, chocolate, tea • Toxic for dogs and cats; toxic dose = approx. 40 to 400 grams of chocolate according to a size of the dog, dark chocolate most toxic • Theobromine: no therapeutic use, suspected mutagen Theophylline: is used as a bronchodilator Caffeine: analeptic effect, also suspected mutagen - all of them have negative effect on reproduction • Quickly absorbed, undergo enterohepatic circulation, slow metabolism, cross blood-brain barrier, excreted in urine • Mechanism of action: - in low doses: stimulate CNS and heart, slight diuretics, vasodilatation of coronary vessels - in excessive doses: a) inhibition of adenosine receptors in CNS – stimulation, tachycardia, vasoconstriction in brain, diuresis b) inhibition of phosphodiesterase – increased contractility of myocardium, increased glycolysis and lipolysis c) inhibition of Ca2+ resorption in sarcoplasmatic reticulum – also increased myocardial contractility • Clinical signs: - After 6 – 12 hours - Polydypsia, polyuria, vomiting, diarrhoea, tachycardia/arrhythmias, hypertension, hyperactivity, hyperthermia, ataxia, tremor, convulsions, coma, death - Due to high content of fat in chocolate, acute pancreatitis may be present too • Treatment: emetics, activated charcoal, monitoring of heart action, antiarrhytmic agents, diazepam in convulsions Grapes and raisins • Poisoning typical for dogs, but can probably appear also in cats and ferrets • Mechanism of action and toxic substance not known yet, but some scientists believe it is not a poisoning, but an idiosyncrastic reaction due to small amounts which sometimes lead to severe poisonings • Vomiting, diarrhoea, oliguria, anuria, lethargy, acute renal failure (tubular necrosis), death. Hops • Plant used for making beer • Exact mechanism and toxic substance not known. Probably uncoupling of oxidative phosphorylation. • Poisonings described only in dogs, most of the cases in greyhounds. • Typical symptoms are tachypnea, tachycardia, hyperthermia, seizures, death. Macadamia nuts • Poisonings described in dogs • Toxic substance as well as mechanism of action is unknown • Typical is weakness of rare legs • Other symptoms include vomiting, abdominal pain, ataxia, lameness, stiffness, recumbency, tremor, hyperthermia, joint and muscle pain and swelling • No lethal cases were described in healthy dogs • Symptoms may appear even in doses lower than 3 g/kg of body weight Onion and garlic • Formerly used as a home remedy against parasites • Contain disulfides (onion – allyl propyl disulfide, garlic – allicin) with antibacterial action, they are responsible for typical smell and irritation of eyes and lacrimation • Mechanism of action is oxidation of iron in haemoglobin and formation of methaemoglobin, then Heinz bodies formation, anaemia, renal damage • Signs involve pale membranes, tachycardia, tachypnea, lethargy, weakness, haematuria • Treatment – N-acetylcysteine is a donor of cysteine for glutathione, which helps in this type of oxidative injury; blood transfusion • More info: http://pmep.cce.cornell.edu/profiles/extoxnet/haloxyfopmethylparathion/metaldehyde-ext.html http://www.aspca.org/site/DocServer/toxbrief_0303.pdf? docID=621&AddInterest=1101 http://www.bmj.com/cgi/content/full/331/7517/633?q=y http://en.wikipedia.org/wiki/Surfactant http://www.ukmarinesac.org.uk/activities/waterquality/wq8_46.htm http://en.wikipedia.org/wiki/Trichloroethylene http://www.hsia.org/white_papers/tri%20wp.htm http://en.wikipedia.org/wiki/Tetrachloroethylene http://www.toxnet.nlm.nih.gov/cgibin/sis/search/f?./temp/~mK7y57:2