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Suez Canal University Faculty Of Veterinary Medicine Department Of Forensic Medicine & Toxicology Second Term Exam Of Toxicology Date: 14/06/2009 i. Time: 2h Answer the following questions: (10 marks) a. NADH is the major reducing equivalent in the mitochondria and is used to reduce oxygen to water and synthesis of ATP, hence inhibition of production of NADH by xenobiotics can occur at several distinct sites. (give comment on previous statement & suggest antidotal therapy for one of these offending chemicals. (5 marks). Answer: This as in case of cyanide toxicity and carbon monoxide toxicity where the toxic compounds make inhibition to cytochrome oxidase enzyme that lead to inhibition of electron transport chain in mitochondrial and inability to reduce oxygen into water and ATP is not formed in this case leading to depletion of energy and tissue anoxia. Also aconitase can be inhibited by fluroacetate that can be used as rodenticide which stop kreb’s cycle. The suggested antidotal treatment of cyanide poisoning is by using sodium nitrate intravenous injectin which lead to formation of met Hb which combine with cytochrom oxidase cyanide complex. An adminsteration of sodium thio sulphate orally it will react with cyanomet Hb releasing Hb + Sodium sulphate + thiocyante ( stable and ready to be excreated). b. procedure for enhancing termination of action of chemicals requires an increase the slope of descending portion of the toxic curve. Can you explain how you design a plan to achieve your aim? ( give example to support your procedure). (5 marks). Answer: We can terminate the action of chemicals by: 1- decrease slope of ascending portion ( decrease absorption). 2- Increase slope of descending portion ( increase excreation). 3- Elevation of toxic threshold. This can be done by: 1- washing of skin and prevent further exposure to toxic chemicals if this chemical absorbed via skin. 2- If absorbed via the lung it can be reduced by stimulation of respiration in case of toxic gases to remove it from blood. 3- If absorbed via GIT we can reduce absorption by gastric washing using stomach tube and use water or alcohol according to type of chemical poison to dissolve and diltue and help in excreation of it rapidly. 4- Using emetic as Ipecac ( stomach irritation) or apomorphine (central emetic). 5- Using of chelating agents to enhance excreation and bind to unbound part of chemical toxin and prevent its uptake by tissue. VD (volume of distribution) = dose / plasma concentration So when plasma concentration of toxic substance increase the volume of distribution will be little. An example for chelating agents is 2-PAM (oxime)(pyridine2-aldoxime methyl chloride) which used in case of organophosphrous compounds toxicity as parathion which converted from non toxic to toxic in liver and become paraxol. Also EDTA can be used in case of lead, penicillamine can be used in case of copper ( most common), lead and mercury. 6- also PH can control toxin excreation from body for example : amphetamine in racing horses (alkaline) given with sodium bicharbontae which is alkaline reducing its excreation and increase its absorption internal tubules so remain high in level in plasma, but in case of toxicity with acidic chemicals as barbiturates you can use alkaline substances to increase its excreation. Elevation of toxic threshold can be done by: 1- opposing action of chemical in body for example drugs which may depress respiration, we must give drugs that antagonize its action if toxicity will occur. 2- Drug replace the site of action of chemical ( atropine in case of acetylchloine and toxicity of organophosphrous compound toxicity). ii. choose the correct answer : (15 marks) 1- enhancement of alkaloid by: (decreasing PH) 2- BAL is an antidote for: (all) 3- lead can be treated by: (mono calcium disodium EDTA) 4- chelation is a process for: (treatment) 5- elevating toxicity threshold is carried out by: (all) 6- treatment of morphine by: (both) 7- cyanide intoxication can be treatment by: (sodium nitrite) 8- the universal antidote is: (activated charcoal only) 9- ANTU increase permeability of blood vessels of: (lung) 10- strychnine: (site of glycine inhibitory transmitter) 11- thalium inhibits enzymes containing: (SH) 12- warfarine inhibits: (K2 3 epoxide reductase) 13- vacor antagonise: (NAD) 14- zinc phosphide release: (phosphine) 15- muscarine affects: (all) 16- emetic of choice is: (Ipecac) 17- type II pyrethroide contain: (CN) 18- pyrethroide is an ester of: (pyrethric acid) 19- VX type of nerve gas intoxication can be treated by: (none) 20- pyrothroide delay closure: (of sodium channel) 21- DDT is stored: (fatty tissue) 22- atropine can be used for treatment of: (all) 23- enhancement of salicylic acid excreation is carried out by: (change PH to alkaline) 24- Di methyldithiocarbate chelate: (ZINC) 25- penicillamine is a drug of choice in : (copper) 26- treatment of LAAS by adminsteration of: (vitamine K) 27- pyrothroide prevent the relaese of neurotransmitter through: (prevent calcium entery) 28- pyruvic oxidase enzyme is inhibited by: (none) 29- hydrolytic cleavage is: (increasing hydroliphilicity of the toxic chemical) 30- addition of COOH group to toxin increase: (hydrophilicity)