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Liver: • Centrilobular Necrosis • Fatty liver(steatosis) • Cirrhosis • Destroy P450 by destroying haem moiety • Neoplasia • Fibrosis • Non mutagenic carcinogen |
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Liver: • Necrosis • Fatty Liver(steatosis) |
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Liver: • Necrosis • Hepatocellular neoplasia • Tumors/neoplasia • Direct mutagen for carcinomas |
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Liver: • Necrosis • Steatosis • Heptaoceullar neoplasia • Canalicular cholestasis • Fibrosis • Dec heart contractility by interfering with Ca binding troponin |
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Liver: • Midzonal Necrosis • Attack Kupffer cells, Ito, and endothelial cells |
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Liver: • Periportal Necrosis |
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Liver: • Necrosis • Depletes GSH directly producing oxygen |
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Liver: • Water accumulation in hepatocytes(hydropic degeneration) > failure of sodium balance • Suicidal inactivation of P450 via reacting with detox enzymes Cardio: • artherosclerosis |
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Liver: • (gerbils) cirrhosis after repeat insults; mimics human secondary haemchromatosis • Hepatocyte death |
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Liver: • Initally attack Kupffer cells • Attacks Ito and endothelial cells |
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Liver: • Water accumulation • Steatosis • Non mutagenic carcinogen |
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Liver: • Centrilobular necrosis |
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Liver: • Centrilobular necrosis |
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Liver: • Centrilobular necrosis |
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Liver • Acute toxic porphyria
Dermal: • Photosensitivity • Biosynthetic pathway of heme is disrupted • Porphyrin pre-cursors accumulate→fluoresce when exposed to UV |
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Liver • Neoplasia Kidney: • Metabolized to phosgene • Necrosis of PCT epithelium • Chronic leads to tumors Cardio • Suppresses SA node • Sensitizes heart to adrenaline by reducing refractory period of Purkinjie • Tachycardia • Arrhythmias |
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Liver • Neoplasia • Cirrhosis • Vascular disorder • Steatosis • Hemorrhagic necrosis Lungs • Necrosis > cell proliferation > thickening of vasculature • Hypertension |
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Liver • Hepatocyte death • Vascular disoders |
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Liver • Canalicular cholestasis |
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aminoaryl niroaryl axoaryly |
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Liver • Non mutagenic carcinogen |
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Liver • Non mutagenic carcinogen
Neuro: • Acts on GABA receptor (stops inhibitory mechanism of GABA) • Prevents chloride ions from entering neurons > tremors and convulsions |
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Liver • Non mutagenic carcinogen |
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Liver • Non mutagenic carcinogen |
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Kidney: • Necrosis in PCT • Alters Calcium homeostasis • Inhibits cellular func by reacting with thiols in proteins • Glomerulonephritis • Chronic leads to tumors |
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Kidney: Cardio: • Hypertrophy • hypertensions |
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Kidney: • Acute necrosis of PCT |
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Kidney: • Intranuclear inclusion bodies Cardio: • Variety of degenerative changes in heart (cardiomyopathies) Neuro: • Peripheral neuropathy via attacking myelin • Learning deficits & dementia • Encephalopathy |
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Kidney: • Lesions in the PCT |
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Kidney: • Excessive accumulation of proteins(hyaline droplets) in epithelial of PCT • Renal adenomas • Necrosis with regeneration • Binds to alpha 2 globulins |
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Kidney: • Accum in lyso • Phospholipidosis • Mito damage • Tubular necrosis Cardio: • Inhibit Ca channels (slow inward movement) • Inhibits uptake and binding of Ca at sarcolemmal sites |
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Kidney: • Redox cycling > lipid peroxidation |
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Lungs: • Bronchoconstriction |
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Lungs: • Bronchoconstriction |
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Lungs: • Bronchoconstriction • Type 1 and 2 damage • Damage to capillaries • Necrosis of term bronchioles • Alveolar and interstitial edema • Fibroblasts and collagen syn • Intraalveolar fibrosis |
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Lungs: • Type I damage • Hypertrophy and hyperplasia of type 2 • Interstitial thickening • Inflammation and alveolar edema |
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Lungs: • Brochiolar necrosis • Chronic fibrosis |
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Lungs: • Alveolar and interstitial edema • Proliferation of fibroblasts • Metal complex leads to ROS and DNA damage |
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Lungs: • Sm. Muscle spasms |
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Cardio: • Opens Na channels |
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Cardio: • Blocks Na Channels |
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Cardio: • Blocks Na channels Neuro: • Blocks Na channels at presynaptic cleft • paralysis |
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Cardio: • Blocks Na channels |
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Cardio: • Blocks Ca channels |
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Cardio: • Dec heart contractility by interfering with Ca binding to troponin Isopropyl |
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Cardio: • blocks reuptake of catecholamines • inc heart rate and BP • sympathetic stim • cardiac arrest or seizures followed by respiratory arrest • Arrhythmias • Myocardial Ischemia • Hypertension • CHF • Inhibits Na channels- local anesthetic • Inc refractory period • Dec depolarization • Ventricular fibrillations • Myocyte necrosis(Myocardial Infarction) Neuro: • Blocks reuptake of catecholamines at axon terminals • Paralysis and Eurphoria |
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Cardio: • Artherosclerosis • Tachycardia • DEATH |
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Cardio: • Vascular spasms and BP • methemoglobin |
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Cardio: • Hemolytic anemia |
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Cardio: • Hemolytic anemia |
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Neuro: • Disrupt membrane ion transport in nerve axons • Prolong Na reflux and may block inhibitory pathways(pyrethroids) • Hyperexcitablity in and convulsions in insects; whole body tremors in mammals (type1) • Ataxia and incoordination in insects and paresthesias in humans(type 2) |
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cyclodienes(deldrin aldrin. chlordane) |
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Neuro: • Acts on GABA receptor (stops inhibitory mechanism of GABA) • Prevents chloride ions from entering neurons > tremors and convulsions |
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Neuro: • Acts on Na channel to cause “leakage” of Na ions • DDT Jitters> neuron fires impulses> muscle twitches> convulsions & death |
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Neuro: • Binds to tubules and stabilizes them preventing polymerization • Peripheral neuropathy • Stabilizes microtubules preventing disassociation |
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Neuro: • At axon terminals binds to nicotinic receptors> inc in HR and BP |
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Neuro: • Attacks soma • Dec in glycolysis, nucleic acid, and protein synthesis • Dementia, retardation, paralysis • Diffused encephalopathy |
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Neuro: • Presynaptic cleft: blocks liberation of Ach > paralysis • Breaks down SNARE complex at presynaptic cleft |
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Neuro: • At presynaptic terminal: interrupts fusion of vesicle to terminal wall • Paralysis |
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Neuro: • At presynapse: blocks Ach entering vesicles> no release of NT • Paralysis |
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Neuro: • At presynaptic cleft: blocking choline reuptake> preventing transmission • Paralysis |
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Neuro: • Blocks muscarinic receptors • Restlessness, irritability, hallucinogenicity |
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Neuro: • Blocks muscarinic receptors • Restlessness, irritability, hallucinogenicity |
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Neuro: • Binds to postsynaptic Ach receptor> prevents depolarization • Respiratory failure & paralysis |
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Neuro: • Attack myelin at Schwan cells>demyelination>paralysis • Myelinopathy |
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Neuro: • Encephalopathy with neurofibrillary degeneration via abnormal accumulation of neurofilaments and perinuclear region of neuron • Alzheimer’s and dementia |
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Neuro: • Contaminant in synthetic heroin • Metabolized to MPP+ in astrocytes→neurotoxic to dopamine neuron • Inhibition of oxidative phosphorylation |
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Neuro: • Decrease long and large diameter axons CNS & PNS→OPIDN |
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Neuro: • Reacts with amino groups to form pyrroles • Attacks neurofilaments causing swelling in distal axons • Transport is obstructed and degeneration occurs • “stocking and glove”→sensory loss of peripheral areas |
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vincristine & viniva(plant alkyloids |
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Neuro: • Peripheral neuropathies by depolymerizing tubules causing axonopathies |
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Neuro: • Peripheral neuropathies by depolymerizing tubules causing axonopathies • Binds to tubulin monomers preventing association into tubules |
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Neuro • Causes intramyelinic edema • Myelinopathy |
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Neuro • Accumulate outside the cells causing Ca to enter and cause neuronal damage→death • Targets neuronal and glial membranes |
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