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22 Cards in this Set
- Front
- Back
Organophosphorus Compounds
Irreversible AChE Inhibitors Therapeutic Agents |
Echothiophate
Diisoprophyl |
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Irreversible AChE Inhibitors
Insecticides |
Tetraethyl pyrophosate
Parathion Malathion |
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Irreversible AChE Inhibitors
Nerve Gases |
Sarin
Soman Tabun |
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Irreversible AChE Inhibitors MOA
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Irreversibly phophorylate (hence inactivate) AChE
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If we irreversibly inactivate AChE, what effect will that have on ACh?
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ACh will stay too long --> adverwe effects whih will be lethal
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Diisopropyl Fluorophosphate
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DFP
High lipid solubility Volatile |
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Echothiophate
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Positively charged
not volatile Preferred over DFP |
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what are the therapeutic uses of DFP and echothiophate?
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Miotic
Glaucoma These are drugs of last resort |
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What is important about insecticides?
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Most of organophosphates are well aborbed from the skin, gut, and conjuctiva --> dangerous to humans
Limited half life when dissolved in water |
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What is Parathion?
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Insecticide
Not used clinically Major problem with accidental poisoning. |
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What is Malathion?
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Insecticide
Low dermal absorption Detoxified by plasma carboxylesterases more rapidly in mammals and birds than in insects Used clinically to treat head lice |
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What is the range of toxicity in the irreversible AChE inhibitors?
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Malathion < Parathion <<<< Sarin
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What are the adverse effects of AChE inhibitors?
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Lens opacities (echothiophate)
Chronic neurotoxicity Cholinergic overstimulation Cholinergic crisis |
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How does triorthocresylphosphate (an additive in lubricating oils) causes chronic neurotoxicity?
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Triorthocresylphosphate --> inhibits neurotoxic esterase --> axonal swelling & demylenation --> sensory disturbances, ataxia, weakness, tendon reflexes, muscle twitching, reduced tenderness
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What can ACh do?
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Stimulate M receptors at effector organs.
Stimulate cholinergic receptors in the CNS Produce stimulation followed by depression or paralysis of autonomic ganglia and skeletal muscle |
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What is the difference between neostigmine, physostigmine, and the organophosphates?
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Neo--reversible, doesn't cross BBB
Physostigmine--reversible, crosses BBB Organophosphates--irreversible, crosses BBB |
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What effects will be caused by cholinergic overstimulation/crisis?
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Miosis
spasm of accommodation Extreme salivation Sweating Bronchoconstriction Vomiting Diarrhea Bradycardia Hypotension Urinary urgency |
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What are the CNS effects of cholinergic overstimulation/crisis?
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Confusion
Ataxia Slurred speech Loss of reflexes Convulsions Coma Central respiratory paralysis |
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What are the skeletal muscle effects of cholinergic overstimulation/crisis?
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Involuntary twitching
Severe weakness Paralysis |
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What is the cause of death in the cholinergic overstimulation/crisis?
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Respiratory failure and cardiovascular collapse
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What is the treatment of cholinergic crisis?
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Sarin --> excessive activation of M/N receptors (both central and peripheral)--> central (muscarinic blocker--atropine) and peripheral (cholinesterase reactivator--2-PAM)
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What is cholinesterase reactivator?
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Pralidoxime (2-PAM)
NMJ Autonomic ganglia peripheral effector sites Used only for organophosphate poisoning |