Term
| Forms of acetyl cholinesterase |
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Definition
Brain: catalytic subunits bound to membrane anchoring protein
Muscle: tetramers of catalytic subunits linked via long, collagen-like tails that are anchored to the basement membrane
Plasma: 'psuedo' cholinesterase which cleave a variety of esters and are active towards butyrylcholine (not used as a drug) (note that RBCs contain 'true' AChE) |
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Term
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Definition
Quaternary amine: Simple competitive inhibitor
Edrophonium
Carbamates: competitive inhibitors that undergo slow hydrolysis
Physostigmine
Neostigmine
Pyridostigmine |
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Term
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Definition
| Quaternary amine with brief duration (1-5 mins). Used to test for myasthenia gravis where IV administration causes a brief improvement of strength. Also used to judge correct dosage: if brief improvement is seen with use that patient may benefit from a higher dose of carbamate. |
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Term
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Definition
| Crosses BBB into CNS, used for treatment of wide-angle glaucoma, often with pilocarpine. Used to treat atropine overdose ('PHYxes' atropine overdose). Can adversely facilitate formation of cataracts. |
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Term
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Definition
| Short lasting (0.5 - 2hr). Used to treat loss of tone in GI tract and bladder (urinary retention) either from disease or from postoperative recovery from anesthesia. Also used for myasthenia gravis. No CNS penetration ('NEO' CNS penetration). |
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Term
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Definition
| Used to treat myasthenia gravis, longer duration (3-6hr) than neostigmine. |
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Term
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Definition
| Similar to pyridostigmine but even longer acting (4-8hr). |
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Term
| Irreversible AChE inhibitors |
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Definition
| Also termed organophosphates, form highly stable (covalent) phospho-intermediates. Take up to hundreds of hours to be cleaved off of enzyme. Before 'aging' is sensitive to nucleophilic attack by an oxime such as pralidoxime. After 'aging' is no longer susceptible. |
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Term
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Definition
| Used to treat glaucoma (third-line), only clinically useful organophosphate. |
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Term
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Definition
| Insecticides responsible for many cases of farm poisonings. Converted to malaoxon and paraoxon, respectively, which are more toxic compounds. Detoxified in mammals and birds via plasmaesterases. |
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Term
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Definition
| 'Nerve gases' that are potent inhibitors of AChE, among the most toxic agents known. |
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Term
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Definition
| Used in treatment of Alzheimer's. Long acting (once-a-day dosing), CNS penetrant, good oral absorption. |
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Term
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Definition
| Carbamate similar to physostigmine used to treat Alzheimer's. Requires twice-a-day dosing. |
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Term
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Definition
| Long-acting drug for Alzheimer's. Not only a AChE-I but also a potent allosteric enhancer of CNS nicotinic receptors. |
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Term
| AChE inhibitor toxicity and symptoms |
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Definition
| Mixture of muscarinic, nicotinic and CNS effects. 'SLUDGE-BAM': salivation, lacrimation, urination, defecation, GI upset, emesis, bradycardia, bronchoconstriction, bowel movement, abdominal cramps, anorexia, miosis. (Also DDUMBBELSS) |
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Term
| Organosphophates vs. Carbamates |
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Definition
| Organophosphates are longer-lasting and tend to have nicotinic excess symptoms, whereas carbamates tend to have more muscarinic symptoms. |
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Term
| Mechanism of lethal AChE-I overdose |
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Definition
| Death is usually from respiratory failure due to bronchoconstriction, bronchorrhea (high volumes of sputum production), central respiratory distress, and weakness or paralysis of respiratory muscles. |
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Term
| Treatment of AChE-I poisoning |
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Definition
| Mixture of atropine (muscarinic blocker) and pralidoxime (regenerator of un-'aged' enzyme), with diazepam to prevent convulsions. |
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