Term
| How does differential RNA processing change anti-cholinesterase activity? |
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Definition
| Affects targeting, but NOT catalytic site. |
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Term
| What is the mechanism of action of reversible, long-lasting, anti-cholinesterase drugs such as neostigmine? |
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Definition
Act as false substrates. Bad for diagnosis, Good for treatment of chronic conditions
1) Bind ACh
2) Serine on drug attacks ester bond and kicks off choline, creating an acetyl intermediate
3) Water kicks off acetate |
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Term
How does the action of irreversible anti-cholinesterases differ from reversible drugs?
How then can you deal with exposure to nerve gas and certain insecticides? |
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Definition
1) In the irreversible case, phosphoryl-enzyme intermediates are produced that are not sensitive to hydrolysis in vivo.
2) Give Pralidoxone for peripheral and Atropine for central in order to chemically displace phosphoryl group to reactivate enzyme. |
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Term
| Why might you give an irreversible anti-cholinesterase clinically? |
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Definition
| To treat gluacoma, by decreasing intraocular pressure created by the vitreous humor ( |
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Term
| How would you diagnose/treat Myasthena gravis |
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Definition
1) Perform tensilon test with short-acting anti-cholinesterase like edrophonium
2) If positive, that means antibodies are most likely attacking AChR.
Give anti-cholinesterase along with atropine to avoid muscarinic side effects in heart, lungs and glands |
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Term
| How can you tell why a patient with M. gravis is not responding to anti-cholinesterase treatment? |
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Definition
Could be 2 things
Usually can tell by muscarinic side effects- EXCEPT if you added atropine
1. low levels of drug
2. if levels of drug are high due to tonic depolarization and sodium channel inactivation (should see muscarinic side effects) |
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Term
| 3% of M. Gravis cases are congenital. What is the molecular basis? |
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Definition
| Not enough LOCALIZED receptor at the NMJ, because of change in Colq tail. |
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Term
| Why can kids exhibit what looks like atropine poisoning? |
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Definition
| Anti-histamine effects mimic anti-muscarinic drugs |
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Term
| What is thought to be the basis for Gulf War Syndrome? |
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Definition
1) Soliders in war injected pyridostigmine to protect against nerve gas
2) These organophosphates may have led to de-myeination and axon loss, by inhibiting neuropathy target esterase (NTE) |
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Term
| What are Pseudocholinesterases? |
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Definition
Plasma enzymes synthesized in the liver that metabolize ACh, succinylcholine and ester local anesthetics
** Can cause differences in individual drug sensitivity or time course** |
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Term
| Why might you give anti-cholinesterase after surgery? |
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Definition
To displace competitive NMJ blockers used to induce paralysis
** Won't work for succinylcholine, with is depolarizing and non-competitive** |
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