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Old 03-26-2011
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Drug Practice Question: Pharmacology

A 6 year old male patient presents to the emergency room with his mother with severe vomiting, excessive salivation, urinary and bowel incontinence, and miosis. The mother is frantic and says that her son had gotten into one of their medicine cabinets and ingested some bug spray less than 2 hours ago. A drug that you administer to treat this condition acts in which of the following ways?

A. Binds to and inhibits an enzyme
B. Cleaves an effector molecule
C. Phosphorylates an effector molecule
D. Irreversibly binds to a receptor
E. Decreases the Vmax of an enzyme
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Old 03-26-2011
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Pralidoxime (2-PAM) is used for organophosphate intoxication to regenerate AchE. It binds to organophosphates and cleaves the covalent bond between organophosphate and AchE thus releasing the AchE.

I will vote for : B
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Old 03-27-2011
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D. Irreversibly binds to a receptor

Atropine
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Quote:
Originally Posted by doc_study View Post
D. Irreversibly binds to a receptor

Atropine
Atropine bind reversibly to Ach receptor on postsynaptic neuron. Increasing the amount of Ach in synaptic cleft (eg. administering AchE inhibitor eg Physostigmine) will displace atropin from the receptor. So I guess D is incorrect.
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Old 03-27-2011
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Quote:
Originally Posted by doc_study View Post
D. Irreversibly binds to a receptor

Atropine
time passed after exposure is very important here , otherwise atropine is perfect.
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Quote:
Originally Posted by harlesmd View Post
Atropine bind reversibly to Ach receptor on postsynaptic neuron. Increasing the amount of Ach in synaptic cleft (eg. administering AchE inhibitor eg Physostigmine) will displace atropin from the receptor. So I guess D is incorrect.
Atropine is a non-competitive or irreversible muscarinic blocker, it will not be displaced by inc. acetylcholine.


Quote:
Originally Posted by bronchiole View Post
time passed after exposure is very important here , otherwise atropine is perfect.
Yes i agree. I think thats the key to answer the question. Both options B & D are correct. We just have to figure out which drug we are using in this case.
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Quote:
Originally Posted by bronchiole View Post
time passed after exposure is very important here , otherwise atropine is perfect.
Exactly,2- PAM only works before the "aging" process occur on organophosphate (6-8 hours after intoxication). Atropine can be a good choice here to block the excessive cholinergic effects. However we can not pick D here because atropine do not bind irreversibly to the receptor. Atropine is a competitive inhibitor of Ach.
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  • There seems to be a little confusion over atropine - according to my textbook, emedicine, pharmgkb, and wikipedia, harlesmd is correct that atropine is a competitive antagonist.
  • It seems like the question is asking for pralidoxime by saying "less than two hours ago", and B certainly fits pralidoxime
  • D and E are sort of the same thing, so it's likely that neither of those would be correct
  • We would use both 2-PAM and atropine, right? C fits neither, so that's out. A sort of fits atropine, but B fits pralidoxime better
I would choose B.
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Old 03-27-2011
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Thanks guys for clearing this concept....
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Correct Answer B is correct!

Thanks for all of the responses. I made this question yesterday when reviewing pharmacology and I will admit it is a pretty difficult question because it tests multiple concepts. Although the timing in treatment for this case is important, you can answer this question without knowing that concept if you understand the mechanism of both drugs. Here is a more detailed explanation of the answer:

The case is describing organophosphate poisoning or cholinergic crisis (DUMBBELSS), which is generally treated with a combination of pralidoxime and atropine. Choice B is the correct answer in this case

Choice A describes the toxin, which is an organophosphate in this case. Insecticides can irreversibly bind to and inhibit Acetylcholinesterase

Choice B is the correct answer. This describes pralidoxime, which binds to the organophosphate and cleaves an alkyl group, thus releasing the molecule from acetylcholinesterase

Choice C is incorrect. This is not how Pralidoxime or atropine work

Choice D would be correct if it said “reversibly binds to a receptor” -> This describes atropine. Recall that atropine is a competitive antagonist of muscarinic receptors

Choice E describes the effect of an organophosphate on acetylcholinesterase. An irreversible inhibitor of an enzyme decreases both Vmax and Km. The effect of pralidoxime would be to increase the Vmax of Acetylcholinesterase by disinhibiting it
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thanx for the question
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Old 03-28-2011
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I think the only problem with this question is that most bug sprays contain permethrin, which binds to sodium channels therefore acts in different manner. Also I don't know if atropine is used as an insecticide/pesticide.
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