QUESTIONS

1. What does acetylcholinesterase do?
    
2. In which neurons is acetyl choline a neurotransmitter?
    
3. Which receptors are muscarinic & which are nicotinic?
    
4. Considering how there would be increased muscarinic & nicotinic firing, what kind of signs would one see in OP toxicity?
    
5. What is the best test in the live animal?  How about in the dead animal?
    
6. How does Atropine help in the treatment of OP tox?  How does benedryl help?
    
7. What does the term "aging" refer to in OP tox?
   
   
   
   
    

ANSWERS

1. Acetylcholinesterase is one of several enzymes (as far as I can tell they are all affected by OPs) that breaks acetyl choline into choline & acetic acid.  The site of this occurance is at the receiving end of a synapse. Acetylcholinesterase breaks up ACh so that the receiving nerve can stop being stimulated after its message has been received.
   
   
   
   
    
2. Acetyl choline is the neuro transmitter for 1) any nerves that have cell bodies in the spinal cord (so this includes somatic nerves, and preganglionics from the symp NS & preganglionics from the parasymp NS).
   
   Recall that in the symp NS, the preganglionics are short & the ganglia are located near the thoracic & lumbar cord segments.  The postganglionics are long & end on target organs. The neurotransmitter at the target organ would be norepi & the like.  Receptors are said to be either alpha or beta.
   
   In the parasymp NS, preganglionics are long & ganglia are near the target organs.  The postganglionics area short & end on target organs.  The neurotansmitter here is ACh again.
   
   
   
   
    
3. Receptors in ganglia are nicotinic, whether they are symp or parasymp.  Parasymp receptors on the target organ are muscarinic.
   
   
   
   
    
4. Classically, one sees SLUD (salivation, lacrimation, urination, diarrhea)  vomiting & pinpoint pupils are also popular.  There is respiratory depression from effect on the diaphragm & resp. muscles (& this is generally how one would die).
   
   
   
   
    
5. In the live animal you want to submit whole blood in EDTA or heparin for a cholinesterase level.  A level <25% normal indicates a high exposure to the toxin.  Keep in mind though that cats are especially good at looking clinically normal with levels <10% of normal so it is easy to be misled.
   
   Cats also have the ability to get a chronic form of OP toxicity & CVT12 recommends that cholinesterase levels be included in the work up of any cat w/chronic anorexia or weakness.
   
   In the dead animal you either need brain or eyeball (eyeball is easier).  But the body must be frozen ASAP after death or there won't be anything left to test for.
   
   
   
   
    
6. Atropine helps with the muscarinic signs (SLUD) by blocking receptors in these areas (it's parasympatholytic, remember?).  It doesn't help reactivate the cholinesterase; it only helps compete with all the excess ACh floating around.
   
   Bendryl is said to help with the nicotinic effects (resp depression).
   
   
   
   
    
7. Let's review the active site of cholinesterase.  It has an anionic site & an esteratic site.  The Nitrogen group on the ACh molecule is attracted to the anionic site & is held there by a hydrogen bond.  Next the esteratic site covalently bonds to the carbonyl group onf hte ACh. The choline splits off (this is the nitrogen part) & a water molecule comes in & carries acetic acid away.  The enzyme is then ready to go again.
   
   If you throw in a carbamate:  the carbamate does all of the above just like ACh does but when the enzyme is acting on a carbamate instead of ACh, the reaction occurs VERY SLOWLY.  So slowly that the enzyme is effectively removed from the pool of active enzymes (though eventually it regenerates).
   
   If you throw in an OP:  the OP ignores the anionic site & bonds to the esteratic site thus permanently phosphorylating the enzymre.  Bummer.  Aging occurs in the next couple of hours where the PO4 group rearranged to more stably bind to the enzyme.  Prior to aging, the phosphorylated enzyme can be saved by 2-PAM.
   
   2-PAM is very nucleophilic & will attach the PO4 group.  The PO4 group is thus bumped off the enzyme leaving 2-PAM stuck on the enzymre.  2-PAM detaches w/ease & the enzyme is functional again.
   
   I want to note, though, that my vet school notes say that only OP's manufactured for chemical warfare undergo aging. Anything you might actually use at home doesn't "age" & 2-PAM will work any time.