L3 Flashcards
What kind of enzyme are cholinesterases?
Serine hydrolases
+ H2O to ester bond –> splits substrate
Which cholinesterase has activity towards acetyl-B-methylcholine?
AChE
Which cholinesterase is active against benzoylcholine & succinylcholine?
BChE
Can AChE or BChE be recovered by pralidoxime?
AChE
Where do you find AChE?
Nerve terminals
Muscle
RBCs
Where do you find BChE?
Plasma
Liver
Muscle
Brain
Inhibiting AChE or BChE can be fatal?
AChE
What are the 2 categories of reversible AChE inhibitors?
Mechanism - cleaved like ACh but serine active grp stays stable in the active site for some period of time
- Quaternary amines - reverses in seconds
- Edrophonium - Carbamates - reverses in minds
- Neostigmine
- Physostigmine
- Pyridostigmine
What is the irreversible AChE inhibitor? What does irreversible mean in this context?
Organophosphates - covalent bond formed with the enzyme so reverses slowly (hrs or days)
What would be the side effects of too much AChE inhibitors?
Excess ACh = para overstim = SLUDGE
Which drug would you use for paralytic ileus and bladder atony?
Neostigmine = block AChE
+
Bethanechol = M agonist
Inject to keep local - avoid non-selective problems (SLUDGE)
Which eye disease do you use anti-AChEs with muscarinic agonists for?
Glaucoma (NOT narrow angle)
Ex: physostigmine + pilocarpine
Increase ACh to M3 receptors - stretch iris = better fluid drainage
Why do you use anti-AChEs for MG? Which ones?
Neo or pyridostigmine
Increase ACh avail at NMJ where Nm have been destroyed by auto-immunity
What must you give with anti-AChEs for MG pts?
Anti-muscarinic
To avoid overstim para
What type of poisoning would you give anti-AChEs as therapy for?
Anti-muscarinic or nicotinic poisoning
Goal = try to increase ACh to competitively dislodge
Which anti-AChE do you give with anti-muscarinics to recover from neuromuscular block after surg? Why?
Neostigmine
Compete to dislodge the blocker!
How are anti-A/BChE drugs metabolized and excreted?
Metabolized by esterases
Excreted in urine
- Unconj
- Conj to sulfate or glucuronide
Contraindications for anti-AChE treatment
Same as M agonists
- Bronchial asthma
- Peptic ulcer
- Coronary insuff
- Hyperthyroidism
How are anti-AChEs used in a non-medical setting?
Pesticides
- Organophosphate insecticides require bioactivation
How do nerve agents like sarin gas work?
Organophosphates
Very hydrophobic –> penetrate skin easily
Large ACh block throughout the body with small dose
What is aging exhibited by nerve agent organophosphates?
Remains with AChE and changes during that time so can’t be displaced by PRALIDOXIME (2 PAM)
The enzyme is perm damaged - have to wait for liver to resynthesize more to regain fxn
How do you try to treat nerve agents?
2 PAM and atropine injection
