Term
| What are the 3 components of the membrane potential change from postganglionic cell bodies? |
|
Definition
1) rapid short-duration spike - EPSP (excitatory post synaptic potential)
2) hyperpolarization -IPSP (inhibitory post synaptic potential)
3) 1+ slower EPSPs of low magnitude |
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Term
| What component of the membrane potential change of postganglionic cell bodies is responsible for ganglionic transmission by inducing depolarization to fire APs? |
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Definition
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Term
| What mediates the first high EPSP? |
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Definition
|
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Term
| What 2 drugs can block the first EPSP? |
|
Definition
|
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Term
|
Definition
Several mechanisms:
1) DA released from accessory cells
2) Ach stimulation of M2 receptors |
|
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Term
|
Definition
| control/prevent excessive neurotransmission thru the ganglia |
|
|
Term
| What mediates the slower later EPSPs? |
|
Definition
| M1 receptors & peptide co-transmitter receptors |
|
|
Term
Receptor Affecting Peak/Low
[image] |
|
Definition
1) N
2) M2
3) M1 & Peptides |
|
|
Term
| What were the first effective drugs to treat hypertension? |
|
Definition
| ganglionic blocking drugs |
|
|
Term
| What is a classic ganglionic blocker that is effective in HTN treatment? |
|
Definition
| hexamethonium (not really used) |
|
|
Term
| What autonomic transmission is blocked by ganglionic blockers? |
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Definition
|
|
Term
| What SE is particularly marked in ganglionic blockers? |
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Definition
|
|
Term
| Why aren't ganglionic blockers used reeally anymore in anti-HTN Tx? |
|
Definition
| newer agents that are more selective |
|
|
Term
| What is the only ganglionic blocker still on the market? |
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Definition
|
|
Term
|
Definition
|
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Term
|
Definition
| block access for Ach to active site on AchE |
|
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Term
|
Definition
| precent breakdown of Ach => magnifying Ach response |
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Term
| What must be intact & functional for anticholinesterases to work? |
|
Definition
|
|
Term
| What are the 3 classes of anticholinesterases? |
|
Definition
|
|
Term
def
reversible anticholinesterase |
|
Definition
| agents that bind non-covalently to AchE active site or are slowly hydrolyzed by AchE => temporary inhibition |
|
|
Term
def
irreversible anticholinesterase |
|
Definition
| agents that form extremely stable covalent bonds with AchE esteratic site with long half lives (hours to days) => prolonged duration of action => sustained actions of Ach release |
|
|
Term
| What are the 8 reversible anticholinesterases? |
|
Definition
1) physostigmine
2) neostigmine
3) pyridostigmine
4) endrophonium
5) donepezil
6) tacrine
7) rivastigmine
8) galantamine |
|
|
Term
| What are the 4 irreversible anticholinesterases? |
|
Definition
1) echothiophate
2) malathion
3) parathion
4) sarin |
|
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Term
|
Definition
| irreversible anticholinesterases |
|
|
Term
| Which 2 reversible anticholinesterases are hydolyzed slowly by AchE? |
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Definition
|
|
Term
|
Definition
|
|
Term
| Fo what AchR does physostigmine act on it's AchE? |
|
Definition
|
|
Term
| What is the clinical use of physostigma? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What metabolizes physostigmine? |
|
Definition
| ester hydrolysis in plasma |
|
|
Term
Structure
Neostigmine & pyridostigmine |
|
Definition
| synthetic quaternary amines |
|
|
Term
Function
neostigmine & pyridostigmine |
|
Definition
AchE inhibitor
agonist for nAchR (due to charged amine) |
|
|
Term
| Though anticholinesterases need functional release of Ach to function, why would neostigmine (&pyridostigmine) still have some function (though muted)? |
|
Definition
|
|
Term
| Due to it's charged form, what are neostigmine & pyridostigmine used to treat? |
|
Definition
|
|
Term
| Does neostigmine have CNS effect? |
|
Definition
| No sicne it's a quarternary amine |
|
|
Term
| What are the clinical applications of neostigmine? |
|
Definition
1) augment GI/UT motility
2) reverse skeletal muscle blockade by competitive antagonists
3) Tx of myasthenia gravis |
|
|
Term
| What metabolizes neostigmine? |
|
Definition
|
|
Term
| Why does seostigmine need large oral does compared to parenteral dosage? |
|
Definition
|
|
Term
|
Definition
| skeletal muscle weakness that gradually becomes more intense thru the day & thru the years => eventually life threatening |
|
|
Term
|
Definition
| autoimmune disease where AB occupy nAchR on motor end plate |
|
|
Term
| How do anticholinesterases help myasthenia gravis patients? |
|
Definition
| improve strength of contraction |
|
|
Term
|
Definition
| synthetic quaternary amine |
|
|
Term
| What is the duration of action for edrophonium? |
|
Definition
|
|
Term
| How is edrophonium used clinically? |
|
Definition
| Dx of myasthenia gravis (excercise til muscle weakness present then administer edrophonium, if +, muscle stregth will resume for 5 min) |
|
|
Term
| How does pyridostigmine differ from neostigmine? |
|
Definition
| longer duration of action |
|
|
Term
| Why may a myasthenic patient become weaker during course of anticholinesterase therapy? |
|
Definition
1) exacerbation of disease
2) inadequate blood levels of anticholinesterase agent (myasthenic weakness)
3) overdose/toxic level (cholinergic crisis) |
|
|
Term
| What causes cholinergic crisis? |
|
Definition
| motor end plate is excessively stimulated by accumulating Ach & by direct action of neostigmine on motor end plast nAchR => membrane resting potential to be depolarized beyond threshold => depolarizing blockade & muscle weakness |
|
|
Term
| What will antagonize the muscle weakness in cholinergic crisis? |
|
Definition
| nerve stimulation or cholinergic agonist |
|
|
Term
| What is given to differentiate myasthenic weakness from cholinergic crisis? |
|
Definition
|
|
Term
| What effets would be seen by edorphonium in myasthenic weakness vs. cholinergic crisis? |
|
Definition
MW: improved muscle contraction
CC: intensified muscle weakness |
|
|
Term
| Why is edrophonium given over any other anticholinesterase to test b/w myasthenic weakness & cholinergic crisis? |
|
Definition
|
|
Term
| When might a person with myathenia gravis not benefit from anticholinesterase Tx? |
|
Definition
| If they are among the unlucky who have congenital mutations in nAchR |
|
|
Term
| Which anticholinesterase has FDA approval for prophylaxis against nerve gas exposure? |
|
Definition
|
|
Term
| What 4 anticholinesterases are used in Alzheimer's Tx? |
|
Definition
Donepezil
Tacrine
Rivastigmine
Galantamine
(Don'T foRGet) |
|
|
Term
| Why isn't tacrine used anymore? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
longer duration => once daily dosing
milder SE w/o hepatotoxicity |
|
|
Term
| What metabolizes donepezil? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| slow metabolism by cholinesterase & less DDI |
|
|
Term
|
Definition
| synthetic teritary alkaloid |
|
|
Term
| What Alzheimer drug is NOT a anticholinesterase? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why are irreversible anticholinesterase referred to as organophosphates? |
|
Definition
| they all contain a reactive phosphate group & some organic substitution |
|
|
Term
| When are irreversible anticholinesterase actually irreversible (i.e. no slow hydrolysis)? |
|
Definition
| if organic radical is an isopropyl substitution |
|
|
Term
| Why are organophosphids well absorbed through mucous membranes & skin? |
|
Definition
|
|
Term
| What is the only irreversible anticholinesterase used medically today? |
|
Definition
|
|
Term
| Why is echothiophate considered atypical? |
|
Definition
| polar & stable in aqueous solution |
|
|
Term
Effect
topical irreversible anticholinesterase on eye |
|
Definition
|
|
Term
| What does chronic use or irreversible anticholinesterase topically on the eye cause? |
|
Definition
|
|
Term
| What are the 2 most widely used organophosphates? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| When are malathion & parathion activated as anticholinesterases? |
|
Definition
| once bio-activated by liver |
|
|
Term
| Why is malathion used for home & garden insecticides & parathion is reserved for farming & other professional uses? |
|
Definition
| malathion is effectively detoxified by metabolism in mammals, parathion is not. |
|
|
Term
| How can malathion be used topically? |
|
Definition
|
|
Term
| Which insecticide is sprayed aerially to control mosquitos? |
|
Definition
|
|
Term
| How are all organophosphates excreted? |
|
Definition
|
|
Term
| What irreversible anticholinesterase poses the greatest threat of widespread poisoning? |
|
Definition
|
|
Term
| What causes death in anticholinesterase toxicity? |
|
Definition
any number of toxic SE (usually depends on route & rate of absorption)
1) CV collapse
2) asphyxia due to:
a) bronchoconstriction & secretion
b) paralysis of resp. muscles
3) CNS depression/coma |
|
|
Term
| What are the 6 toxic SE of anticholinesterases? |
|
Definition
1) Increased GI motility
2) Hypotension
3) Bronchial constriction & secretion
4) Involuntary micturition
5) CNS stimulation => convulsions => CNS depression/coma
6) muscle fasicluations followed by depolarizing blockade/paralysis |
|
|
Term
| What are the 3 parts of organophosphate poisoning Tx? |
|
Definition
1) decontamination (prevent further eposure)
2) atropine to control mAchR action
3) give an agent to promote regeneration of AchE s.a. pralidoxime |
|
|
Term
|
Definition
| binds anionic AchE site & phosphate moiety of organophosphate => permits bonds to be broken |
|
|
Term
| What happens if water is added to the organophosphate-AchE complex? |
|
Definition
| complex becomes "aged" and regeneration by pralisoxime will not occur |
|
|
Term
| Can pralidoxime reach the CNS? |
|
Definition
| no, it's a quaternary amine |
|
|
Term
| Patient is a 35 yo male admitted to ER with abdominal craming & vomiting. He was found slumped over a tractor in a fruit orchard. PE reveals him to be minimally responsive & shows cyanosis with marked resp. distress & hyperactive bowel sounds. He has bilateral miosis with extensive lacrimation & salvation with evidence of urinary incontinence. What is the problem? How should it be treated? |
|
Definition
| Organophosphate toxicity. Tx by decontamination, atropine, & pralidoxime. |
|
|
Term
MOA
pyridostigmine prophylaxis for nerve gas exposure |
|
Definition
| it binds to same site on AchE as organophosphate. If bound, then organophosphate can't bind. It won't protect DURING organophophate exposure, but once removed from exposure, pryidostigmine will be hydrolyzed off, preserving AchE function & therefore life |
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