Anti-cholinesterase Drugs Flashcards
Which drug is a tertiary amine (NH3) and what makes it unique?
Physostigmine
- lipophillic and small enough to cross the BBB
Which drugs are quaternary ammoniums (NH4)?
Edrophonium
Neostigmine
Pyrostigmine
Which organs can Ach go to?
Heart
Gut
Lungs
How do anti-AchE drugs work?
- inhibit acetylcholinesterase
—> result in increased availability of Ach at neuromuscular junction, muscarinic receptors, and autonomic ganglia
What happens if anti-AchE meds are given when NMB not there?
Will cause fasiculations/overstimulation- in large doses
How do neostigmine and pyridostigmine reverse NMBs?
- hydrolyzed by AchE (enzyme)
- carbamalates the enzyme is the process
- blocks enzymes ability to hydrolyze Ach
(Interferes with the breakdown of Ach, neostigmine
Indirectly stimulates nicotinic and muscarinic receptors)
How does Edrophonium work?
Forms a reversible elecrostatic attachment
What are the different classifications for AchE inhibiting drugs?
Reversible inhibition:
- electrostatic attachment at anionic site
Formation of carbamylesters (reversible)
- done at esteratic site
(Neo, pyrido, physostigmine)
Irreversible inhibition:
- organophosphates combine with the esteratic site to form a stable inactive complex—> lasts for months
(Pesticides, chemical warfare)
T/F At doses greater than usual clinical doses, anticholinesterase drugs have been reported to produce some form of neuromuscular blockade.
True
T/F dementia meds other than Namenda might interact with NMBs.
True
Dementia meds are P.O. AchE inhibitors
______________ is the most important determinant of relative potency.
Affinity
Clinically all AchE inhibitors have the same duration, which is:
T 1/2= 60-120 min
What is the onset of action for edrophonium, neostigmine, and pyridostigmine?
- edrophonium: 1-2 min
- neostigmine: 7-11 min
- pyridostigmine: up to 16 min
What influence does age have with AchE inhibitors?
Neostigmine dose: adult > child > infant
- Edrophonium doses all the same across age
What are muscarinic effects?
More Ach= more rest and digest
- bradycardia
- salivation (risk of aspiration)
- bronchoconstriction
- miosis (delirium since they can’t see)
- hyperperistalsis—> increased risk of PONV- pretty significant
What are nicotinic effects?
Act on neuromuscular junction and autonomic ganglia
___________ and ___________ (but not Edrophonium) produce a marked and prolonged inhibition of plasma cholinesterase.
Neostigmine and pyridostigmine
What are anticholinesterase effects on CV, GI, GU, lungs and eyes?
(All from increasing PSNS)
CV
- bradycardia/bradyarhythmia, AV block, decreased SVR and BP
GI/GU
Increased fluid secretion, increased motility, post op NV (neo)
Lung
- bronchoconstriction, increased airway resistance
Eye
- miosis, inability to focus on near vision, increased IOP
What are clinical uses for anticholinesterase drugs?
- antagonist assisted reversal of NMB
- treatment of CNS effects of certain drugs
- tertiary amines cross the BBB
- treatment of myasthenia gravis
- increase Ach at neuromuscular junction
- treatment of glaucoma
- causes miosis
- post op analgesia
- post op shivering
With antagonist-assisted reversal of NMB, when should the anticholinesterase drug be administered?
During time of spontaneous recovery—> increases availability of Ach at NMJ
- acts pre and post synaptic
What is the onset and duration like for anticholinesterase drugs?
Onset: - Edrophonium = rapid - neostigmine= intermediate - pyridostigmine = delayed Duration: - similar for all—> 55-75 min
Potency depends on:
- NMB being antagonized
- speed of spontaneous recovery
- depth of NMB when reversal is initiated
- end point selected
Why area anticholinesterase drugs mixed with anti cholinergic drugs?
To block muscarinic effects (reversal requires only nicotinic effects)
- administer anti cholinergic with a faster onset than anticholinesterase drug to minimize bradycardia
