CHAPTER 4: INDIRECT ACTING CHOLINERGIC AGONISTS Flashcards
how do Indirect Acting Cholinergic agonists work?
they act on the ENZYME
what enzyme does indirect chol agonist act on
cholinesterases that act indirectly on PNS
indirect chol agonists- response in which receptors
muscarinic and nicotinic in ANS and brain
what are the indirect-acting cholinergic REVERSIBLE agonists
Edrophonium, physostigmine, neostigmine, donepezil, rivastigmine, galantamine
indirect chol agonist- Edrophonium (reversible)
- what does it bind to
- duration of action
quarternary ammonium comound that binds reversibly to the active site of AChE, prevents hydrolysis of ACh
-RAPID duration of actions (10-20 mins)
edrophonium- therapeutic action
rapid inc muscle strength
edrophonium- therapeutic uses/indications
diagnose myasthenia gravis
edrophonium- adverse effects
-what drug counteracts?
cholinergic crisis with excess of the drug, then you need withdrawal and use ATROPINE TO COUNTERACT
what is Myasthenia Gravis?
chronic muscular disease caused by a defect in neuromuscular transmission
-autoimmune disease, so patients make antibodies to ACh receptions, gradually destroying them
myasthenia gravis symptoms
-myasthenic crises
progressive weakness, lack of muscle control
myasthenic crisis vs. cholinergic crisis
myasthenic: extreme muscle weakness, difficult respiration, NEED INC DOSE
cholinergic: progressive muscle weakness, difficult respiration while ACh accumulates at receptors, reduced impulse transmission, WITHDRAWAL OF DRUG NEEDED
edrophonium for crisises
used as a diagnostic agent to treat or cause adverse effects
edrophonium in myasthenic crisis
patient improves immediately after injection
edrophonium in cholinergic crisis
patient gets WORSE, drug toxicity (cholinergic crisis), atropine alleviates parasymp reactions to this cholinergic drug
Indirect acting reversible- Physostigmine
-action
-duration of action
binds reversibly to AChE prevent Ach degradation
-duration of action 2-4 HOURS
-can enter CNS
tertiary amine (not charged)
Physostigmine- therapeutic effects
potential cholinergic activity throughout body
- miosis
-contraction of visceral smooth muscle
-skeletal muscle twitching
Physostigmine- therapeutic uses/indications
optho for glaucoma
treating overdose of anticholinergic drugs
Physostigmine- adverse effects
convulsions, bradycardia, fall in cardiac output
Indirect acting chol ago reversible- Neostigmine
-action
duration of action
-bind to AChE stop degrading ACh
-duration of action 30min-2hours
-synthetic and CHARGED compound (N+)
Neostigmine- therapeutic effects
effect of skeletal muscle greater than physostigmine
Neostigmine- therapeutic uses/indications
antidote for tubocurarine (NMB)
treats myasthenia gravis
Neostigmine- adverse effects
general cholinergic stimulation (salivation, flushing, nausea, diarrhea, bronchospasm)
NO CNS SIDE EFFECTS (bc its charged, doesn’t cross BBB)
Indirect chol ago reversible- Donepezil, Rivastigmine, Galantamine
deficiency of cholinergic neuron in ALZHEIMER’S DISEASE
-anticholinesterases as remedies for loss of cognitive functions
-delay of progression
what are the IRREVERSIBLE indirect-acting cholinergic agonists?
echothiophate and pralidoxime
indirect cholinergic agonist irreversible- Echothiophate
-purpose
-duration of action
phosphate compound that INACTIVATES AChE permanently when covalently bonded
-duration of action 1 WEEK
echothiophate- therapeutic actions
cholinergic stimulation, paralysis of motor function, convulsions
-MIOSIS
echothiophate- therapeutic use/indication
open-angle glaucoma
echothiophate- adverse effects
risk of causing cataracts limit use
nerve gas is
an irreversible acetylcholinesterase inhibitor (echothiophate)
nerve gas causes
muscle paralysis, stop breathing, death
antidote for nerve gas- irreversible indirect-acting cholinergic agonists
pralidoxime
pralidoxime also used with…
atropine since it can cross the BBB, its the antidote for CNS
