Section 2d Cholinergic Agonists Flashcards
Where is M2 found? How does it work?
Heart smooth muscle, hyperpolarization (decrease AC & increase K+ opening)
Where is M3 found? How does it work?
Smooth muscle (like GI), Bladder, Exocrine gland; contraction (increase PLC and Ca)
Where is Nm found? How does it work?
skeletal muscle–> End-plate depolarization AND NMJ –> skeletal muscle contraction (open Na/K channels)
Where is Nn found? How does it work?
anatomic ganglia –> depolarization and firing of postganglionic neurons AND adrenal medulla –> secretion of catecholamines (opening of Na/K channels)
What is the effect of a muscarinic agonist on M2? (Heart)
cardiac slowing and decrease in cardiac output, and vasodilation (NO mediated effect)
What is the effect of muscarinic agonist on M3? (GI)
smooth muscle (other than vascular smooth muscle) contracts and peristaltic activity increased (digestion)
What is the effect of muscarinic agonist on M3? (Eye)
contraction of ciliary muscle (effects focus), pupil contraction (miosis), and lowers intraocular pressure in acute glaucoma
What does the NMJ consist of?
motor neuron, motor endplate, synaptic cleft/junctional gap
What is found on the postsynaptic membrane in the synaptic cleft of the NMJ?
ACh receptors adn Acetylcholineesterases
What help ACh release in he NMJ?
Ca2+ and ACh binding to presynaptic neuron (+ feedback loop)
The extent of depolarization in nicotinic receptor end-plate depolarization is dependent upon what?
quantity of ACh
What is it called when a small amount of ACh causes a slight depolarization in the end-plate?
miniature end-plate potential (MEPP)
What is required for muscle contraction?
accumulation of a sufficient concentration of ACh at the motor end plate to depolarize beyond -55mV
What is the major function of indirect acting cholinergic agonists?
Act on acetylcholinesterase
What are direct-acting cholinergic agonists also known as
parasympathomimetics (choline esters & naturally occurring alkaloids)
Which is more specific for Cholinergic receptors, parasympathomimetics or ACh (itself)?
the drugs
What are the 4 major Direct acting cholinergic agonists?
Choline esters: Methacholine, carbachol, bethanechol
Alkaloids: Pilocarpine
Of the Parasympathomimetics (choline esters and alkaloids) which is more like ACh and which for Muscarine?
Acetylcholine-like = choline esters Muscarine-like = alkaloids
How is strength (dose) of ACh related to cardiac effects?
non-specific; at low doses it decreases heart rate and BP but BP is increased with super high doses
Of the choline ester Cholinergic agonists, which one has effects of muscarinic and nicotinic receptors?
Carbachol
What choline ester Cholinergic agonist has strong muscarinic activity and acts on smooth muscle of the bladder and GI?
Bethanechol
What is Bethanechol used for?
urinary retention, glaucoma (causes pupillary contraction)
What Cholinergic agonist is used as a mitotic agent to treat glaucoma?
Carbachol
What are symptoms of Sjogren’s syndrome (dry mouth and lack of tears) treated with?
Pilocarpine
What is the drug of choice in the emergency of lowering IOP in glaucoma?
Pilocarpine
What is an adverse effect of Pilocarpine?
CNS disturbances
Suxamethonium chloride or succinylcholine has high affinity for what receptor?
nicotinic receptor - used as a surgical anesthetic (used only for short durations
Prolonged use of succinylcholine can cause what?
life threatening electrolyte imbalance
What are the adverse effects of succinylcholine?
cardiac arrhythmia, respiratory depression, muscle rigidity, and raised IOP
What are the 2 types of cholinesterases? Do most drug prefer to block one over the other?
Acetylcholinesterase (AChE)
Butyrylcholinesterase (BuChE)
Both are blocked pretty equally
Besides the clinical applications, what else are AChE inhibitors used for? (2)
- insecticides
2. chemical warfare agents (nerve gas)
Where does AChE inhibitors bind on AChE?
active site
What are the 3 chemical classes of AChE inhibtors?
- Simple alcohols (Edrophonium)
- Carbamic acid esters (Neostigmine and Physostigmine)
- Organophosphates (Isoflurophate
What is Mysthenia Gravis?
autoantibodies against nicotinic receptors –> induce nicotinic receptor internalization –>thus no sodium enters via the nicotinic receptors
What is Lambert-Eaton Myasthenic Syndrome (LEMS)
autoantibodies against Ca2+ channels –> Ca2+ entry and ACh release are lessened
Edrophonium: reversible/irreversible? Long acting/short acting? Used for? chemical type?
- Reversible AChE inhibitor
- Short acting
- Used for the DIAGNOSIS of myasthenia gravis
- simple alcohol
What is the antidote to Edrophonium?
atropine
What can be used as an antidote to tubocurarine?
Edrophonium, Neostigmine
Physostigmine: chemical type? can it pass BBB? Uses? Adverse effects?
- nitrogenous carbamic acid ester
- can cross BBB
- increase intestinal and bladder motility, produces miosis thus lowering IOP, treatment of anticholinergic overdose
- bradycardia (fall in Cardiac output), paralysis of skeletal muscle <– usually seen more with higher doses
Neostigmine: chemical type? pass BBB? Used for? Adverse effects?
- synthetic carbamic acid ester
- does NOT pass BBB
- used for TREATMENT of myasthenia gravis
- salivation, decreased BP, nausea, ab pain, diarrhea, bronchospasm
What makes irreversible anticholinesterase drugs reversible? Can in pass BBB? How does it work?
Pralidoxime (PAM), NO, displaces phosphate group in the inactive enzyme and when it loses the Alkyl group that is called aging
What 2 drugs are used for chronic management of myasthenia gravis? (AChE inhibitors)
- Pyidostigmine
2. Ambenonium
What is Demecarium used for?
treat chronic open-angle glaucoma
Echothiophate: chemical type? reversible/irreversible? Antidote? Uses? Adverse effects
- Organophosphate
- Irreversible
- atropine
- used directly in the eye for chronic treatment of open-angle glaucoma - effect may last up to a week
- potential cataracts, limit the use due to long duration
