Cholinergic Agonists and Antagonists Flashcards
Cholinergic Agonists
- Direct Acting
- 1-Muscurinic receptor
- 2-Nicotinic receptor
- 3 Indirect Acting
- Cholinergic Antagonist
- 4-Muscurinic receptor antagonist
- -Nicotinic receptor antagonists
- -5-Ganglion blockers
- -6-Neuromuscular blockers
- Drugs that act presynaptically
- -7-Inhibitors of ACh Synthesis
- -8-Inhibitors of ACh Storage
- -9-Inhibitors of ACh Release
-1-Acetylcholine, Bethanechol, Carbachol, Methacholine, Muscarine, Arecoline, Pilocarpine
-2-Nicotine
-3 Edrophonium, Carbamates (Physostigmine, Neostigmine, Pyridostigmeni), Organophosphates (Echothiophate, Malathion and Parathion), Nerve Agents (Tabun, Sarin, Soman), Tacrine/Donepezil/rivastigmine/galantamine all for Alzheimers. Pralidoxime to reactivate inhibited acetylcholinesterase before ageing occurs
*4-Atropine, Scopolamine, Synthetic (Ipratropium, Tiotropium, Homatropine, Cyclopentolate and Tropicamide, Benztropine, Trihexyphenidyl, Glycopyrrolate, Tolterodine)
*5- hexamethonium, mecamylamine, trimethaphan
*-6- Tubocurarine (nondepolarizing), Succynilcholine (depolarizing)
7-hemicholinium-3
8-Vesamicol
9-Botulinum Toxin
ACh has 4 primary direct effects on the cardiovascular system
- Vasodilation M3
- Decrease Heart Rate M2
- Decrease in rate of conduction M2
- Decrease in force of contraction M2
Small Dose ACh vs Large Dose ACh
Small=vasodilation=decrease in BP and reflex tachycardia
Large=bradycardia, and decrease in conduction and decrease in BP
ACh effects on various organ systems
Vasculature: vasodilation, release of NO
Eye iris: contraction and miosis
Ciliary muscles: contraction to accommodate to near vision
Salivary and lacrimal: increased secretion
Bronchi: Bronchoconstriction, increased secretions
GI: increased tone, peristaltic activity, secretions, relaxation of sphincters
Bladder: contraction of detrusor muscle, relaxation of sphincter
Sweat glands: diaphoresis
Male repro: Erection
Uterus: variable
Acetylcholine
*no therapeutic application because it affects too much and is quickly hydrolyzed by acetylcholinesterase and a little bit by butyrylcholinesterase.
Binds to Nicotinic and muscurinic receptors
Only real use is to get rapid miosis after delivery of lens in cataracts surgery
Bethanechol
Not hydrolyzed by acetylcholinesterase. Inactivated through hydrolysis by other esterases.
Strong Muscurinic action, no nicotinic
Treatment for a “lazy” bladder.
Carbachol
Both muscarinic and nicotinic agonist.
Not hydrolyzed by acetylcholinesterase.
Used for quick miosis during surgery, and reduces intraocular pressure after cataracts surgery
Methacholine
Mostly Muscarinic
Hydrolyzed slowly by AChesterase (almost totally resistant to hydrolysis by nonspecific cholinesterase)
Used for diagnosis of bronchial airway hyperreactivity in subjects that don’t clinical show asthma
Pilocarpine
Muscarine
Arecoline
P: tertiary amine, partial muscarinic agonist. Uses: Treat Glaucoma. Stimulate Sweating and salivation
M: acts almost exclusively at muscarinic receptors, not clinically used
A: act at both muscarinic and nicotinic receptors, not clinically used.
Nicotine
Tertiary amine, low doses causes ganglionic stimulation by depolarization affecting both SNS and PSNS at same time.
In CVS: increases heart rate and blood pressure
In GI: mainly PSNS, nausea, vomiting, diarrhea, voiding of bladder.
Increase in salivary and bronchial secretions.
At High doses, it causes a ganglionic blockade as a consequence of depolarization. Also causes a neuromuscular blockade.
- Nicotine is highly liposoluble
and absorbs fast via oral mucosa, lungs, GI, Skin and crosses the placenta and is secreted in milk.
USE FOR QUITTING SMOKING
Indirect acting cholinergic agonists
These are cholinesterase inhibitors. They allow endogenous acetylcholine to remain in the synapse
Edrophonium
Binds reversibly. Effects last 2-10 minutes. Quaternary ammonium.
USES: diagnose myasthenia gravis becuase of its short acting duration. Used to reverse neuromuscular block produced by nondepolarizing muscular blockers
Carbamates
form covalent bond with enzyme but can spontaneously hydrolyze within 30 min - 6 hours
Organophosphates
They phosphorylate active sites of the enzyme and this is an extremely strong bond. It may undergo ageing which further strengthens the phosporous enzyme bond. ***Pralidoxine can reverse the bond but only before ageing occurs
Physostigmine
a carbamate, tertiary amine, treatment for overdoses of anticholinergic drugs like atropine. **Do NOT give PHyso to anyone on TCA because it will slow the heart conduction too much.
Adverse Effects: may lead to convulsions at high doses, bradycardia may occur, paralysis of muscles since ACh builds up at NMJ
Neostigmine
carbamate, Quaternary amine, reversal of nondepolarizing neuromuscular blockers after surgery. Used for symptomatic treatment of myasthenia grravis. Prevention and treatment of postoperative distention and urinary retention
Adverse: Salivation, flushing, low BP, Nausea, Abdominal Pain, diarrhea, bronchospasm
Pyridostigmine
Carbamate, quaternary amine, treatment use for myasthenia gravis. *Most common anticholinesterase used for this
Echothiophate
organoP. used for chronic open angle glaucoma, subacute or chronic angle closure glaucoma after iridectomy or where surgery is refused or contraindicated
Malathion and Parathion
M: rapidly metabolized to inactive products in birds and mammals but not insects. safe enough to sell to the public
Parathion: not detoxified effectively in vertebrates so more dangerous. High yield in farmers
Tabun, sarin, soman
very potent synthetic toxic agents
Tacrine, Donepezil, rivistigmine, galantamine
active inhibitors of acetylcholinesterase for treatment of Alzheimers
Atropine
binds competitively to muscarinic receptors. Tertiary amine
Mydriasis, unresponsive to light, cycloplegia (paralyisis of ciliary muscles so you can’t accomadate to near vision), antispasmodic in GI, Decreased gastric motility but HCl secretion not affected, decreased hypermobility of bladder, you block M2 on the heart causing tachycardia, secretions are inhibited for saliva, sweat, and tears.
t0.5=4hrs, eliminated in urine and metabolized in liver.
USES: reduce airway secretions for surgery, to increase heart rate or decrease AV vlock, antidoite to overdose on cholinergic drugs, antidote to mushroom poisoning, alleviates muscarinic side effects of anticholinesterase drugs like neostigmine
Scopolamine
produces peripheral effects similar to atropine. Greater actions on CNS and longer duration. One of most effective drugs for motion sickness. Unusual effect: blocks short term memory, produces sedation unlike atropine. At high doses can cause excitation.
USES: for mydriasis and cyclopegia in diagnostic procedures, prevention of nausea
Ipratropium and Tiotropium
inhalation drugs that treat COPD and Asthma
muscarinic antagonists
