Muscarinic Agonist Flashcards
What is the rate limiting step of Cholinergic Neurotransmission?
Choline Acetyltransferase
-from choline and acetyl CoA
Which enzyme degrades ACh?
Acetylcholinesterase (AChE)
True or False: M4 are autoreceptors. (Located on or close to the axon terminal)
True
-ACh released from parasympathetic neurons interacts with M4 receptors to inhibit ACh release.
True or False: ACh influences the release of NE from sympathetic neurons by acting on presynaptic M4 receptors. This is known as an Heteroreceptor.
True
Why is ACh’s penetration to the CNS is limited when administered systemically?
The presence of butyrylcholinesterase in the blood degrades ACh. This also limits the targets it reaches.
Which organs are the Muscarinic receptors found?
M1-CNS
M2-Cardiovascular system (negative chrono and ino; vasodilation by M3)
M3-Periphery (Gq)
-Constriction and secretion
What should we know about nitric oxide?
Produces relaxation in the endothelial cell and contraction in the smooth muscle cell.
Methacoline
-Hydrolyzed by AChE
-Lacks Nicotinic actions
-Poor absorption, does not cross BBB
-For asthma and COPD diagnosis
-Side effect: hypotension and Bradycardia
Carbachol
-Not hydrolyzed by AChE
-Muscarinic and Nicotinic actions
-Can cause release of epinephrine from adrenal medulla
-Treat glaucoma and cataract surgery (rarely)
Bethanechol
-Not hydrolyzed by AChE
-Lacks Nicotinic actions
-Treats Non-obstructive urinary retention and paralytic ileus
Contraindications of Choline esters
-Asthma
-Hyperthyroidism
-Coronary insufficiency
-Acid-peptic disease
Parasympathetic activation in ventricular fibrillation in the setting of cardiac ischemia
Antiarrhythmic
Pilocarpine
-Cross BBB
-Hydrolysis by AChE
-Only Muscarinic actions
-less potent than ACh
-Treat xerostomia (promotes tears)
-Drug of choice in emergencies to reduce intraocular pressure.
Which drug has been shown to have less side effects (sweating) than pilocarpine in patients with sjogrens?
Cevimeline
Reversible AChE inhibitors
-Hydrolyzed by AChE but much more slowly than ACh,
-Contains Edrophonium and it’s a competitive inhibitor of AChE.
Which compounds are irreversible AChE inhibitors?
Organophosphate
-Enhanced by aging
Aging of Organophosphate
-the loss of one of the alkyl groups in the phosphate group. Cause inactivation of AChE.
What can be given before aging to break phosphorus-enzyme bond?
Pralidoxime
What happens to neuromuscular junctions at low therapeutic concentrations?
Increase strength of contraction
What happens to neuromuscular junctions at High therapeutic concentrations?
Accumulation of ACh causing paralysis.
Myasthenia Gravis
Enfermedad autoinmune que enlaza anticuerpos a receptores Nicotinicos.
Causa:
-ptosis (no levanta párpado)
-diplopia (tiene visión doble)
-Problemas para hablar y tragar
Diagnóstico: Edrophonium test
Medicamentos para Myasthenia Gravis
Pyridostigmine, Physostigmine y Neostigmine
Edrophonium
Short-acting AChE inhibitor
-Diagnosis of Myasthenia Gravis
Neostigmine
For Atony and Myasthenia gravis
-Cannot cross BBB
It’s like Pyridostigmine but this last one is longer acting and for chronic management of Myasthenia Gravis.
Which two Acetylcholine Release Modulators are K Channel Antagonist?
Amifampridine and 4-aminopyridine
Physiotigmine
Intermediate-acting AChE Inhibitor
-to treat glaucoma (stimulates CNS) but pilocarpine is more effective
-treat Anticholinergic overdose (antídoto)
-Overdose can cause Cholinergic syndrome (DUMBELS)
-Its metabolite (eseroline) acts as an opioid agonist.
What are AChE inhibitors that treat Alzheimer?
Tacrine
Donepezil
Rivastigmine
Galantamine
Indirect-acting cholinergic agonist Anticholinesterases (Irreversible)
Sarin, Soman, and Tabun
-Many of organophosphates are highly lipid-soluble liquids and is distributed to all the body excepts Echothiophate
Echothiophate
Action: cholinergic stimulation, paralysis of motor function
-To treat glaucoma provoking intense miosis
-Atropine can reverse its effect
Parathion and Malathion
Both are prodrugs use as insetcides but parathion is more dangerous.
Organophosphates Antidotes
-Atropine is an mAChR antagonist
-Reactivators: separate inhibitor from AChE (Dephosphorylate)
-Pralidozime (PAM)
Pralidoxime (PAM)
Its must be used immediately, no more than 36 hours of exposure
Can reactivate inhibited Acetylcholinesterase before aging except in the CNS since it does not cross it.
