2. Cholinergic Agonists and Muscarinic Antagonists Flashcards
What is the primary NT innervating SKM?
ACh
Which muscarinic receptor subtypes are excitatory? what is there signaling?
M1, 3, 5
- Inc IP3
- Inc Ca2+
Which muscarinic receptor subtypes are inhibitory? What is their signaling?
M2, 4
- Dec cAMP
- Inc K+ conductance
- Also function as auto-receptors, that can be located pre-synaptically and self-regulate ACh release
What are the muscarinic agonist effects on the eye?
-
Constriction of pupil
- Focusing for near vision
- Allows for drainage of vitreous humor, helping to reduce intra-ocular pressure
- Tx for glaucoma - pilocarpine
What are the muscarinic agonist effects on the heart?
-
Decreased:
- HR
- Contractility
- Conduction Rate
- Impact has variability b/c may be compensated by SNS - baroreceptors activation of the SNS to regulate BP
What are the muscarinic agonist effects on the vascular smooth muscle?
- Blood Vessel Dilation
- Stimulation of Secretory Glands
How is vascular smooth muscle dilated via a muscarinic agonist?
-
Release of NO through direct activation of local M3 receptors on the endothelium, which leads to:
- Increased cGMP
- Reduces intracellular Ca2
- Which reduces phosphorylation of myosin
- Allows muscles to relax
What are the muscarinic agonist effects on the urinary tract? What are they used to treat?
-
Relaxes bladder:
- Constricts detrusor
- Relaxes trigone
- Relaxes sphincter muscle
- Tx for Urinary Retention - bethanecol
What are the muscarinic agonist effects on the secretory glands in the bronchus? What are they used to tx?
- Bronchoconstriction and increased mucous secretions
- Used to test for Asthma (hyperactive airway), by giving the pt methacholine to stimulate bronchoconstriction
What can be used as bronchodilators?
Anti-cholinergics
What are the muscarinic agonist effects on intestinal function? What are they used to tx?
- Increased motility and secretions
- Decreased sphincter tone
- Tx of cessation of intestinal function that can occur post-op
What do you use to tx xerostomia?
muscarinic agonist
cevimeline
What pts are at an increased risk for adverse effects from muscarinic receptor activation?
- Asthma
- CVD
- Peptic ulcers
Which classification of AChE Inhibitors/Anticholinesterases has therapeutic value?
Reversible AChE Inhibitors
-
neostigmine
- Tx of myasthenia gravis, reversal of nondepolarizing muscle relaxants
-
physostygmine
- Tx of gluacoma
What are Irreversible AChE Inhibitors used for?
Insecticides - organophosphates
Binds to and damages AChE
Which receptor does Acetylcholine have a greater affinity for?
muscarinic
How does atropine treat insecticide poisoning from organophosphates?
- It is a muscarinic receptor antagonist that alleviates CNS and parasympathetic stimulation
- Solves immediate problem
- But have to wait 2wks for AChE to reload
What is another drug besides atropine that is used to treat insecticide poisoning from organophosphates? How does it work?
pralidoxime
- Can bind to site within AChE
- Interacts with phosphoryl group left by organophosphate
- Can sequester phophoryl group and reactivate AChE
What are the therapuetic cholinergic agonists used to tx Glaucoma?
- Beta blockers
- Prostaglandins
What are the therapuetic cholinergic agonists used to tx xerostomia?
Direct Agonists
- Pilocarpine
- Cevimeline
What are the therapuetic cholinergic agonists used to tx reversal of neuromuscular block?
Indirect agonists
- Competitive inhibition of nicotinic receptors
What are the therapuetic cholinergic agonists used to tx myasthenia gravis (AI disorder that attacks ACh receptors)?
Indirect agonists
- Inc amounts of ACh within signaling to help tx
What are the therapuetic cholinergic agonists used to tx atropine poisoning?
Physostigmine
- CNS availability (indirect agonists)
What are the therapuetic cholinergic agonists used to tx paralytic ileus?
Bethanecol
- Direct agonist
