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
What are the therapuetic cholinergic agonists used to tx bladder atony?
Bethanecol
- Direct agonist
What is used to tx Alzheimer type dementias?
therapuetic cholinergic agonists
What organs does atropine have a larger effect on?
- Lungs
- GI
- Heart
What organs does scopolamine have a larger effect on?
- Eye
- Secretory Glands
- CNS
What are the effects of muscarinic antagonists on the eye?
- Paralysis of accommdation
- Intraocular pressure is only impacted in narrow-angle glaucoma
What are the effects of low dose muscarinic antagonists on the cardiovascular system?
mild bradycardia
What are the effects of higher dose muscarinic antagonists on the cardiovascular system?
tachycardia
What are the effects of muscarinic antagonists on the Genitourinary tract?
urinary retention
What are the effects of muscarinic antagonists on body temp?
Inhibition of sweating can cause increase in body temp
What muscarinic antagonist is more effective at the medulla and higher cerebral centers?
Scopolamine
- Can cause:
- Drowsiness, Sedation
- Euphoria
- Amnesia, Delirium, Hallucinations
What is Parkinson’s Disease related to in the CNS?
Loss of balance between cholinergic and dopamine signaling in the striatum
What is motion sickness related to in the CNS?
Acetylcholine acts as a neuromodulator in the vestibular system increasing responsiveness
What is an adverse affect of muscarinic antagonists in children treated with physostygmine?
Atropine poisoning
What is an adverse affect of muscarinic antagonists for pts with narrow-angle glaucoma?
increased intraocular pressure
What is an adverse affect of muscarinic antagonists in pts with prostatic hypertrophy?
urinary retention
Why do synthetic quaternary ammonia muscarinic antagonists have no CNS effects?
Does not cross BBB
