Cholinergic Agonists and Antagonists Flashcards
The muscarinic receptor is what kind of receptor?
GPCR
The nicotinic receptor is what kind of receptor?
Ligand gated ion channel
Generally, what functions does the parasympathetic NS have on the…eye, heart, bronchioles, GI tract, bladder?
Pupillary constriction Decreased chronotropy and inotropy Bronchiole constriction Increased GI motility Stimulate bladder emptying
What does the M1 receptor do?
Activates myenteric plexus to stimulate peristalsis in gut
What does the M2 receptor do?
Decreases HR. It hyperpolarizes SA node pacemaker cells by opening K+ channels and allowing K+ to flow out of the cell.
What does the M3 receptor do?
Contracts ciliary muscle in the eye to allow for accomodation.
Bronchiole smooth muscle- leads to bronchoconstriction.
Activates bladder detrusor muscle to cause urination.
Stimulates secretions of GI tract, sweat glands, tear glands, and salivary glands.
How does the nicotinic receptor function? What binds the receptor and what does that cause?
Ligand gated ion channel. Two Ach molecules bind the receptor, inducing a conformational change to allow Na+ to flow through and depolarize the membrane.
Name the two kinds of nicotinic receptors and where they are located.
Nm = located in skeletal muscle; promotes skeletal muscle contraction
Nn = located on neurons in the CNS, parasympathetic and sympathetic ganglia
What is the one medical use for nicotine?
Smoking cessation!
Transdermal patch to help relieve smoking addiction
Nicotine is a selective agonist for what receptor?
Nn receptor
How is Succinylcholine used clinically?
Muscle relaxant
How does succinylcholine produce its physiological effects?
Succinylcholine is an Nm agonist. It binds the Nm receptors and activates them constitutively, preventing propagation of the action potential. Prolonged depolarization of the membrane prevents Na+ channels from leaving their inactive state, preventing the propagation of the action potential.
Will acetylcholine cross the BBB? Why or why not?
No!
It is positively charged.
Is acetylcholine useful medicinally?
Not really. Cholinesterases will degrade Ach very quickly.
Methacholine acts primarily at what kind of receptors?
Muscarinic
How is methacholine used clinically?
Used in the diagnosis of asthma. If a patient is given low doses of methacholine and experiences severe bronchoconstriction, then it is determined that he/she has asthma.
Methacholine toxicity
Bronchiole constriction
Contraindication for methacholine
Patient is taking a beta-blocker
Carbachol has action at what receptors?
Nicotinic and muscarinic
Where is carbachol used exclusively? Why?
In the eye! It can reduce pressure from ocular surgery and glaucoma. It is a topical miotic agent.
What kind of receptors does bethanechol bind? What is special about bethanechol?
Binds muscarinic receptors. It is resistant to degradation by cholinesterases, so it has a long half life.
How is bethanechol used clinically?
Used in cases of post-op urinary retention or neurogenic bladder atony. It helps patients urinate!
Toxicity of bethanechol?
Bradycardia
Bronchoconstriction
Contraindications of bethanechol?
Asthma
Peptic ulcers (can stimulate secretions in the lungs and gut)
Bradycardia
Pilocarpine is a…
Nonselective muscarinic receptor agonist
Indications of pilocarpine
Dry mouth in patients undergoing head/neck radiation
Sjogren’s Syndrome- antibodies attacking salivary glands
Glaucoma
Toxicity of pilocarpine
Excess muscarinic activation can promote heart block due to high number of muscarinic receptors in the AV node
What are the two kinds of cholinesterases? Where are they located?
Acetylcholinesterase- commonly located at the NMJ near nicotinic receptors.
Butrylcholinesterase- located in the plasma
What do indirectly acting cholinomimetics do?
They inhibit cholinesterases, thereby increasing the half life of Ach
Neostigmine Indications
- Myasthenia gravis
- Reversal of non-depolarizing neuromuscular blockade
Neostigmine Physiological effects
Increase activation of Nm receptors by increasing Ach concentration at the NMJ. Helps alleviate muscle weakness. Has some direct effects in activating the nicotinic receptor at the NMJ
Neostigmine Toxicity
Muscarinic and Nicotinic excess
