30: Drug Action on Muscarinic Receptors Flashcards
What is a muscarinic receptor?
A type of acetylcholine receptor
Describe the subtypes of muscarinic receptors.
M1, M3, and M5 are coupled with trimeric Gq protein –> stimulatory function.
M2 and M4 are coupled with trimeric Gi protein –> inhibitory function.
Describe the structure of muscarinic receptors.
7 transmembrane domains (TM1-7) are connected by intracellular or extracellular loops.
Explain the tissue distribution and physiological functions of M1 muscarinic receptors.
- autonomic ganglia - increase excitatory postsynaptic potential
- CNS - increase excitation in neurons
- Salivary glands - increase secretion
- stomach glands - increase secretion of gastric acid
Explain the tissue distribution and physiological functions of M2 muscarinic receptors.
- heart - slow heart rate, reduce contractile forces of atrial muscle, and reduce conduction velocity of AV node
- presynaptic terminal - inhibit acetylcholine release
Explain the tissue distribution and physiological functions of M3 muscarinic receptors.
- blood vessels - increase vasodilation
- lungs - cause bronchoconstriction
- bladder - increase contraction
- vascular endothelium - increase intracellular calcium –> vasoconstriction
- endocrine/exocrine glands - increase secretions
- eye - increase iris sphincter muscle contraction
- pancreas - increase insulin secretion
Explain the tissue distribution and physiological functions of M4 muscarinic receptors.
In CNS - decrease locomotion (movement from one place to another)
Explain the tissue distribution and physiological functions of M5 muscarinic receptors.
Unclear
What are the two types of muscarinic receptor agonists?
Choline esters and cholinomimetic alkaloids
Name choline ester drugs that act as agonists of muscarinic receptors.
- acetylcholine
- methacholine
- carbachol
- bethanechol
have sensitivity to acetylcholinesterase
Name cholinomimetic alkaloids that act as agonists of muscarinic receptors.
- muscarine
- pilocarpine
- oxotremorine
- xanomeline
Describe the different selectivities of muscarinic receptor agonists.
Explain Methacholine’s drug action and pharmacological use.
Drug action: M1-5
* methacholine acts as a non-selective muscarinic receptor agonist to stimulate the PNS.
Use: Bronchial challenge test
* Methacholine causes bronchoconstriction and people with pre-existing airway hyperreactivity will react with lower doses of drug.
Explain Carbachol’s drug action and pharmacological use.
Drug action: M1-5, Nn, Nm
* parasympathomimetic that stimulates both nicotinic and muscarinic receptors
* can stimulate and depress cardiovascular and GI systems (bc of its ganglion-stimulating activity)
* can cause release of epinephrine from the adrenal medulla by its nicotinic action
* in the eye - can mimic ACh –> constant contraction of ciliary muscle (miosis)
Use: miotic agent to treat glaucoma
* causes pupillary contraction and a decrease in intraocular pressure
* also can be used to stimulate bladder emptying
Explain Bethanechol’s drug action and pharmacological use.
Drug action: M1-5
* stimulates muscarinic receptors –> causes increased intestinal motility and tone.
* stimulates bladder muscle –> produce urination
Use: treats urinary retention by stimulating the atonic bladder
Explain Pilocarpine’s drug action and pharmacological use.
Drug actions: acts on a subtype of muscarinic receptors - M3
Use:
* glaucoma - causing muscle contraction –> pupil constriction (miosis)
* dry mouth - stimulating the secretion of large amounts of saliva and sweat
* diagnose cystic fibrosis - stimulating sweat glands to measure the concentration of chloride and sodium that is excreted in sweat.
Define muscarinic antagonist.
An agent that has high binding affinity for the muscarinic receptors but has no intrinsic activity.
* competes with ACh to occupy receptors
Name some anatagonists for muscarinic receptors.
- atropine
- scopolamine
- ipratropium
- tiotropium
- tropicamide
- cyclopentolate
Most muscarinic antagonists have no selectivity for subtypes. Which antagonists have selectivity? For which subtypes?
- Pirenzepine - M1
- Gallamine - M2
- Darifenacin - M3
Describe the therapeutic application of muscarinic receptors + antagonists on the eye.
Organ: iris circular muscle
Muscarinic receptor effects: contracts
Antagonist effects: relaxes
Organ: ciliary muscle
muscarinic receptor: contracts
anatagonist effects: relaxes
* therapeutic indication:* mydratic (makes eye dilate)
Describe the therapeutic application of muscarinic receptors + antagonists on the heart.
Organ: sinoatrial node OR atrial contractility
Muscarinic receptor effects: decelerates
Antagonist effects: accelerates
Therapeutic indication: bradycardia
Describe the therapeutic application of muscarinic receptors + antagonists on the GI tract.
Organ: smooth muscle
Muscarinic receptor effects: contracts
Antagonist effects: relaxes
Therapeutic indication: GI antispasmodic
Organ: secretions
Muscarinic receptor effects: increases
Antagonist effects: decreases
Organ: sphincters
Muscarinic receptor effects: relaxes
Antagonist effects: contracts
Describe the therapeutic application of muscarinic receptors + antagonists on the lungs.
Organ: smooth muscle
Muscarinic receptor effects: contracts
Antagonist effects: relaxes
Therapeutic indication: asthma and allergic rhinitis
Describe the therapeutic application of muscarinic receptors + antagonists on the bladder.
Organ: smooth muscle
muscarinic receptor effects: contracts
antagonist effects: relaxes
therapeutic indication: overactive bladder
