Lecture 18 Flashcards
Where, by what enzyme, and from what components is acetycholine (ACh) synthesized?
Sythensized in presynaptic nerve terminals by choline acetyl transferase (CAT) using choline and acetylene-CoA.
What are the 2 main ACh receptors (AChR) and how are they different from each other?
Nicotinic ACh receptor and Muscarinic ACh receptor.
NAChR are found in all postganglionic cells of the parasympathetic and sympathetic nervous system but muscarinic ACh receptors are only found in target tissues of the PNS
How is ACh action terminated normally after it has been released into the synaptic cleft?
It is degraded by Acetylcholine esterase enzyme.
In what way to M1, M2, and M3 actions differ?
M1 and M3 are excitatory receptors located in smooth muscle and glands causing parasympathetic actions of smooth muscle constriction and glandular secretions. M2 is an inhibitory receptor located in the heart. Activation of M2 receptors causes inhibitory actions of the PNS, primarily inducing bradycardia.
What has muscarinic receptors, but no PNS innervation, and that muscarinic agonists will affect, mimicking the PNS?
Blood vessels
Where are muscarinic AChR located?
Smooth muscle (viscera), glands, cardiac muscle, sweat glands
Explain why nicotinic and muscarinic agonists have different effects, but they both act like ACh?
Because they activate the nACh and mACh receptors respectively. They muscarinic agonists are going to only activate parasympathetic nervous system whereas activation of nicotinic receptors is going to activate both parasympathetic and sympathetic response as well as cholinergic responses at the NMJ.
How will muscarinic agonists affect blood vessels?
At high enough doses, muscarinic agonists can bind to mACHR on blood vessels to induce a PNS effect of vasodilation to viscera and skin.
Why will nicotinic receptor agonists and antagonists have complex effects?
Because they will stimulate both parasympathetic and sympathetic effects since all postganglionic cells (PNS and SNS and NMJ) have nAChR
What are muscarinic receptor antagonist effects dependent on?
The parasympathetic tone of the tissue to begin with (no tone, no antagonistic effects).
Why is it important to know what there are drugs selective for muscle versus neuronal nicotinic AChR?
So you can use the correct drug without inducing unnecessary side effects.
What are- in broad terms- 4 effects of ACh esterase inhibitors?
- Enhance muscarinic (parasympathetic) effects
- Enhance ACh concentrations at the NMJ
- CNS effects
- Combo of nicotinic and muscarinic effects
Define Cholinergic:
Induces acetycholine-like effects across the board
Define Parasympathomimetic:
ACh-like effect on parasympathetic targets
Define muscarinic:
Induces muscarinic ACh effects by targeting muscarinic receptors. (Parasympathetic at glands, smooth muscle, heart)
Define Nicotinic:
Causes PNS and SNS effects by targeting nACh receptors.
Where does the name “Muscarine” come from?
A mushroom (Toadstool)- amanita muscaria
What are the 4 major actions of muscarinic AChR agonists (on nonvascular smooth muscle)?
Bronchoconstriction
Urinary muscle constriction
Urinary sphincter relaxation
Increased GI motility (constriction)
Give 4 examples of muscarinic agonists effects on exocrine glands.
- Lacrimation
- Salivation
- Sweating
- Bronchial secretion
Explain DUMBSLED!
These are the results of parasympathetic stimulation: D-iarrhia U-rination M-iosis B-radychardia S-wetting L-acrimation E-mesis D-yspnea
What are 3 cardiac muscarinic agonist effects and explain them (why these effects?)
- Bradycardia leading to reduced cardiac output (M2 inhibitory receptor on cardiac tissue)
- Reduced blood pressure (vasodilation and reduced cardiac output cause reduction in blood pressure)
- Vasodilation (mAChR activation on blood vessels induced NO release. NO is a potent vasodilator)
Provide 3 clinical uses of muscarinic agonist drugs (with example of drug).
- Bethanechol- treat bladder atony by increasing constriction of smooth mm in bladder.
- Pilocarpine- reduce intraocular pressure for glaucoma patients by increasing ocular drainage.
- Carbachol- treat GI atony by increasing intestinal motility.
What are 5 common adverse effects of muscarinic agonist drugs?
- Constriction of the pupil, lack of accomodation for vision
- Excess inhibition of the heart (excessive bradycardia)
- Excess vasodilation causing hypotension
- Diarrhea
- Bronchoconstriction and excess bronchial secretions leading to breathing difficulties
Which are 6 contraindication for the administration of muscarinic agonists?
Pneumonia Asthmatics/bronchoconstriction Urinary blockage Intestinal blockage Arrhythmia Pregnancy
