Cholinergics & Adrenergics Biology Flashcards
Muscarinic receptors bind to:
ACh, NE
Nicotinic receptors bind to
nicotine, ACh
What time of receptors are Nicotinic receptors? Muscarinic?
Na/K channels - activates and then deactivates. Muscarinic - GPCR - continual effect.
How would you treat cholinergic poisoning?
atropine (muscarinic antagonist)
How would you treat organophosphate poisoning?
pralidoxime
Why would you get paradoxical bradycardia with muscarinic receptor activation?
M receptor activation - get hypotension due to NO-mediated vasodilation, but also get paradoxical bradycardia because there are M receptors on the SA node.
What is the cholinergic syndrome?
DUMBBELSS Diarrhea Urination Miosis Bronchorrea/Bronchoconstriction Bradycardia Emesis Lacrimation Salivation Sweating
What 3 enzymes terminate ACh signaling?
True, Pseudo (blood), and RBC AChE
What are direct M. agonists?
pilocarpine (carbachol), methacoline, and bethanecol
What are indirect M agonists?
AChE inhibitors that increase ACh: Edrophoniium, Neostigmine, Pyridostigmine, Echothiophate
What happens with over-activation of N receptors? (5 things)
1) initial depolarizations, which lead to muscle fasciculations/spasms
2) prolonged occupancy of the receptor with ligand –> paradoxical flaccid paralysis
3) activation of mesolimbic reward system/dopamine secretion
4) net K efflux from muscle –> hyperkalemia + cardiac effects (arrhythmias)
What are short, intermediate, and long-acting cholinesterase inhibitors? What do they do?
potentiates ACh by preventing its degradation
short: edrophonium
Intermediate: neostigmine, physostigmine
long: echothiophate
What happens if you OD on ACh?
1) respiratory suppression due to paralysis of the diaphragm + intercostals (due to nicotinic activation)
* respiratory support is IMPT*
2) increase bronchial secretions/bronchoconstriction (due to nicotinic activation)
What are carbamates?
intermediate acting cholinesterase inhibitors (neostigmine, physostigmine)
What are organophosphates?
long acting cholinesterase inhibitors (echothiophate)
How do you treat organophosphate AChE poisoning? How do you treat carbamate AChE poisoning?
Organophosphate Poisoning: muscarinic blockers (atropine, pralidoxime).
Carbamate poisoning: muscarinic blocker, but NOT NOT PRALIDOXIME (long-acting organophosphate), since it makes it worse.
What is a depolarizing block? Non-depolarizing block?
How would you treat a depolarizing block? Non-depolarizing block?
depolarizing block: inhibitor that binds to the receptor and causes depolarization, followed by receptor desensitization phase that results in receptor inactivation. Reverses with TIME, which allows the ChE to clear the ACh.
nondepolarizing block: inhibitor that binds to the receptor but does not depolarize the motor end plate. Reverses with neostygmine (ChE inhibitor)
An M receptor-antagonist results in these two major effects:
1) blocking parasympathetic transmission
2) sweat glands/CNS activity
What is an inverse agonist?
an agonist that produces an inhibitory effect by shifting the receptor equilibrium from active –> inactive
What is atropine?
muscarinic blocker (M1, M2, M3) - causes UNOPPOSED sympathetic effects: anti-DUMBBELSS
What is ipratropium usually packaged with?
Ipratropium is an inhaled muscarinic blocker and it usually causes bronchodilation.
It is usually packaged with albuterol, which inhibits bronchoconstriction.
What should you worry about for patients who lack plasma ChE? How would you treat these patients if they were accidentally given a loaded dose of succinylcholine?
Succinylcholine (depolarizing nicotinic receptor antagonist) will hang around a lot longer, and will cause flaccid paralysis for a lot longer and will require RESPIRATORY support.
What is tubocuarine? How do you reverse its effects?
its a Nm receptor antagonist. reverse with Neostygmine (AChE inhibitor to increase ACh levels to compete out with the tubocuarine)
What is an example of a non-specific anti-cholinergic?
Botulinum Toxin Type A - prevents docking of ACh vesicles at the cell membrane. Results in flaccid paralysis @ NMJ junctions and atropine effects at M junctions.
What is glaucoma?
production of aqueous fluid»_space;> drainage of aqueous fluid
results in an increase in intraocular pressure, death of retinal-ganglion cells, optic nerve damage
ultimately leads to impaired vision + blindness
How do you treat open/closed angel glaucoma? How do these drug(s) work?
Pilocarpine
Open angle - binds M3 on ciliary sphincter and causes it to contract, which increases tension on the trabecular meshwork, thereby opening the passages for aqueous humor to flow through.
Closed angle - binds to M3 on pupil spincter, causing constriction, which tins the iris, thereby removing the obstruction from the trabecular network and allowing aqueous drainage.
The iris has two types of receptors on these two muscles. What are they and what effects do they cause?
Radial muscle - a1 receptors -> pupil dilation
Circular muscle - M3 receptors -> pupil constriction
What are physiological effects of nicotinic receptor activation?
predominately sympathetic
- tachycardia
- hypertension
- nausea, vomiting, diarrhea, salivation
- urinary incontinence
- cold sweat
- syncope, collapse, unconsciousness
- flaccid paralysis
How is Ne/Epi metabolism different than that of ACh metabolism?
NE/Epi is metabolized by COMT/MAO
ACh is metabolized by AChE
What are Gq receptors?
M1, M3, a1 “odds are queer”
What are Gi receptors?
M2
What are Gs receptors
b1, b2, b3, D1
What are Na/K ion channels?
NN, NM
What are the derivatives of ACh? NE?
ACh: choline + Acetyl CoA
NE: Tyrosine
What is the CVLM? What is the pressor center?
CVLM: depressor center that negatively inhibits the pressor center
Pressor: Nucleus Ambiguus (parasympathetic) and RVLM (sympathetic)
What is the pressor center comprised of?
Ambiguus (parasympathetic) and RVLM (sympathetic)
