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Flashcards in Autonomics II Deck (33):

What are the two types of nicotinic acetylcholine receptors? What kinds of receptors are they? Structure?

NMJ type and neuronal type
ligand-gated ion channels with 2 or more transmembrane subunits. nonselective cation pore to yield depolarization


What are our three main therapeutic interests in the nicotinic acetylcholine receptor?

1. muscle relaxation for surgical procedures
2. target of poisoning by AChE blockers
3. etiology/treatment of myasthenia gravis


What is the structure of the nicotinic ACh receptor at the NMJ>

5 subunits, 4 of which are unique (2 alpha subunits)


MOA of Tubocurarine. cure for toxicity?

competative antagonist nAChR.
overcome toxicity with ACh esterase inhibitors


What is the use of tubocurarine and side effects?

use: muscle relaxation for surger
hypotension,(generalized histamine release), resp. muscle paralysis


What is the MOA of succinylcholine?

atagonists that are partial agonists at the NMJ. they are noncompetitive, depolarizing blockers. they lead to transient activation of nAChR, followed by prlonged desensitization bc they dissociate quite slowly from the receptor


What are differences in the treatment of overdose with tubocurarine vs. succinylcholine?

tubocurarine OD treatable with AChE inhibitor, succinylcholine NOT- AChE inhibitor would just further desensitize the receptors


When do you use a succinylcholine?

rapid onset short duration muscle relaxation


What is the structure of the ganglionic type nAChR?

many different subtypes with subunits that are either alpha or non-alpha.


What is the MOA of hexamethonium? Main use?

selective for neuronal type nAChR
competitive at the nACHR to decr. sympathetic and parasympathetic input to target tissues.
mostly used in research


What is the structure of the muscirinic AChR?

7 membrane-spanning G-protein-coupled receptor superfamily. 5 types now identified in different tissues.


What do m1, m3, m5 AChRs do? (mAChRs)

activate phospholipase C and incr. PI (phosphoinestitase?) turnover --> activation of protein kinase C and release of intracellular Ca.


What do m2 and m4 do? (AChRs)

inhibity adenylate cylcase; decr. cAMP


Describe the characteristics of mos muscirinic ACh receptor agonist drugs.Exception? Differences between the drugs?

typically synthetic ACh analogs. differ in sensitivity to just muscirinic (vs. nicotinic) receptors and in metab by AChE. Positive amine gropu prevents passage to CNS. expecption is pilocarpine- naturally-ocurring uncharged compound.


What are some effects of mAChR agonists?

decr. heart rate/contractility
decr. blood pressure
decr. pupil size and increase outflow of aqueous humor from the eye
incr. salivation
incr. bronchial muscle tone
incr. intestinal muscle contraction
incr. bladder detrusor muscle contraction; incr. voiding


What mAChR, specifically, decreases heart rate?



What mAChR, specifically, cases vasodialtion?

m3 receptor on endothelial cells


Bethanechol: uses, MOA

prevent urinary retention; stimulate GI to treat postop abdominal distention
mAChR agonist


What are contraindications for drugs like bethanechol?

this is a mAChR agonist. so, contraindicated in pts w asthma, coronary insufficiency, peptic ulcers (incr. gland secretions in stomach? my personal speculation)


How do you counter toxicities from bethanechol?



Atropine: drug type

muscarinic receptor antagonist


What are the effects of atropine on the body?

decr. secretions and decr. GI motility
incr. HR and conduction: antidote for poisoning by AChE inhibitors
mydriasis (pupil dilation): eye exams. causes cyclolegia: no ability to focus on close objects; bad for glaucoma (incr. intraocular pressure
bronchial dilation
few CNS effects at normal doses; too high causes hallucinations


What type of drug is scopolamine? disadvantages? uses?

muscarinic receptor antagonist
used for motion sickness treatment
disadvantage: CNS side effects


What are the five main uses for acetylcholinesterase inhibitors?

1. treat myasthenia gravis
2. treat glaucoma
3. produce miosis (pupil contraction)
4. Alzheimer's disease
5. poisons


What are the 3 general classes of AChE inhibitors?

very short acting, reversible
short acting, reversible


What is edrophonium/tensilon?
type, duration of action, uses

AChE inhibitor
binds reversibly to AChE
short duration of action
diagnoses of myasthenia gravis


What is neostigmine? type, target, duration of action, uses

AChE inhibitor
covalently bound to AChE --> carbamylated enzyme that is slowly hydrolyzed to reactivate the enzyme (3-6 hr half life)
treatment of myasthenia gravis or glaucoma


How do sarin and other nerve gases/insecticides work?

AChE inhibitor
irreversible modification of the AChE enzyme: phosphrylation at the active site. (one irreversible class of molecule is nonetheless used to treat glaucoma)


What is pralidoxime (2-PAM)? How does it work?

regenerates unphosphorylated AChE from AChE that has been phosphorylated by exposure to nerve gas/insecticide. antidoe to AChE poisoning
must be used quickly- other wise the phosphylated enzyme ages and can't be modified with prlidoxime.


How do you treat AChE poisoning?

pralidoxime and atropine. FAST.


symptoms of AChE poisoning

too much ACh at receptors.
Early: restlessness, abdominal distress (intestinal spasms), involuntary defecation, frequent urination
then, incr. salivation, lacrimation, sweating
Then, bronchiolar constriction, convulsions, paralysis, body stops breathing.


What are newer uses for of mAChR antagonists?

urinary incontinence
Parkinson's disease
stomach ulcers


What is donepezil?

most widely used alzheimer's drug
reversible AChE inhibitor with high selectivity for AChE over butyrylcholinesterase. also good for parkinsonian dementia.