Why does muscarinic overstimulation cause respiratory depression?

[Ruban]

So I was reading pharm yesterday on parathion, an organophosphate acetylcholinesterase inhibitor. One of the side effects is respiratory depression/bradycardia. Anyone know why this occurs? I understand the other side effects (lacrimation, salivation, diarrhea, etc, since they are just excess parasympathetic-type stimulation), but why does respiratory depression occur?

Thanks!

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[Idiopathic]

I think those effects are mediated by inability of the nicotinic muscle end-plate receptors to inactivate and repolarize, since toxicity results in accumulation of ACh everywhere, not just at the M receptors. Muscle weakness will be evident.

 

[Harps]

I think those effects are mediated by inability of the nicotinic muscle end-plate receptors to inactivate and repolarize, since toxicity results in accumulation of ACh everywhere, not just at the M receptors. Muscle weakness will be evident.

Exactly right! I believe fast twitch muscles are responsible for respiration. These muscles show an all-or-none action potential response. Thus, as Idio stated, the constant presence of ACh would cause long depolarization and prevent the muscles from repolarizing. You should verify this info.!

-Harps

 

[Hosehead]

yep, that logic makes sense. I was just studying this stuff for a pharm final on friday I think the bradycardia would also be caused by an increase in parasympathetic stimulation to the SA and AV node. Happy studying!

 

[nicholonious]

...with Harps. It is also important to note that Muscarinic receptors are principally found in blood vessels and heart tissue. By applying agonists to these receptors in their given locations, a marked decrease in heart rate (bradycardia) and hypotension occur. For respiratory depression, would this be due to vagal afferents ascending toward the medulla by means of baroreceptor reflex (decrease in blood pressure)?

Harps, raincheck on the borders/plutos get together, nah mean?

 

[daisygirl]

...with Harps. It is also important to note that Muscarinic receptors are principally found in blood vessels and heart tissue. By applying agonists to these receptors in their given locations, a marked decrease in heart rate (bradycardia) and hypotension occur. For respiratory depression, would this be due to vagal afferents ascending toward the medulla by means of baroreceptor reflex (decrease in blood pressure)?

Harps, raincheck on the borders/plutos get together, nah mean?

If I remember correctly from pharm, blood vessels are not innervated via the parasympathetic system (so there is no ps innervation via muscarinic receptors). The blood vessels only receive innervation via the sympathetic system's adrenergic receptors. Muscarinic receptors are primarily located in the heart, smooth muscle (think GI system) and glands.

I have a question now. I vaguely remember hearing that blood vessels do have receptors for ach- but they are kind of like receptors dangling in the wind since they are not connected to nerves. If I am remembering correctly, these 'dangling receptors' are remnant receptors (i.e. birds DO have muscarinic receptors...has something to do with flight). Although the receptors do exist; they don't do anything since ach is not floating around in the vasculature. I don't know if I'm making this up...but I do remember hearing something like this

 

[azzarah]

If I remember correctly from pharm, blood vessels are not innervated via the parasympathetic system (so there is no ps innervation via muscarinic receptors). The blood vessels only receive innervation via the sympathetic system's adrenergic receptors. Muscarinic receptors are primarily located in the heart, smooth muscle (think GI system) and glands.

I have a question now. I vaguely remember hearing that blood vessels do have receptors for ach- but they are kind of like receptors dangling in the wind since they are not connected to nerves. If I am remembering correctly, these 'dangling receptors' are remnant receptors (i.e. birds DO have muscarinic receptors...has something to do with flight). Although the receptors do exist; they don't do anything since ach is not floating around in the vasculature. I don't know if I'm making this up...but I do remember hearing something like this

I remember that if the vessel endothelium is damaged, Ach will cause vascular smooth muscle contraction. In normal vessels, Ach doesn't do anything I don't think.

 

[Ruban]

Thanks for all the replies folks.
So to confirm, the effects are mediated by effects on the nerves that depolarize the diaphragm and accessory breathing muscles, rather than a CNS effect that acts on the respiratory center?

 

[Harps]

...with Harps. It is also important to note that Muscarinic receptors are principally found in blood vessels and heart tissue. By applying agonists to these receptors in their given locations, a marked decrease in heart rate (bradycardia) and hypotension occur. For respiratory depression, would this be due to vagal afferents ascending toward the medulla by means of baroreceptor reflex (decrease in blood pressure)?

Harps, raincheck on the borders/plutos get together, nah mean?

I guess NPB does come in handy...once in a while. Yeah, no worries. We'll meet up soon

-Harps

 

[The Gun]

Vascular endothelium has non-innervated muscarinic receptors. A low dose of ACh will cause vasodilation mediated at these receptors. If the dose is increased, you have to account for reflex response. Pre-treatment with Atropine, obviously, antagonizes this effect. Classic experiment.

 

[Samoa]

Nerds, all of you!