Qbook: Pharm test 1, question 8 Please help

[Plinko]

I came across a question in the Qbook that I can't make sense of.

My friend and I have been going over it and keep running into road blocks. If one were given Norepi, wouldn't the B1 activity cause an increased heart rate, not decreased as the correct answer says. I know there would be eventual refelx bradycardia with Norepi, but the graph has the MAP going up simultaneously with the HR going down. I can't see how this could happen. Additionally, I don't see how hexamthonium has such a specific effect as they indicate it has. As it is a gangloin blocker, I don't see how it decreases MAP, but increases HR. Maybe my reading comprehension skills aren't so good these days, and the explanation for the answer is sufficient. Can anyone explain this in another way to help me and my classmate out?

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[moo]

I came across a question in the Qbook that I can't make sense of.

My friend and I have been going over it and keep running into road blocks. If one were given Norepi, wouldn't the B1 activity cause an increased heart rate, not decreased as the correct answer says. I know there would be eventual refelx bradycardia with Norepi, but the graph has the MAP going up simultaneously with the HR going down. I can't see how this could happen. Additionally, I don't see how hexamthonium has such a specific effect as they indicate it has. As it is a gangloin blocker, I don't see how it decreases MAP, but increases HR. Maybe my reading comprehension skills aren't so good these days, and the explanation for the answer is sufficient. Can anyone explain this in another way to help me and classmate out?

You always deal with the effect of NE on the vasculature first. NE vasoconstricts so the bradycardia is in fact due to a reflex. Gangionic blockers block whatever effects that predominate. In this case, it decreases MAP because the cholinergic nicotinic receptor is blocked, decreasing noradrenergic outflow. The increased HR is due to a reflex once again.

 

[Plinko]

Thanks moo. I didn't add this in the original post. The third phase is an increase in MAP and HR subsequent to readministration of Norepi. Why are the effects of Norepi different this time around? That is, why wouldn't you have reflex bradycardia once again despite prior adminstration of hexamethonium?

 

[BrooklynDO]

Thanks moo. I didn't add this in the original post. The third phase is an increase in MAP and HR subsequent to readministration of Norepi. Why are the effects of Norepi different this time around? That is, why wouldn't you have reflex bradycardia once again despite prior adminstration of hexamethonium?

I remember reading somewhere that hexamethonium blocks reflex bradicardia... i THINK it was FA im not sure
as to why you dont get the brady, i think its because since the hexameth is still there...still blocking the reflex

 

[nuclearrabbit77]

I came across a question in the Qbook that I can't make sense of.

My friend and I have been going over it and keep running into road blocks. If one were given Norepi, wouldn't the B1 activity cause an increased heart rate, not decreased as the correct answer says. I know there would be eventual refelx bradycardia with Norepi, but the graph has the MAP going up simultaneously with the HR going down. I can't see how this could happen. Additionally, I don't see how hexamthonium has such a specific effect as they indicate it has. As it is a gangloin blocker, I don't see how it decreases MAP, but increases HR. Maybe my reading comprehension skills aren't so good these days, and the explanation for the answer is sufficient. Can anyone explain this in another way to help me and my classmate out?

in regards to hexamethonium, it is a ganglionic blocker which can affect parasympathetic and also sympathetics. the way to understand how the body will respond is to know what the predominate "tone" controls which body system. for example, the GI system is predominately under parasympathetic tone, while the peripheral vasculature is under sympathetic tone. key: the heart is mainly under parasympathetic control. hexamethonium will decrease the predominate tone--so with the systems mentioned you'd get loss of parasympathetic GI and loss of sympathetic peripheral vasculature tone, giving constipation, decrease in GI motility,etc, and also, a decrease in MAP.


Giving norepinephrine can directly stimulate end-organ targets, due to circulation in the blood and isn't dependent on the normal pathway of using the presynaptic ganglion,etc. in this case it, causing an increased MAP and Heart rate at the alpha 1 and beta 1 receptors. The body can not respond in a homeostatic fashion because homeostatic mechanism are dependent on the presynaptic ganglion/pathways and is blocked by hexamethonium.


to make a long story short, hexamethonium is blocking the conduit for homeostatic mechanisms, and initself hexamethonium will release organ systems from their predominant parasympathetic/sympathetic tone.

 

[annushka]

A good method that I adapted was to always ask myself where the receptor is, and which receptors predominate where. Because if you have 1000 muscarinic receptors and 10 adrenergic receptors on a particular organ, it's obvious to see that the muscarinic effect will win out. It's also obvious that this will be the main effect blocked as you use a ganglionic blocker.

So...
adrenergic receptors predominate in vasculature and ? (there was a second one but i totally forgot it)

cholinergic (muscarinic) receptors predominate almost everywhere but the vasculature. most notably, the heart has a predominance of muscarinic receptors (and not adrenergic).

remember the main nerve innervating the heart is vagus which keeps it under tight parasympathetic control, especially when the blood pressure rises you will get bradycardia. norepi acts on apha more than on beta, so it will mainly give you vasoconstriction, thus increasing the pressure and (reflexively) this will increase firing of PS neurons in vagus, giving you bradycardia.
then, you give hexamethonium, which blocks the PS response. so you have no PS at all, the heart rate rises a little.
then you hit again with norepi, and this time it's beta effect is more pronounced, giving you tachycardia (since it's not opposed by alpha)

with epi--you have stimulation of b2 as well as alphas, so you will get both vasocontstriction (raised systolic) and vasodilation (raised diastolic)--this cancels out and your MAP will not change much. it might even decrease, and the reflex would then be to shut off PS control of the heart and give you tachycardia.

sorry for the long explanation, but when i write things out like this it keeps me less confused

 

[BrooklynDO]

anna i think your epi explanation is a bit off.... epi depends on dose...high dose is mostly alpha, so increases systolic w/o much diastolic change...low dose is mostly beta, so it drops the diastolic (dec pvr) but mean may or may not change. as for norepi, without the block the vagus is able to overide the B1 of effect in response to the a1 effect. with the block , the reflex is gone and Nore now directly acticivates the B1 receptors, increasing hr.

 

[annushka]

i know about the effects of epi dose, but sometimes the question doesn't give you the dose...so i just assume it's a "medium dose" where both of these effects are present and they counteract each other (no change in map). it might be a silly way to remember it, but oh well i am silly.

 

[BrooklynDO]

i know about the effects of epi dose, but sometimes the question doesn't give you the dose...so i just assume it's a "medium dose" where both of these effects are present and they counteract each other (no change in map). it might be a silly way to remember it, but oh well i am silly.

and thats why i love sitting next to you in class for two years..when i was in class...

 

[Plinko]

Thanks guys. I get it now. You all should be writing the explanations for Kaplan.

 

[nuclearrabbit77]

could someone explain the mechanism of coronary and cerebral vasodilation from adenosine?

adenosine causes a decrease in cAMP, which should have a vasoconstrictive effect in smooth muscle. one of the side effects of adenosine is bronchoconstriction, which is consistent with a decrease in cAMP. (and this is where theophylline works, in an antagonistic fashion) but how does adenosine cause coronary vasodilation?

thanks

 

[BrooklynDO]

could someone explain the mechanism of coronary and cerebral vasodilation from adenosine?

adenosine causes a decrease in cAMP, which should have a vasoconstrictive effect in smooth muscle. one of the side effects of adenosine is bronchoconstriction, which is consistent with a decrease in cAMP. (and this is where theophylline works, in an antagonistic fashion) but how does adenosine cause coronary vasodilation?

thanks

from what i know it increases K current, hyperpolarizing the smooth muscle tissue.... at least thats what Mr Katzung told me