Niacin flush and anti-histamines

[1dayatatime]

So FA says the flush is due to excess PG not histamine, but I remember reading and see all over the internet that the flush can be lessened by anti-h's...whaaaaaaaaa?

Also, does anyone know what Spironolactone actually does to Digoxin? Rx says it decreases digoxin's effect and DECREASES toxicity. Nature (*the* publication) says yes it does decrease digoxin's effect and decreases dig's renal CL but doesn't say anything directly about its toxicity. WebMD and some other sites says that Digoxin toxicity will INCREASE with Spiro and other K sparing diuretics. I never know what to do in these situations. I guess I dont really trust anything, esp Rx.

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[acciddropping]

Niacin's flush is due to PG and that's the reason why taking Asprin 30 mins before Niacin helps.
For Dixogxin, I am not sure but.... Digoxin blocks Na/K exchange pump, so you will have more K outside and more Na+ so consequently more Ca+ inside the cells ==> hence increased contractility and hyperklemia. So, would giving Spironolactone (which will also cause hyperkalemia) be dangerous then?

 

[periaqueductal]

So FA says the flush is due to excess PG not histamine, but I remember reading and see all over the internet that the flush can be lessened by anti-h's...whaaaaaaaaa?

Also, does anyone know what Spironolactone actually does to Digoxin? Rx says it decreases digoxin's effect and DECREASES toxicity. Nature (*the* publication) says yes it does decrease digoxin's effect and decreases dig's renal CL but doesn't say anything directly about its toxicity. WebMD and some other sites says that Digoxin toxicity will INCREASE with Spiro and other K sparing diuretics. I never know what to do in these situations. I guess I dont really trust anything, esp Rx.

PGs are definitely the mechanism of flush, our pharm lecturers were very adamant about this fact. Give COX inhibitors.
Digoxin competes with extracellular K+ for the Na/K ATPase pump, so increased extracellular K+ (as is caused by spironolactone) will cause less digoxin binding and efficacy. As far as understand, this will also cause less toxicity because digoxin isn't able to produce it's effects.

 

[Oblique]

Niacin's flush is due to PG and that's the reason why taking Asprin 30 mins before Niacin helps.
For Dixogxin, I am not sure but.... Digoxin blocks Na/K exchange pump, so you will have more K outside and more Na+ so consequently more Ca+ inside the cells ==> hence increased contractility and hyperklemia. So, would giving Spironolactone (which will also cause hyperkalemia) be dangerous then?

Does anyone know the mechanism behind this? What is the relationship between Niacin & PG?
Thanks

 

[surgok]

I guess it depends on what kind of toxicity you are talking about. Digoxin effect decreases with hyperkalemia so it's overall toxicity will decrease. Whereas if you are only looking at hyperkalemia as a side effect, you will see increased level of toxicity due to combined effect of spironolactone and digoxin.

 

[NeuroLAX]

Does anyone know the mechanism behind this? What is the relationship between Niacin & PG?
Thanks

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779993/pdf/ijcp0063-1369.pdf

"A significant portion of the effects of niacin on flushing results from activation of the niacin receptor G protein-coupled receptor 109A (GPR109A) in dermal Langerhans cells (12,13), leading to the production of prostaglandins, including prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2), which act on receptors in the capillaries."

"In Langerhans cells, niacin can activate GPR109A to increase intracellular Ca2+ (13). This Ca2+ increase triggers phospholipases, predominantly Phospholipase A2 (PLA2), to release arachidonic acid from cellular lipid stores (30)."

 

[CherryRedDracul]

I guess it depends on what kind of toxicity you are talking about. Digoxin effect decreases with hyperkalemia so it's overall toxicity will decrease. Whereas if you are only looking at hyperkalemia as a side effect, you will see increased level of toxicity due to combined effect of spironolactone and digoxin.

Since digoxin competes with K+ for its spot on the Na+/K+ pump, it is true that as serum potassium rises, digoxin toxicity theoretically decreases. But it's hyperkalemia that ironically reduces acute digoxin toxicity which is *ahem* hyperkalemia. By how much? No clue.

So, overall, my guess would be that hyperkalemia is the real thing you're worrying about. Beyond that, I wouldn't rack my brain over it too much for Step 1.

 

[1dayatatime]

thanks everyone! so it seems like it's def. done by PG's yet why does the internet say anti-h's work too? did your teachers say anti-h's work too?

 

[Oblique]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779993/pdf/ijcp0063-1369.pdf

"A significant portion of the effects of niacin on flushing results from activation of the niacin receptor G protein-coupled receptor 109A (GPR109A) in dermal Langerhans cells (12,13), leading to the production of prostaglandins, including prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2), which act on receptors in the capillaries."

"In Langerhans cells, niacin can activate GPR109A to increase intracellular Ca2+ (13). This Ca2+ increase triggers phospholipases, predominantly Phospholipase A2 (PLA2), to release arachidonic acid from cellular lipid stores (30)."

Thank you for looking this up. Very helpful!