Ergotamine, Peripheral Ischemia, and CYP3A4

[Jamshyd]

I just got my hands on some OTC cafergot (ergotamine + Caffeine). I would like to take some just for the heck of it. But reading monograph on RXList, I see a warning about Peripheral Ischemia when taking ergotamine with CYP3A4 inhibitors.

The explanation for such a phenomenon, I found, was very weird. Apparently, CYP3A4 inhibition reverses ergotamine's uptake into the brain, resulting in high blood concentration.

My question is, WTF?

 

[fastandbulbous]

By peripheral ischaemia, I assume you're referring to the severe vasoconstriction that eventually leads to ergotism with all it's lovely symptoms like appendages/limbs falling off.

Best to only take ergotamine if you suffer from something like migraine. If you do decide to, make bloody sure you don't have undiagnosed Ranauds disease as then even a theraputic dose can have fingers & toes dropping of faster than a leper strumming a guitar...

 

[Limpet_Chicken]

Delightful analogy Fast, I'l haveto remember that one.

What country is ergotamine OTC in exactly? that country must be swarming with tripheads

 

[Jamshyd]

^ Thailand, and sadly, it is only swarming with clueless dirty drunks... (everything is OTC here, if one knows where to look... but things aren't always great, they gave me prozac when I asked for something for sleep ).

But anyways.. indeed, wonderful analogy

The question still remains though, how does CYP3A4 inhibition result in reversed uptake?

 

[kaskelot]

I have no formal education in these matters. My guess would be along the lines of this, by CYP3A4-inhibition ergotamine isn't metabolised and thus does not pass BBB in any form, instead it binds to peripheral 5-HT- or DA-receptors causing peripheral vasoconstriction and all sorts of horrid stuff follows. How else would the CYP3A4 make the ergotamine pass into the brain, if not through metabolising it?

But, I've got no edumacationary degrades, and really has no idea of how the relevant enzyme does its job. I'm not really sure what you mean by "reverse uptake" either.

Edit: Typo, 'enzymes' --> 'enzyme'.

 

[Ham-milton]

ergotamine certainly gets through the BBB. It wouldn't be very effective at constricting vessels in the brain otherwise, would it.

 

[hugo24]

I use Cafergot occasionally for Migraine like Headaches since the old Tonopan is no more available (contained Dihydroergotamine,Caffeine and Propyphenazone sp ).But I take only a half dose,the full dose leaves my chest a bit too constricted which was somewhat frightening at the first time.And the 100mg Caffeine is a little much as well,part. in the evening.

Shame on the assholes who wiped off the old great Tonopan from the market