Clozaril and Aagranulocytosis

[7175pank]

Hey guys,

This is just a general question that I've had but haven't had much luck finding an answer so I'm hoping maybe you guys can point me in the right direction.

As you probably guessed from the title it has to do with clozaril and agranulocytosis. I know about the risk of agranulocytosis but I can't find any information regarding why there is a risk in the first place. Can anyone explain why clozaril causes agranulocytosis or point me in the right direction? Or is this something that still hasn't been resolved?

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[shan564]

I'm pretty sure it's just a random idiosyncrasy, just like the other drugs that cause agranulocytosis (methimazole, etc.).

 

[7175pank]

I'm pretty sure it's just a random idiosyncrasy, just like the other drugs that cause agranulocytosis (methimazole, etc.).

Any idea as to why that is though?

 

[shan564]

From a quick google search, it seems that several journal articles say the exact mechanism is unclear, but several theories have been proposed.

Here's one good review article: http://pmj.bmj.com/content/81/959/545.full

And a quote from that article: "The exact mechanism of clozapine induced agranulocytosis is unclear. It has been postulated that clozapine is metabolised to a nitrenium ion.8 The binding of this ion to neutrophils may result in agranulocytosis. Antineutrophil antibodies may be involved in mediating agranulocytosis.9 Some human leucocyte antigen (HLA) alleles, for example the HLA B38 phenotype in Ashkenazi Jews,10 have been shown to be associated with clozapine induced agranulocytosis."

 

[7175pank]

From a quick google search, it seems that several journal articles say the exact mechanism is unclear, but several theories have been proposed.

Here's one good review article: http://pmj.bmj.com/content/81/959/545.full

And a quote from that article: "The exact mechanism of clozapine induced agranulocytosis is unclear. It has been postulated that clozapine is metabolised to a nitrenium ion.8 The binding of this ion to neutrophils may result in agranulocytosis. Antineutrophil antibodies may be involved in mediating agranulocytosis.9 Some human leucocyte antigen (HLA) alleles, for example the HLA B38 phenotype in Ashkenazi Jews,10 have been shown to be associated with clozapine induced agranulocytosis."

Thanks