Step I Barbiturates poryphrias

[Transformers]

Could someone explain what barbiturates do in causing acute intermittent porhypria...like do the drugs inhibit Prophobilinoen deaminase?

 

[Jamiu22]

Could someone explain what barbiturates do in causing acute intermittent porhypria...like do the drugs inhibit Prophobilinoen deaminase?

Many commonly used drugs trigger porphyric crisis by decreasing heme. (2) Barbiturates induce the cytochrome P450 system; this incorporates more heme into the new cytochromes, thereby decreasing heme levels. Oral contraceptives cause destruction of the heme group in cytochromes, requiring new heme for incorporation into cytochromes. Griseofulvin converts heme into N-methylated derivatives, which further inhibit heme synthesis.

http://anesthesiologyboards.com/pdfs/porphyria.pdf

 

[CaptainSSO]

My understanding is that they activate delta-aminolevulinic acid synthase.

 

[Transformers]

got it i think the idea is the liver p450 system (which uses heme)...it doesnt cause porphyria but rather PRECIPITATES it by diminishing heme in the p450 system causing u to rev up ALAS

 

[Henal Patel]

from my understanding ... Barbiturates are p450 inducers which will induce Heme Synthesis (heme-iron center in P450 enzymes). The pathogenesis of Acute Intermittent Porphyria is that heme synthesis is interrupted by enzyme deficiency (porphobilinogen deaminase) which results in a buildup of porphobilinogen. Inducing heme synthesis will only further increase this buildup and symptoms will precipitate.

 

[ulikedaggers]

from my understanding ... Barbiturates are p450 inducers which will induce Heme Synthesis (heme-iron center in P450 enzymes). The pathogenesis of Acute Intermittent Porphyria is that heme synthesis is interrupted by enzyme deficiency (porphobilinogen deaminase) which results in a buildup of porphobilinogen. Inducing heme synthesis will only further increase this buildup and symptoms will precipitate.

This. There's also a buildup of ALA in AIP. It may also be worth noting that hepatic porphyrias (like AIP) may be asymptomatic unless ALA synthase is induced by things like steroids, barbs, and periods of fasting.