Phenobarbitone can precipitate acute intermittent porphyria (AIP)
Phenobarbital acts as a potent inducer of hepatic cytochrome P450 enzymes, which in turn can increase the activity of ALA synthase, leading to overproduction of porphyrins.
by inducing cytochrome P450 enzymes it increasing heme synthesis, and accumulating toxic precursors (ALA and PBG).
This triggers acute attacks with severe abdominal pain, neuropsychiatric symptoms, autonomic dysfunction, and muscle weakness.
Safe alternatives include benzodiazepines (lorazepam, diazepam) for seizures and gabapentin for neuropathic pain.