Which drug should be avoided in acute intermittent porphyria due to porphyrinogenic potential?

Which drug should be avoided in acute intermittent porphyria due to porphyrinogenic potential?

• A. Barbiturates
• B. Etomidate
• C. Ketamine
• D. Any drug that induces ALA synthase

Answer: (D)

In acute intermittent porphyria, the liver’s rate-limiting step for heme synthesis is ALA synthase. Drugs that induce ALA synthase push more precursor material (ALA and porphyrinogens) into the pathway. Because the downstream defect in AIP is at porphobilinogen deaminase, this extra flux leads to accumulation of toxic porphyrin precursors and triggers acute attacks with neurovisceral symptoms. Thus the best rule is to avoid any drug that induces ALA synthase, since it directly raises the production of porphyrin precursors. Some agents historically labeled porphyrinogenic are known to induce the enzyme, but the overarching concept is that induction of ALA synthase promotes attacks.

In acute intermittent porphyria, the liver’s rate-limiting step for heme synthesis is ALA synthase. Drugs that induce ALA synthase push more precursor material (ALA and porphyrinogens) into the pathway. Because the downstream defect in AIP is at porphobilinogen deaminase, this extra flux leads to accumulation of toxic porphyrin precursors and triggers acute attacks with neurovisceral symptoms. Thus the best rule is to avoid any drug that induces ALA synthase, since it directly raises the production of porphyrin precursors. Some agents historically labeled porphyrinogenic are known to induce the enzyme, but the overarching concept is that induction of ALA synthase promotes attacks.