Arrgh. This post has brought me out of SD retirement. My second career, no, third career was in a clinical chemistry research lab, which started and spun off a commercial pharmacogenetic (AKA PGX in the biz) testing lab. CYP3A4 is an enzyme that metabolizes certain drugs, and several compounds in grapefruit juice attach themselves permanently to the enzyme, jamming it up. Enough jammed enzymes reduces metabolic capacity, and the active parent drug is not metabolized as quickly as it would be otherwise. So, someone can overdose on a normal dose of medication when eating or drinking grapefruit.
But that’s just half of the story. There are other drug metabolizing enzymes: CYP1A2, 2D6, 2C9, and 2C19. They can be interfered with by other drugs or compounds, creating other unwanted reactions and potential overdoses. Point mutations in the genes that code for the enzymes can also occur that reduce the speed at which an enzyme can metabolize a drug. Back in the day, we were all over creating a dosing algorithm for Warfarin based on these point mutations in CYP2D6 (I think) and VKORC1. Today, as I understand it, PGX testing is most effective for dosing psychiatric and some chemotherapeutic drugs.
I have a mutation in CYP2C19 that makes me a slower metabolizer of some drugs, like Prilosec. I used that to my advantage years ago when I had intractable heartburn from a hernia. I could take 1 OTC Prilosec every 36 hours instead of the usual 18-24 hours.
Going even further (indulge me here), some Asian populations have a slow ADH1 enzyme that is part of the alcohol metabolic process. They have a lower tolerance for alcohol and more adverse effects. Native North Americans descended from Asians with this slow ADH1 have long struggled with alcoholic products introduced by people with European ancestry who have a normally functioning ADH1 enzyme.