SEPTEMBER 12, 2022
Written by Daniel Laub, M.D.
Colchicine
Colchicine is one of the oldest and potent-est anti-inflammatories we have -dating to the 6th century. It is effective in treating gout, pericarditis, and even the rare Familial Mediterranean Fever – think body attacking itself – vv painful. Colchicine works by blocking microtubule (MT) growth. Remember that MTs are structural proteins, with roles in axonal-transport channels, cilia/flagella engines, walkways (mitotic spindles) along which chromosomes split during M phase. MTs are constantly growing and shrinking via a process called treadmilling – alpha subunits are added to the head to extend, and then beta subunits are removed from the tail to shorten. They be important, and you’re dead without them. Mechanistically, colchicine works like vinca alkaloids and podophyllotoxin: it binds MTs at the alpha-beta interface and prevents polymerization, sort of like the OG HIV drug AZT or the herpes drug acyclovir, except those prevent DNA polymerization. Colchicine is great at blunting the inflammatory response via action on neutrophils. However, it acts on ALL cells, and the therapeutic window is very narrow, making it a dirty, nasty drug on which to OD. First thing to expect is GI symptoms (GI tract always be replicating), think n/v/d, and possibly hemorrhagic enteritis. This can lead to volume depletion. Following that comes the pancytopenia (with profound leukopenia, like WBC <1k), and then can come arrhythmias. Badness on badness on badness on a bagel. Additionally, there’s no available antidote, and dialysis doesn’t work. Treatment: supportive care – think fluid resus, ECMO, and hope. One last thing to brighten your day – drugs like statins and PPIs inhibit p-GP, the pump that removes this poison from cells and the brain. So, those drugs can lead to an increase in [colchicine]. Let’s hope we never have to deal with a patient experiencing colchicine toxicity, because there’s not much we can do, and the outcome is often grim. Have a lovely day.
