How Plaquenil May Work

I struggled for 36 years in Rheumatology to figure out how Plaquenil works in our diseases, and never did.  But I think I might understand, at least in part, how it’s working in its new role as our savior from Mr. coronavirus.

It’s just a matter of simple chemistry.  OHC (hydroxychloroquine: Plaquenil) accumulates in acidic intracellular organelles, including the Golgi where coronavirus replicate, and does its diprotic base thing to raise the ambient pH, thus dousing our unwelcome viral intruders with Drano.

from a 16 year old text:

HCQ and chloroquine are aromatic two-ringed 4-amino quinolone compounds; quinacrine has an additional aromatic ring with a methoxy group (Fig. 42.5 ). All three compounds are weak diprotic bases, a property that facilitates intracellular accumulation of the compounds in acidic organelles. At neutral pH of serum and interstitial fluids, antimalarials are uncharged and pass freely across cell membranes (295 ). Within the mildly acidic milieu of intracellular vesicles, the compounds become protonated and no longer freely diffuse across organelle membranes. The resulting partition gradient for uncharged drug may lead to over 100-fold excess concentration of drug within acidic vesicles (296 ). Increases in the pH of intracellular vesicles within malarial parasites resulting in impaired enzymatic breakdown of hemoglobin nutrients and impaired assembly and function of malarial proteins constitute proposed antiparasitic mechanisms of antimalarial efficacy.

From: Chatham WW.  Traditional Disease-Modifying Antirheumatic Drugs: Gold Compounds D-Penicillamine Sulfasalazine and Antimalarials, in Arthritis and Allied Conditions: A Textbook of Rheumatology, WJ Koopman and LW Moreland, Editors.  Fifteenth edition.  2004, Lippincott Williams & Wilkins: Baltimore.  pp 280-309

Published by rike52

I retired from the Rheumatology division of Michigan Medicine end of June '19 after 36 years there. Upon hitting Ann Arbor for the second time (I went to school here) it took me almost 8 months to meet Kathy, 17 months to buy her a house (on Harbal, where we still live), and 37 months to marry her. Kids never came, but we've been blessed with a crowd of colleagues, friends, neighbors and family that continues to grow. Lots of them are going to show up in this log eventually. Stay tuned.

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