Hydroxychloroquine is an antimalarial medication used to treat uncomplicated cases of malaria and for chemoprophylaxis in specific regions. Also a disease modifying anti-rheumatic drug (DMARD) indicated for treatment of rheumatoid arthritis and lupus erythematosus. Hydroxychloroquine is an aminoquinoline like chloroquine. Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported. Hydroxychloroquine is also used for the prophylaxis of malaria in regions where chloroquine resistance is unlikely. It was developed during World War II as a derivative of quinacrine with less severe side effects. The FDA emergency use authorization for hydroxychloroquine and chloroquine in the treatment of COVID-19 was revoked on 15 June 2020. The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite. Altering the pH of the lysozomes also reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements. It can also inhibit heme polymerase which causes an accumulation of toxic heme or ferriprotoporphyrin IX in the vacuole of the malaria cell. This leads to cell and parasite death.

Hydroxychloroquine Pathway References