Pharmacokinetics<unk>  has similar pharmacokinetics to chloroquine, with rapid gastrointestinal absorption, large distribution volume, and elimination by the kidneys. Cytochrome P450 enzymes (CYP2D6, 2C8, 3A4 and 3A5) metabolize<unk>  to N-desethylhydroxychloroquine. Both agents also inhibit CYP2D6 activity and may interact with other medications that depend on this enzyme. Pharmacodynamics Antimalarials are lipophilic weak bases and easily pass plasma membranes. The free base form accumulates in lysosomes (acidic cytoplasmic vesicles) and is then protonated, resulting in concentrations within lysosomes up to 1000 times higher than in culture media. This increases the pH of the lysosome from four to six. Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect. Higher pH within lysosomes causes decreased intracellular processing, glycosylation and secretion of proteins with many immunologic and nonimmunologic consequences. These effects are believed to be the cause of a decreased immune cell functioning such as chemotaxis, phagocytosis and superoxide production by neutrophils.<unk>  is a weak diprotic base that can pass through the lipid cell membrane and preferentially concentrate in acidic cytoplasmic vesicles. The higher pH of these vesicles in macrophages or other antigen-presenting cells limits the association of autoantigenic (any) peptides with class II MHC molecules in the compartment for peptide loading and/or the subsequent processing and transport of the peptide-MHC complex to the cell membrane. Mechanism of action<unk>  increases lysosomal pH in antigen-presenting cells by two mechanisms: As a weak base, it is a proton acceptor and via this chemical interaction, its accumulation in lysozymes raises the intralysosomal pH, but this mechanism does not fully account for the effect of<unk>  on pH. Additionally, in parasites that are susceptible to<unk> , it interferes with the endocytosis and proteolysis of hemoglobin and inhibits the activity of lysosomal enzymes, thereby raising the lysosomal pH by more than 2 orders of magnitude over the weak base effect alone. In 2003, a novel mechanism was described wherein<unk>  inhibits stimulation of the toll-like receptor (TLR) 9 family receptors. TLRs are cellular receptors for microbial products that induce inflammatory responses through activation of the innate immune system. As with other quinoline antimalarial drugs, the antimalarial mechanism of action of quinine has not been fully resolved. The most accepted model is based on hydrochloroquinine and involves the inhibition of hemozoin biocrystallization, which facilitates the aggregation of cytotoxic heme. Free cytotoxic heme accumulates in the parasites, causing death.<unk>  increases the risk of low blood sugar through several mechanisms. These include decreased clearance of the hormone insulin from the blood, increased insulin sensitivity, and increased release of insulin from the pancreas.
Hydroxychloroquine
Azathioprine
Teriflunomide
Leflunomide
Tofacitinib
Etanercept
Cyclizine
Prednisolone