Chloroquine drug interactions

Melanin has been shown to form adducts with chloroquine, paraquat, and clindamycin. The significance of drug interaction with melanin has been discussed. 

Chloroquine is contraindicated in patients with known hypersensitivity. Precautions and interactions for chloroquine are provided in the discussion of the drug in the Antimalatial Dragp section. 

El-Ashry et al. [36] studied the complex formation between the bromophenol blue, primaquine, and other important aminoquinoline antimalarials. The colorimetric method used was described as simple and rapid and is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex show maxima at 415 420 nm with high apparent molar absorptivities. Beer s law was obeyed in the concentration range 1-8,2-10, and 2-12 pg/mL for amodiaquine hydrochloride, primaquine phosphate, and chloroquine phosphate, respectively. The method was applied to the determination of these drugs in certain formulations and the results were favorably comparable to the official methods. 

Quinine is the principal alkaloid derived from the bark of the cinchona tree. It has been used for malaria suppression for over 300 years. By 1959 it was superseded by other drugs, especially chloroquine. After widespread resistance to chloroquine became manifest quinine again became an important antimalarial. Its main uses are for the oral treatment of chloroquine-resistant falciparum malaria and for parenteral treatment of severe attacks of falciparum malaria. Quinine is a blood schizonticide with some gametocytocidal activity. It has no exoerythrocytic activity. Its mechanism of action is not well understood. It can interact with DNA, inhibiting strand separation and ultimately protein synthesis. Resistance of quinine has been increasing in South-East Asia. 

Chloroquine (Aralen) is one of several 4-aminoquino-line derivatives that display antimalarial activity. Chloroquine is particularly effective against intraerythrocytic forms because it is concentrated within the parasitized erythrocyte. This preferential drug accumulation appears to occur as a result of specific uptake mechanisms in the parasite. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++-calmodulin-mediated mechanisms. It also accumulates in the parasite s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. 

For over 300 years, the quinoline family of drugs, and chloroquine in particular, has been used as the primary treatment for malaria. Recent studies have demonstrated that this drug inhibits the aggregation of free heme into hemozoin, allowing levels of monomeric heme to rise until cell lysis occurs. Although the determined structure of hemozoin makes the polymer termination scheme proposed by Sullivan et al. unlikely, hemozoin drug heme interactions appear critical in the inhibition mechanism. Thus, researchers have identified the characteristics of... 

Praziquantel Interactions of this drug are reported with carbamazepine, phenytoin, dexamethasone, and chloroquine.182... 

The mechanism by which PfCRT confers resistance to chloroquine is still under discussion [75], The first aspect concerns the nature of the protein whether PfCRT, postulated to possess ten transmembrane helices, is considered as a member of the drug-metabolite transporter family of proteins [55, 76-78], Some authors discuss about the channel nature of the protein [79, 80], It has been suggested that the change of the charged lysine to uncharged threonine affects the electrostatic interaction with the diprotonated CQ [81]. In the mutated forms, the absence of electrostatic interactions allows the drug to cross the channel (Fig. 6). This results in the efflux of the drug out of the DV [81]. Note here that the reduced accumulation can be partially reversed by verapamil, a lipophilic compound (Fig. 5). 

Chloroquine can cause seizures in patients with epilepsy. The mechanism is uncertain, but it may include reductions in inhibitory neurotransmitters and pharmacokinetic interactions that alter anticonvulsant concentrations. Tonic-clonic convulsions were reported in four patients in whom chloroquine was part of a prophylactic regimen. Antiepileptic treatment was required to control the seizures. None had further seizures after withdrawal of the antimalarial drugs (9). 

Menting, J.G., Tilley, L., Deady, L.W., et al. (1997) The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from Plasmodium falciparum. Mol. Biochem. Parasitol. 88, 215-224. 

It is found that by limiting consideration to molecules with only one chiral center and therefore only one pair of enantiomers the usual physical and chemical properties are identical in a symmetrical environment. However, rates of reactions, even reactivity (e.g., metabolism reactions) and binding propensities may differ significantly in an asymmetric bioenvironment. There are cases where no differences are demonstrable. Both + and -cocaine are equipotent local anesthetics. Similarly, both enantiomers of chloroquine are equally effective antimalarial compounds. It is possible that in these instances the centers of asymmetry do not participate in drug-receptor interactions, or, more likely, that the interaction may involve only one or two points of contact. 

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