LARIDOX AQ DT

Indications

• Malaria caused by Plasmodium falciparum
• Rheumatoid arthritis
• Lupus erythematosus

Mechanism of action

The exact mechanism of action of amodiaquine is not completely understood. It is believed to inhibit heme polymerase activity, leading to an accumulation of free heme, which is toxic to malarial parasites. Amodiaquine binds to free heme, preventing its conversion to a less toxic form, and this drug-heme complex disrupts membrane function within the parasite. Additionally, it may interfere with protein synthesis by binding to nucleoproteins and intercalating into double-stranded DNA, inhibiting DNA and RNA polymerase. Furthermore, it is known to concentrate in the digestive vacuoles of the parasites, increasing vacuolar pH and impairing the parasite's ability to metabolize hemoglobin.

Pharmacodynamics

Amodiaquine is effective against malaria and exhibits anti-inflammatory properties. It can depress cardiac muscle function, impair conduction, and produce vasodilation, which may lead to hypotension. Other side effects include respiratory depression, diplopia, dizziness, and nausea. While its effectiveness is comparable to that of chloroquine, the development of resistance to amodiaquine has been documented. The drug's adverse effects and potential for toxicity necessitate monitoring during treatment.

Pharmacokinetics

Amodiaquine is well absorbed after oral administration. It undergoes hepatic metabolism, with its active metabolite contributing to its antimalarial effects. The pharmacokinetics can be influenced by factors such as hepatic function and concurrent medications. The elimination half-life of amodiaquine may vary, and it is important to consider individual patient factors when determining dosing regimens.

Contra-indications

• Hypersensitivity to amodiaquine or any of its components
• Severe liver impairment
• History of retinopathy related to 4-aminoquinoline derivatives
• Severe hematological disorders, including agranulocytosis and aplastic anemia

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Diplopia
• Hypotension
• Cardiac arrhythmias
• Hepatotoxicity
• Skin rashes
• Agranulocytosis

Interactions

• May enhance effects of anticoagulants
• Concomitant use with other antimalarials may increase risk of toxicity
• Caution with drugs that can cause hepatotoxicity
• May affect the metabolism of drugs that are substrates for CYP450 enzymes

Precautions

• Monitor liver function during treatment
• Use with caution in patients with a history of cardiovascular disease
• Assess for signs of hematological disorders
• Consider potential for cross-resistance with other 4-aminoquinoline derivatives

Pregnancy

Amodiaquine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. It is advised to refer to local guidelines.

Breast-feeding

Amodiaquine is excreted in breast milk. Caution is advised when administering to breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Mechanism of action

The mechanism of plasmodicidal action of amodiaquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. The drug binds the free heme preventing the parasite from converting it to a form less toxic. This drug-heme complex is toxic and disrupts membrane function. Amodiaquine is a Mannich base 4-aminoquinoline with a mode of action similar to that of chloroquine. It is effective against some chloroquine-resistant strains of P. falciparum, although there is cross-resistance. The 4-aminoquinoline derivatives appear to bind to nucleoproteins and interfere with protein synthesis in susceptible organisms; the drugs intercalate readily into double-stranded DNA and inhibit both DNA and RNA polymerase. In addition, the drugs apparently concentrate in parasite digestive vacuoles, increase the pH of the vacuoles, and interfere with the parasite's ability to metabolize and utilize erythrocyte hemoglobin. Plasmodial forms that do not have digestive vacuoles and do not utilize hemoglobin, such as exoerythrocytic forms, are not affected by /these medications/. The 4-aminoquinoline derivatives ... have anti-inflammatory activity; however, the mechanism(s) of action of the drugs in the treatment of rheumatoid arthritis and lupus erythematosus has not been determined. /4-aminoquinoline derivatives/ reportedly antagonizes histamine in vitro, has antiserotonin effects, and inhibits prostaglandin effects in mammalian cells presumably by inhibiting conversion of arachidonic acid to prostaglandin F2. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension; they depress respiration and cause diplopia, dizziness and nausea.

Pharmacodynamics

Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 40 years. Amodiaquine is at least as effective as chloroquine, and is effective against some chloroquine-resistant strains, although resistance to amodiaquine has been reported. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension. They depress respiration and cause diplopia, dizziness and nausea.