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Treatment of extraintestinal amebiasis. Three week supply OR 2. As an alkaloid, it is accumulated in the food vacuoles of Plasmodium species, especially Plasmodium falciparum. It acts by inhibiting the hemozoin biocrystallization , thus facilitating an aggregation of cytotoxic heme.


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Quinine is less effective and more toxic as a blood schizonticidal agent than chloroquine ; however, it is still very effective and widely used in the treatment of acute cases of severe P. It is especially useful in areas where there is known to be a high level of resistance to chloroquine, mefloquine , and sulfa drug combinations with pyrimethamine.

Quinine is also used in post-exposure treatment of individuals returning from an area where malaria is endemic.

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The treatment regimen of quinine is complex and is determined largely by the parasite's level of resistance and the reason for drug therapy i. Doses can be given by oral, intravenous or intramuscular routes. The recommended method depends on the urgency of treatment and the available resources i. Use of quinine is characterised by a frequently experienced syndrome called cinchonism. Tinnitus a hearing impairment , rashes, vertigo , nausea, vomiting and abdominal pain are the most common symptoms. Neurological effects are experienced in some cases due to the drug's neurotoxic properties.

These actions are mediated through the interactions of quinine causing a decrease in the excitability of the motor neuron end plates. This often results in functional impairment of the eighth cranial nerve , resulting in confusion, delirium and coma. Quinine can cause hypoglycaemia through its action of stimulating insulin secretion; this occurs in therapeutic doses and therefore it is advised that glucose levels are monitored in all patients every 4—6 hours.

This effect can be exaggerated in pregnancy and therefore additional care in administering and monitoring the dosage is essential. Repeated or over-dosage can result in renal failure and death through depression of the respiratory system. Quinimax and quinidine are the two most commonly used alkaloids related to quinine in the treatment or prevention of malaria.

Quinimax is a combination of four alkaloids quinine, quinidine, cinchoine and cinchonidine. This combination has been shown in several studies to be more effective than quinine, supposedly due to a synergistic action between the four cinchona derivatives. Quinidine is a direct derivative of quinine. It is a distereoisomer , thus having similar anti-malarial properties to the parent compound. Quinidine is recommended only for the treatment of severe cases of malaria. Warburg's tincture was a febrifuge developed by Carl Warburg in , which included quinine as a key ingredient.

In the 19th-century it was a well-known anti-malarial drug. Although originally sold as a secret medicine, Warburg's tincture was highly regarded by many eminent medical professionals who considered it as being superior to quinine e. Surgeon-General W. Warburg's tincture appeared in Martindale: The complete drug reference from until about The formula was published in The Lancet Chloroquine was, until recently, the most widely used anti-malarial.

It was the original prototype from which most methods of treatment are derived. It is also the least expensive, best tested and safest of all available drugs. The emergence of drug-resistant parasitic strains is rapidly decreasing its effectiveness; however, it is still the first-line drug of choice in most sub-Saharan African countries. It is now suggested that it is used in combination with other antimalarial drugs to extend its effective usage. Chloroquine is a 4-aminoquinolone compound with a complicated and still unclear mechanism of action.

It is believed to reach high concentrations in the vacuoles of the parasite, which, due to its alkaline nature, raises the internal pH. It controls the conversion of toxic heme to hemozoin by inhibiting the biocrystallization of hemozoin , thus poisoning the parasite through excess levels of toxicity. Other potential mechanisms through which it may act include interfering with the biosynthesis of parasitic nucleic acids and the formation of a chloroquine-haem or chloroquine- DNA complex. The most significant level of activity found is against all forms of the schizonts with the obvious exception of chloroquine-resistant P.

Chloroquine also has a significant anti-pyretic and anti-inflammatory effect when used to treat P. According to a report on the Science and Development Network website's sub-Saharan Africa section, there is very little drug resistance among children infected with malaria on the island of Madagascar, but what drug resistance there is exists against chloroquinine. Chloroquine is only recommended as a prophylactic drug in regions only affected by P. Chloroquine has been used in the treatment of malaria for many years and no abortifacient or teratogenic effects have been reported during this time; therefore, it is considered very safe to use during pregnancy.

However, itching can occur at intolerable level and Chloroquinine can be a provocation factor of psoriasis. Amodiaquine is a 4-aminoquinolone anti-malarial drug similar in structure and mechanism of action to chloroquine. Amodiaquine has tended to be administered in areas of chloroquine resistance while some patients prefer its tendency to cause less itching than chloroquine. Amodiaquine is now available in a combined formulation with artesunate ASAQ and is among the artemisinin-combination therapies recommended by the World Health Organization.

Adverse reactions are generally similar in severity and type to that seen in chloroquine treatment. In addition, bradycardia , itching, nausea, vomiting and some abdominal pain have been recorded. Some blood and hepatic disorders have also been seen in a small number of patients.

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Pyrimethamine is used in the treatment of uncomplicated malaria. It is particularly useful in cases of chloroquine-resistant P. It acts by inhibiting dihydrofolate reductase in the parasite thus preventing the biosynthesis of purines and pyrimidines , thereby halting the processes of DNA replication , cell division and reproduction. It acts primarily on the schizonts during the erythrocytic phase, and nowadays is only used in concert with a sulfonamide.

Proguanil chloroguanide is a biguanide ; a synthetic derivative of pyrimidine. It was developed in by a British Antimalarial research group. It has many mechanisms of action but primarily is mediated through conversion to the active metabolite cycloguanil.

This inhibits the malarial dihydrofolate reductase enzyme. Its most prominent effect is on the primary tissue stages of P. It has no known effect against hypnozoites therefore is not used in the prevention of relapse.

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It has a weak blood schizonticidal activity and is not recommended for therapy of acute infection. However it is useful in prophylaxis when combined with atovaquone or chloroquine in areas where there is no chloroquine resistance. The pharmacokinetic profile of the drugs indicates that a half dose, twice daily maintains the plasma levels with a greater level of consistency, thus giving a greater level of protection.

The proguanil- chloroquine combination does not provide effective protection against resistant strains of P. There are very few side effects to proguanil, with slight hair loss and mouth ulcers being occasionally reported following prophylactic use. Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.

Sulfadoxine and sulfamethoxypyridazine are specific inhibitors of the enzyme dihydropteroate synthetase in the tetrahydrofolate synthesis pathway of malaria parasites. Sulfonamides act on the schizont stages of the erythrocytic asexual cycle. When administered alone sulfonamides are not efficacious in treating malaria but co-administration with the antifolate pyrimethamine , most commonly as fixed-dose sulfadoxine-pyrimethamine Fansidar , produces synergistic effects sufficient to cure sensitive strains of malaria. Sulfonamides are not recommended for chemoprophylaxis because of rare but severe skin reactions experienced.

However it is used frequently for clinical episodes of the disease.


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Mefloquine was developed during the Vietnam War and is chemically related to quinine. It was developed to protect American troops against multi-drug resistant P. It is a very potent blood schizonticide with a long half-life. It is thought to act by forming toxic heme complexes that damage parasitic food vacuoles. Mefloquine is effective in prophylaxis and for acute therapy. It is now used solely for the prevention of resistant strains of P. The major commercial manufacturer of mefloquine-based malaria treatment is Roche Pharmaceuticals, which markets the drug under the trade name " Lariam ".

The increased dosage is associated with a much greater level of intolerance, most noticeably in young children; with the drug inducing vomiting and esophagitis.