java barcode generator library Protozoal & Helminthic Infections in Objective-C

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limited inadvertent use in pregnancy has apparently not led to fetal problems 8 Atovaquone plus proguanil (Malarone) Atovaquone, a hydroxynaphthoquinone, is not an effective antimalarial when used alone, due to rapid development of drug resistance However, Malarone, a fixed combination of atovaquone (250 mg) and proguanil (100 mg), has been shown to be highly effective for both the treatment and chemoprophylaxis of falciparum malaria, and it is now approved for both indications in the United States It also appears to be active against other species of malaria parasites Atovaquone is heavily protein-bound and has a half-life of 2 3 days It appears to act by disrupting mitochondrial electron transport Proguanil is an inhibitor of DHFR, as described above Unlike most other antimalarials, Malarone provides activity against both erythrocytic and hepatic stage parasites For treatment, Malarone is given at an adult dose of four tablets for 3 days For chemoprophylaxis, Malarone must be taken daily It has an advantage over mefloquine and doxycycline in requiring shorter periods of treatment before and after the period at risk for malaria transmission, due to activity against liver-stage parasites, but it is more expensive than the other agents It should be taken with food Malarone is generally well tolerated Adverse effects include abdominal pain, nausea, vomiting, diarrhea, headache, and rash, and these are more common with the higher dose required for treatment Reversible elevations in liver enzymes have been reported The safety of atovaquone in pregnancy is unknown Plasma concentrations of atovaquone are decreased about 50% by coadministration of tetracycline or rifampin 9 Antibiotics A number of antibacterials in addition to the folate antagonists and sulfonamides are modestly active antimalarials They may inhibit protein synthesis or other functions in two plasmodial prokaryote-like organelles, the mitochondrion and the apicoplast None of the antibiotics should be used as single agents for the treatment of malaria because their action is much slower than those of standard antimalarials Tetracycline and doxycycline are active against asexual erythrocytic forms of all human malaria parasites They are not active against liver stages Doxycycline is commonly used in the treatment of falciparum malaria in conjunction with quinidine or quinine, allowing a shorter and better-tolerated course of those drugs Doxycycline has also become a standard chemoprophylactic drug, especially for use in areas of southeast Asia with high rates of resistance to other antimalarials, including mefloquine Doxycycline side effects include gastrointestinal symptoms, candidal vaginitis, and photosensitivity The drug should be taken while upright with a large amount of water to avoid esophageal irritation Its safety in long-term chemoprophylaxis has not been extensively evaluated Clindamycin is also slowly active against asexual erythrocytic forms and can be used in conjunction with quinine or quinidine in those for whom doxycycline is not recommended, such as children and pregnant women The most common toxicities with clindamycin are gastrointestinal Azithromycin also has antimalarial activity and is now under study as an alternative chemoprophylactic drug
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10 Halofantrine and lumefantrine Halofantrine hydrochloride, a phenanthrene-methanol related to quinine, is effective against erythrocytic (but not other) stages of all four human malaria species Oral absorption is variable and is enhanced with food Because of toxicity concerns, it should not be taken with meals Halofantrine is not available in the United States, but it is widely available in malaria-endemic countries It is rapidly effective against most chloroquineresistant strains of P falciparum, but its use is limited by irregular absorption and cardiac toxicity Cross-resistance with mefloquine may occur As treatment for falciparum malaria, halofantrine is given orally in three 500-mg doses at 6-hour intervals, and this course is repeated in 1 week for nonimmune individuals Because of toxicity concerns and irregular absorption, halofantrine should not be used for chemoprophylaxis Halofantrine is generally well tolerated The most common adverse effects are abdominal pain, diarrhea, vomiting, cough, rash, headache, pruritus, and elevated liver enzymes Of greater concern, the drug alters cardiac conduction, with dose-related prolongation of QT and PR intervals This effect is seen with standard doses and is worsened by prior mefloquine therapy Rare instances of dangerous arrhythmias and some deaths have been reported The drug is contraindicated in patients with cardiac conduction defects and should not be used in those who have recently taken mefloquine It is also contraindicated in pregnancy Lumefantrine, an aryl alcohol related to halofantrine, is available only as a fixed-dose combination with artemether (Coartem or Riamet) The half-life of lumefantrine, when used in combination, is 45 hours As with halofantrine, oral absorption is highly variable and improved when the drug is taken with food Use of Coartem with a fatty meal is recommended Coartem is highly effective for the treatment of falciparum malaria, but it is expensive and requires twicedaily dosing Despite these limitations, due to its reliable efficacy against falciparum malaria, Coartem has recently been selected as the first-line therapy for malaria in many African countries, although implementation of this change has been slow Coartem is well tolerated; toxicities include headache, dizziness, loss of appetite, gastrointestinal symptoms, and palpitations Importantly, Coartem does not appear to cause the cardiac toxicity seen with halofantrine
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