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Mefloquine Proguanil
Mefloquine is structurally similar to quinine. It is Proguanil marketed in combination with atovaquone
used for treatment or prophylaxis of drug-resistant ma- is used for both the treatment of uncomplicated P. falci-
laria. It may have cardiac depressant effects and antifi- parum and prophylaxis of mild chloroquine-resistant
brillary activity, and may result in marked gastrointesti- malaria. The most common AEs reported in 110% of pa-
nal or CNS AEs and is, therefore, not recommended as tients taking atovaquone/proguanil for treatment of ma-
first-line treatment; nausea, strange dreams, seizures laria are abdominal pain, nausea, vomiting, and head-
(rare), and psychosis may also occur [12]. Severe CNS ache in adults, and vomiting in children; for prophylaxis
events requiring hospitalization (e.g. seizures and hallu- of malaria AEs include headache and abdominal pain
cinations) occur in 1:10,000 patients taking mefloquine and vomiting in children. It is well tolerated, and al-
as chemoprophylaxis. However, milder CNS events (e.g. though oral aphthous ulcerations are not uncommon,
dizziness, headache, insomnia, and vivid dreams) are they are rarely severe enough to warrant discontinuing
more frequently observed, occurring in up to 25% of pa- this medication. Proguanil is considered safe during
tients. The higher incidence of AEs observed when the pregnancy and breastfeeding, but insufficient drug is ex-
drug is used at the higher doses needed for malaria treat- creted in the milk to protect a breastfed infant [15].
ment implies a dose effect [13]. It is contraindicated in
hypersensitivity; epilepsy or seizure disorder; severe psy- Diaminopyrimidines (Antifolates)
chiatric disorder, and in patients with a diagnosis or treat- Pyrimethamine-sulfadoxine can be used to treat ma-
ment for irregular heartbeat. laria. It is no longer considered a first-line agent for pro-
phylaxis because of the AE profile. Co-trimoxazole can
Amodiaquine be used in combination with rifampicin and isoniazid in
Amodiaquine is thought to have the same mechanism resistant P. falciparum [16]. Antimalarial doses of pyri-
of action as its analogue chloroquine. Hepatitis and agran- methamine alone cause little toxicity except occasional
ulocytosis were seen in patients taking amodiaquine for skin rashes and decreased hematopoiesis. Excessive doses
prophylaxis, and the drug is no longer recommended for produce megaloblastic anemia, resembling folate defi-
this indication. Amodiaquine-quinoneimine can be gen- ciency, that responds readily to drug withdrawal or treat-
erated from amodiaquine both spontaneously, when the ment with folinic acid. It causes severe to even fetal cuta-
drugs is in aqueous solution, and as a result of enzyme ac- neous reactions, such as erythema multiforme, Stevens-
tivity. The quinoneimine is highly reactive and haptenates Johnson syndrome, and toxic epidermal necrolysis,
proteins, generating antigen to which an immune response dermatitis, serum sickness-type reactions, and hepatitis.
may be mounted. Repeated exposure to this antigen may Toxic sulfamethoxazole metabolites may elicit hypersen-
be important in the generation of organ damage [3]. sitivity reactions. Trimethoprim can inhibit renal creati-
nine secretion, leading to high serum creatinine levels.
Doxycycline Trimethoprim also inhibits dihydrofolate reductase,
Doxycycline is used as part of combination therapy or causing decreased dopamine production, which may lead
as prophylaxis of malaria. Photosensitivity may occur to parkinsonian symptoms [17]. The drug is contraindi-
with prolonged exposure to sunlight or tanning equip- cated in persons with a history of intolerance to sulfon-
ment. In renal impairment, dose reductions are indicat- amides and in infants ^2 months [18].
ed. Doxycycline may cause gastrointestinal upset and
rarely esophageal ulceration. It is photosensitizing and Quinine
may make the skin more susceptible to sunburns. Al- Quinine sulfate is used for malaria treatment only, has
though tetracyclines and other antibiotics have been cit- no role in prophylaxis and is used with a second agent in
ed as a cause of oral contraceptive failure [8, 14], a recent drug-resistant P. falciparum. Hemolytic anemia may oc-
case-control analysis failed to demonstrate any signifi- cur in patients with G6PD deficiency.
References
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