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Chloroquine

Spectrum activity
Antimalaria (drug of choice for non-falciparum atau falciparum sensitive strain) Highly effective : blood shizonticide Moderate : gamatocide of P. vivax, P. malariae, P. ovale Not for liver stage Amebicides Malaria (drug of choice for treatment and prophylaxis) Terkonsentrasi di parasite food vacuole inhibit polymerasi heme menjadi hemozoinfree heme parasite toxicity Pruritus, nausea, vomit, abdominal pain, headahe, anorexia, blurred vision, urticaria. Retinopathy, hair loss, photosensitivity, tinnitus, myopathy (long-term therapy). Psychosis, seizures, leucopenia and rarely aplastic anaemia. Psoriasis & phorphyria (karena bisa memperparah) Retinal /visual field abnormalities Myopathy

Amodiaquine
Antimalaria (sama dengan chloroquine, namun bisa u/ P. falciparum yang resistent terhadap chloroquine)

Primaquine
Antimalaria (drug of choice for eradication of dormant live form of P. vivax dan P. ovale) Hepatic stage of all malaria Schizonticidal for P. vivax dan P. ovale (most important , eradicate hypnozoit) Gametocidal againts the 4 human malaria species Radical treatment and Prophyilaxis of vivax and ovale malaria Pneumocystis jiroveci infetion disrupting mitochondria and binding to DNA bacteria interfering with the electron transport in the parasite generating reactive oxygen species toxicity hemolisis Infrequently (when taken w/ higher dose or in empty stomach) nausea, epigastric pain, abdominal cramps, headache More serious (rare) leukopenia, agranulocytosis, cardiac arythmia History of granoloytopenia or methemaglobinemia G6PD deficiency or other metabolic defect Pregnancy G6PD deficiency; pregnancy; NADH methaemoglobin reductase deficient patients. Withdraw treatment if signs of haemolysis or methaemogloinaemia occur Kontraindikasi untuk anak < 1 tahun

Indikasi MOA Side Effect

Malaria (tapi tdk untuk prophylaxis karena efek samping yang berbahaya dlm penggunaan jangka panjang) Binds to free heme menghambat heme polymerase activity free heme toxic , distrup membran function Kelainan darah (agranulocytosis, aplastic anemia), gangguan pencernaan, gangguan pengelihatan, gatal-gatal, neuromyopathy

Contraindicati on Precaution Use Pediatric Elderly

hypersensitivity to amodiaquine in persons with hepatic disorders for chemoprophylaxis.

Considered safe for young childern Adjustment dose Adjustment dose

Pregnancy Renal failure Liver dysfuntion Life cycle

Kategori C, pada hewan bersifat teratogenik, tp belum dicoba pada manusia Dapat digunakan dengan pertimbangan Used with caution Not advisable Absorption: Rapid and complete (oral); rapid (IM/SC). Distribution: Widely distributed; high concentrations in kidneys, liver, lungs and spleen; crosses the placenta; enters breast milk. Metabolism: Extensively hepatic; converted to monodesethylchloroquine. Excretion: Urine (as unchanged drug and metabolite). Low cost

Kategori C, Amodiaquine should not be used during pregnancy unless clearly necessary Used with caution Used with caution, karena amodiaquine dapat terkonsentrasi di liver

Dosis yang digunakan harus diperhitungkan, dimulai dari dosis terendah, mempertimbangkan kemungkinan yang lebih besar terjadinya gangguan fungsi liver, ginjal, atau jantung.. Sebaiknya dihindari (karena status G6PD pada janin tidak diketahui) Use with caution No direct toxicity Absorption: mudah diserap di GI-tract, peak plasma concentrations after 1-2 hr (oral). Distribution: tersebar di seluruh jaringan. Protein-binding: 98% Metabolism: Hepatic; converted to carboxyprimaquine (major metabolite). Excretion: Urine (as unchanged drug); 3-6 hr (elimination half-life)

Specific advantage

Weekly dose starting one week before exposure and continuing while at risk then for 4 weeks after leaving malarious area. Few side effects (headaches, nausea, mouth ulcers). Safe for children and for pregnant or lactating women. Less effective (70%) in Africa and South East Asia. Bitter taste. (Rare) psychological side effects (1 in 10,000). May worsen psoriasis More complicated schedule (chloroquine weekly, proguanil daily)

More palatable than chloroquine, lebih mudah digunakan pada anak-anak Bisa menggantikan chloroquin pada daerah yang mengalami resistensi.

Good choice for shorter trips: only have to

take the medicine for 7 days after traveling rather than 4 weeks Good for last-minute travelers because the drug is started 1-2 days before traveling

Specific disadvantage

Severe toxicity

Cannot be used in patients who have not There are costs and delays associated with
getting a G6PD test done; however, it only has to be done once been tested for G6PD deficiency

Drug interaction

Andiarrheal kaolin, calcium or magnesium containing antacide interfere absorption chloroquine Penggunaan dgn phenylbutazone memicu dermatitis antagonis neostigmine dan pyridostigmine reduces bioavailability of ampicillin Cimetidine inhibits metabolism of chloroquine

Antacids containing products, e.g. magnesium trisilicate and kaolin are known to decrease the gastrointestinal absorption of Amodiaquine, meningkatkan kadar chlorpromazine di darah.

Primaquine may inhibit metabolism of chloroquine. Avoid ethanol. Potentially Fatal: Mepacrine may potentiate toxicity of primaquine

Quinine & Quinidine


Spectrum activity
Antimalaria 1st line therapy for falciparum malaria (terutama pada kasus parah) Shizontocide againts 4 species malaria Gametocidal for P. vivax dan P. ovale, namun tidak untuk P. falciparum Not for liver stage parasite Malaria falciparum Babesiosis Accumulate in acidic food vacuoles of parasite Inhibits heme polymerase --> block Hb digestion --> heme accumulation --> toxicity Tinnitus, headache, nausea, dizziness, flushing, dan visual disturbance kumpulan gejala yg dinamakan cinchonism Hematologic abnormalities hemolisis, agranulositosis, leuko/thrombocytopenia Hypoglycemia (krn meng-induce insulin) Photosensitivity, arrythmias (IV use) Pasien dengan gangguan visual atau auditory Hypersensitivity Myesthenia gravis AV block Lactation. CV diseases; G6PD deficient individuals. Penggunaannya aman dan ampuh pada anak-anak Belum diuji secara sistematis Kategori C : Quinine can be used in pregnancy, but one should be watchful about hypoglycemia. Dosis quinine harus dikurangi pada RF jika serum creatinin > 3mg% Used with caution Absorption: hampirdiserap komplit via GI tract Distribution: distribusi ke seluruh jaringan kecuali otak, protein binding 82-92% Metabolism: hepatic via hydroxylation Excretion: Urine (as unchanged drug and metabolite). Slow to develop resistance expensive time consuming to produce

Mefloquine
Antimalaria Strong blood schizonticidal againt P. falciparum and P. vivax Not active againts hepatic stage or gametocyte

Indikasi MOA

Side Effect

Contraindication

Chemoprophylaxis for malaria Treatment for most falciparum malaria Same with quinine and chloroquine Membentuk complex dengan free heme yang bersifat toxic interact with oter plasmodial component swelling of plasmodium food vacuole Frequent SE : dizziness, mild to moderate nausea, vomiting, diarrhoea and abdominal pain Neuropsychiatric adverse reaction (sleep and behavioral disturbance, seizure, psyhosis) Altered cardiac conduction (bradycardi dan arrythmia) history of allergy to mefloquine, history of severe neuropsychiatric disease, epilepsi, arythmia, cardiac conduction defect penggunaan bersamaan dengan quinine, quinidine, atau halofantrine Now considered safe in young childern, dosis untuk anak diperkirakan dari dosis orang dewasa Dosis adjustment Kategori B mefloquine is contraindicated in the first trimester of pregnancy Dapat digunakan karena hanya sedikit eksresi lewat urine Not recomended the elimination of Mefloquine may be prolonged, leading to higher plasma levels and a higher risk of adverse reactions Absorption: well absorp via GI tract, meningkat dengan adanya makanan Distribution: volume distribusi 20L/Kg, extensive tissue distribution Metabolism: hepatic via cytohrome P450 Excretion: terutama via bile dan feces Single oral dose Cost effective High risk of adverse reaction (28-95%) Tidak baik untuk perjalanan mendadak, krn mefloquine sbgai prophylaxis harus diminum 2 minggu sebelum berangkat. a blood thinner such as warfarin (Coumadin); ketoconazole (Nizoral); rifabutin (Mycobutin); rifampin (Rifadin, Rifater, Rifamate, Rimactane); tetracycline (Brodspec, Panmycin, Sumycin, Tetracap); or metoclopramide (Reglan).

Precaution Use Pediatric Elderly Pregnancy Renal failure Liver dysfuntion Life cycle

Specific advantage Specific disadvantage Drug interaction

Alumunium-containing antacide : menghambat absorpsi quinine Raise plasma level of warfarin dan digoxin Rifampicin accelerates quinine clearance; cimetidine inhibits quinine metabolism; quinine may enhance hypoglycaemic effects of oral antidiabetics