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Chloroquine (general info) (4-aminoquinolines)
- Drug of choice for non-resistance forms of plasmodia
- Effective blood schizonticide and gametocide (not for P. falciparum)
- T1/2: 3-5 days (slow release from tissue and slow metabolism of drug)
- Phosphate salt form for oral use
- completely and rapidly absorbed by GI tract
- Max plasma conc 3 hr
- widely distributed in all tissue
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Chloroquine (clinical use)
- prophylaxis
- used against non-falciparum and non-resistant falciparum
- fever termination in 24-48 h
- clearance of parasitaemia 42-72 h
- widely used in developing countries
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Chloroquine (Mechanism of action)
- This drug stops Heme from being turned into hemozoin by the parasite. This causes a build up of heme which is toxic to the parasite.
- Basically blocks the HISrich protein and lipid polymerization
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Chloroquine (adverse effects)
- Common: pruritus among africans
- Uncommon: N/V, ab pain, HA, anorexia, malaise, blurred vision, urticaria
- Rare: hemolysis during G6PD deficiency, impaired hearing, confusion, psychosis, seizures, agranulocytosis, exfoliative dermatitis, alopecia, hair bleaching, hypotension
- Long Term (for rheumatoid patients): irreversible ototoxicity, retinopathy, myopathy and peripheral neuropathy
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Chloroquine (contraindications)
- Do not use in: psoriasis, retinal and visual field abnormalities and myopahty, in liver, neurological and hematological disorders
- Drugs that interfere with absorption: antidiarrheal kaolin, Ca+ and Mg+ antacids
- This is safe during pregnancy
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Amodiaquine
- Similar to chloroquine but limited due to toxicity
- used for chloroquine resistant P. falciparum
- Toxicities: agranulocytosis, hepatotoxicity, aplastic anemia
- Contraindications: long term use due to increased toxicity.
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Quinine and Quinidine (general info)
- quinoline class of drug
- potent against erythrocytic plasmodia forms
- Not active against hepatic parasites
- not gametocidal against falciparum
- resistance uncommon but increaseing
- highly protein bound
- T1/2: 10 hr (much shorter than chloroquine)
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Quinine and quinidine (side effects and chontraindications)
- Side effects: cinchonism (flushed and sweaty, ringing in ears (tinnitus), blurred vision, impaired hearing, confusion, reversible high frequency hearing loss, headache, ab pain, rashes), cardiac dysrrhythmias and hypotension
- Contraindication: co administration with mefloquine, and patient on digoxin or warfarin
- Not generally used in chemoprophylaxis due to toxic effects.
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Mefloquine (general info)
- Quinoloine class
- potent blood schizonticide
- used for chloroquine-resistant parasites
- prophylaxis
- rare resistant cases (cross resistance with quinine but not chloroquine)
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Mefloquine (side effects and contraindications)
- side effects: N, ab pain, dizziness, sleep and behavioral disturbances
- Contraindications: co admin with quinine or quinidine, patients with seizures, psychosis, arrhythmias, and children under 5 kg
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Primaquine (8-aminoquinolines) (general info)
- Only agent effective against hepatic stages of P. vivax and P. ovale
- effective gametocide for all plasmodial forms
- used as PH4 salt
- Used in chemoprophylaxis
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Primaquine (side effects and contraindications)
- Side effects: nausea, HA, ab pain,
- Rare: arrhythmias, agranulocytosis, leucopenia
- Contraindications: patients with G6PD deficiency
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Atovaquone (component of Malarone) (general info)
- oral administration
- for chloroquine-resistant parasites
- disrupts mitochondrial electron transport
- active against hepatic and erythrocytic forms of P. falciparum but NOT vivax and ovale.
- Low oral bioavailability which is increased with fatty foods
- T1/2: 2-3 days
- Used for treatment and prophylaxis
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Atovaquone (side effects and contraindications)
- Side effects: generally well tolerated, ab pain, n/v, ha, rash, reversible increase of liver enzymes
- Contraindications: unknow if safe during pregnancy, tetracyclin or rifampin decrease plasma conc by 50%
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Pyrimethamine
- folate metabolism antagonists
- active against erythrocytic forms of all 4 species
- not effective against gametocyts and persistent liver stage
- plasma peak 2-6 h
- T1/2: 3.5 h
- Side effects: Gi disturbance,rash and urticaria, teratogenic
- Not effective against vivax or ovale
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Proquanil (component of malarone)
- folate metabolism antagonist
- active against erythrocytic forms of all 4 speciesnot effective against gametocyts and persistent liver stage
- plasma peak 5 hr
- T1/2 16 h
- cycloguanil is active metabolite
- side effect: mouth ulcers and alopecia
- Not effective against vivax or ovale
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Sulfonamide and sulfones
- active against erythrocytic schizonet
- not used alone as anti-malarial
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Fansidar
- Folic acid metabolism inhibitor
- Combo of sulfadoxine and pyrimethamine
- Inhibits 2 points 1st and 3 step of folic acid synthesis. Synergism
- 1st line therapy for toxoplasmosis, but not recommended for malaria due to resistance
- Side effects: ab pain, Gi distress, N/v, dizziness, fatigue, megaloblastic anemia, skin photosensitivity
- Contraindications: G6PD deficiency and folid acid anemia, porphyria, sever renal disease, late pregnancy and lactation .
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Doxycyline
- active against erythrocytic schizont
- used in combo with quinine or quinidine
- used as prophylactic in south east asia
- side effects: gi symptoms, cadidal vaginitis, photosensitivity
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Clindamycin
- active against erythrocyte schizont
- use in combo with quinine or quindine
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Azithromycin
antimalarial activity is under investigation
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Artemisinin
- Active component in chinese herbal
- insoluble, can be used orally
- cant be used in chemoprophylaxis
- irreversible neurotoxicity in animals
- avoid during pregnancy
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Artesunate
- artemisinin derivative
- water soluble
- oral, IM or rectal
- peak plasma 1-2 h
- T1/2 3 hr by oral
- Not in US, can only get through CDC
- Active against erythrocyte schizonts
- Anti malarial activity due to free radical production
- Active against multi-drug resistant malaria
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Artemether
- Artemisinin derivative
- lipid soluble
- oral, IM or rectal
- peak plasma 1-2 hr
- T1/2: 3 h
- not available in US
- only active against blood stage
- anti-malarial activity due to free radical production
- multi-drug resistan malaria
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