Pharmacology AntiMalarials

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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.
  7. 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)
  8. 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.
  9. Mefloquine (general info)
    • Quinoloine class
    • potent blood schizonticide
    • used for chloroquine-resistant parasites
    • prophylaxis
    • rare resistant cases (cross resistance with quinine but not chloroquine)
  10. 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
  11. 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
  12. Primaquine (side effects and contraindications)
    • Side effects: nausea, HA, ab pain,
    • Rare: arrhythmias, agranulocytosis, leucopenia
    • Contraindications: patients with G6PD deficiency
  13. 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
  14. 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%
  15. 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
  16. 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
  17. Sulfonamide and sulfones
    • active against erythrocytic schizonet
    • not used alone as anti-malarial
  18. 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 .
  19. 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
  20. Clindamycin
    • active against erythrocyte schizont
    • use in combo with quinine or quindine
  21. Azithromycin
    antimalarial activity is under investigation
  22. Artemisinin
    • Active component in chinese herbal
    • insoluble, can be used orally
    • cant be used in chemoprophylaxis
    • irreversible neurotoxicity in animals
    • avoid during pregnancy
  23. 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
  24. 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
Card Set
Pharmacology AntiMalarials
Pharmacology, Antimalarials