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23 Cards in this Set
- Front
- Back
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What is the life cycle of malaria?
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Sporozoites in fly saliva
travel to hepatocytes and mature into schizonts Schizonts rupture releasing merozoites merozoites invade RBCs Merozoites rupture and release from RBCs |
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What are the three categorical uses of antimalarials?
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Prophylaxis
Treatment Cure |
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What are the two kinds of prophylaxis?
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Causal prophylaxis: kill in liver stage
Supressive prophylaxis: kills or suppresses early in erythrocytic stage |
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What are the Cinchona alkaloids?
What is their mechanism of action? |
Quinine
Quinidine Mechanism may be the same as chloroquine: drug accumulates in the acid vacuole of the parasite, becomes protonated and trapped and interferes with heme polymerase. Toxic heme accumulates to levels that kill the parasite. |
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How do we use Quinine?
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Oral: uncomplicated MDR malaria, usu in combination with doxycycline or Fansidar.
IV: severe and complicated malaria tx of nocturnal leg cramps |
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How do we use quinidine?
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parenteral tx of SEVERE and COMPLICATED P Falciparum.
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What are the adverse effects of the Cinchona alkaloids?
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CINCHONISM
QT prolongation, torsade de pointes, hypotension Hypoglycemia Drug induced ITP (quinine) Blackwater fever |
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What is CINCHONISM?
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adverse effect of cinchona alkaloids
Tinnitus, blurred vision, headache, nausea/vomiting, dysphoria |
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What is BLACKWATER FEVER?
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Triad of massive hemolysis, hemoglobinemia, and hemoglobinuria
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What is Chloroquine and what makes it unique?
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Chloroquine is a blood schizonticide that revolutionized malaria tx and prevention (4-aminoquinolone)
Unlike quinine, tolerability was good Now there is widespread resistance, so it is used primarily for non-falcip malaria and tx of autoimmune diseases |
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What are the side effects of chloroquine?
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DNV anorexia and abd cramps
seizures, nerve type deafness, psychiatric disturbances Retinal damage in pts recieving long term or high dose therapy |
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What is FANSIDAR? How does it work?
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A synergistic combination of Pyrimethamine (inhibits dihydrofolate reductase) and sulfadoxine (inhibits conversion of PABA by dihydropteroate synthetase).
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What is the problem with Fansidar?
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Although useful in tx of chloroquine resistant P Falcip, resistance develops rapidly when widely used.
Side effects are referable to sulfonamide component ( blood dyscrasia [STEVENS JOHNSON SYNDROME] and hypersensitivity) No longer recommended as a prophylactic drug. |
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What drug was developed to replace chloroquine in chloroquine resistant areas?
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Mefloquine
resistance (efflux pump) is a problem in Thailand. Known for associated neuropsychiatric disorders, good for prohylaxis (not causal) |
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What are the side effects with mefloquine?
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dizziness, n/v , sleep disturbance
seizures sinus bradycardia- slight QT prolongation |
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What is wierd about halofantrine?
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Mechanism unknown, poorly and erratically absorbed from GI, YET it is NOT recommended to be given with food bc of CARDIOTOXICITY (yikes)
Prolongation of QT and arrythmia-associated deaths reported |
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What is the antibiotic used for malaria prophylaxis?
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DOXYCYLINE (and tetracycline) have antiplasmodial effects.
They are slow acting and cannot be used as single agents. |
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Why is doxy difficult to use as a prophylaxis?
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Daily dosing makes compliance decrease aswell as 4 weeks of drug administration is necessary after leaving the endemic area (bc it isn't CAUSALLY pophylactic)
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What is the mechanism of doxy?
What are the uses? |
Inhibition of prot synth by inhibition of binding of aa-t-RNA
Used for prophylaxis in mefloquine resistant areas and comb tx w quinine for MDR UNcomplicated malaria. |
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What are the adverse efffects of doxy?
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Nausea
Sun sensitivity Vaginitis Esophageal ulcers Contraindicated in kids and preggos (its a tetracycline!) |
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Why is primaquine unique?
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bc it affects ALL specied of Plasmodia.
Compliance is critical (one missed dose= failure) Hemolysis in G6PD deficiency. Methmoglobinemia |
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What is Malarone?
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Synergistic combination of Atovaquone-Proguanil.
Safe use in kids and preggos (proguanil) Both agents are CAUSAL prophylactics |
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What is the fastest of the antimalarials?
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Artemisinin derivatives (ENDOPEROXIDES)
H2O soluble, administerable via any route, including rectally (yummy) Neurotoxicity observed in animals |
