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23 Cards in this Set

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What is the life cycle of malaria?
Sporozoites in fly saliva
travel to hepatocytes and mature into schizonts
Schizonts rupture releasing merozoites
merozoites invade RBCs
Merozoites rupture and release from RBCs
What are the three categorical uses of antimalarials?
Prophylaxis

Treatment

Cure
What are the two kinds of prophylaxis?
Causal prophylaxis: kill in liver stage
Supressive prophylaxis: kills or suppresses early in erythrocytic stage
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.
How do we use Quinine?
Oral: uncomplicated MDR malaria, usu in combination with doxycycline or Fansidar.

IV: severe and complicated malaria

tx of nocturnal leg cramps
How do we use quinidine?
parenteral tx of SEVERE and COMPLICATED P Falciparum.
What are the adverse effects of the Cinchona alkaloids?
CINCHONISM
QT prolongation, torsade de pointes, hypotension
Hypoglycemia
Drug induced ITP (quinine)
Blackwater fever
What is CINCHONISM?
adverse effect of cinchona alkaloids
Tinnitus, blurred vision, headache, nausea/vomiting, dysphoria
What is BLACKWATER FEVER?
Triad of massive hemolysis, hemoglobinemia, and hemoglobinuria
What is Chloroquine and what makes it unique?
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
What are the side effects of chloroquine?
DNV anorexia and abd cramps
seizures, nerve type deafness, psychiatric disturbances
Retinal damage in pts recieving long term or high dose therapy
What is FANSIDAR? How does it work?
A synergistic combination of Pyrimethamine (inhibits dihydrofolate reductase) and sulfadoxine (inhibits conversion of PABA by dihydropteroate synthetase).
What is the problem with Fansidar?
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.
What drug was developed to replace chloroquine in chloroquine resistant areas?
Mefloquine
resistance (efflux pump) is a problem in Thailand. Known for associated neuropsychiatric disorders, good for prohylaxis (not causal)
What are the side effects with mefloquine?
dizziness, n/v , sleep disturbance
seizures
sinus bradycardia- slight QT prolongation
What is wierd about halofantrine?
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
What is the antibiotic used for malaria prophylaxis?
DOXYCYLINE (and tetracycline) have antiplasmodial effects.
They are slow acting and cannot be used as single agents.
Why is doxy difficult to use as a prophylaxis?
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)
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.
What are the adverse efffects of doxy?
Nausea
Sun sensitivity
Vaginitis
Esophageal ulcers
Contraindicated in kids and preggos (its a tetracycline!)
Why is primaquine unique?
bc it affects ALL specied of Plasmodia.
Compliance is critical (one missed dose= failure)
Hemolysis in G6PD deficiency.
Methmoglobinemia
What is Malarone?
Synergistic combination of Atovaquone-Proguanil.
Safe use in kids and preggos (proguanil)
Both agents are CAUSAL prophylactics
What is the fastest of the antimalarials?
Artemisinin derivatives (ENDOPEROXIDES)
H2O soluble, administerable via any route, including rectally (yummy)
Neurotoxicity observed in animals