Antimalarials Flashcards
which form of malaria have two types of stages/parasite forms to eliminate and why
- plasmodium vivax and ovale both have a dormant hepatic stage so both erythrocytic and hepatic parasites must be eliminated
- plasmodium falciparum and malariae only have erythrocytic parasites to eliminate
which form of malaria can have an incubation period that can last years
plasmodium malariae
symptoms of malaria
malaria paroxysm (sudden attack) - fever, anemia, splenomegaly, jaundice, hepatomegaly
which form of malaria is most severe and why
plasmodium falciparum –> cerebral malaria
- irritability, seizure, coma
- also respiratory distress syndrome, diarrhea, severe thrombocytopenia, spontaneous abortion, hypoglycemia
treatment of malaria should be guided by what
- species of infecting plasmodium
- clinical status of patients
- drug susceptibility of infecting parasites
major antimalarial drugs
CAM PADS Q
Chloroquine Quinine and Quinidine Mefloquine Primaquine Atovaquone Sulfadoxine-Pyrimethamine Doxycycline Artemisinins
clinical application of chloroquine
treatment and prophylaxis of plasmodium vivax and ovale
sensitive uncomplicated falciparum
MOA of chloroquine
prevents biocrystallization of hemoglobin breakdown product heme to non toxic hemozoin –> accumulation of heme –> lysis of parasite and RBC –> effective against blood parasites and not liver parasites
what is resistance against chloroquine
plasmodium falciparum – due to mutations in putative transporter, PfCRT
adverse effects of chloroquine
Pruritus (most common)
Hemolysis in G6PD deficiency
contraindications of chloroquine
patients with psoriasis or porphyria (precipitate attacks)
retinal or visual field abnormalities
what are quinine and quinidine used for
severe forms of plasmodium falciparum malaria
quinine is oral and quinidine is parenteral
mechanism of quinine and quinidine
depresses O2 uptake and carb metabolism –> intercalates into DNA –> disrupts parasites replication and transcription –> only good for blood parasites
adverse effects of quinine and quinidine
CHHHUBES
Cinchonism - tinnitus, visual probs, dizziness
Hypersensitivity - skin rash, urticaria
Hematological abnormalities
Hypoglycemia - stimulates insulin release
Uterine contractions
Blackwater fever - hemolysis and hemoglobinuria
ECG abnormalities - QT prolongation
Severe hypotension - too rapid IV infusion
contraindications of quinine and quinidine
- visual or auditory problem (cinchonism)
- cardiac abnormalities (ECG problems)
- raises levels of warfarin and digoxin
- reduced dose in renal insufficiency
- don’t use with mefloquine
MOA of Mefloquine and its clinical application
destruction of asexual blood forms of malarial pathogens
chemoprophylaxis in preggos in chloroquine resistant areas
what drug does mefloquine causes a resistant to
quinine
adverse effects of Mefloquine
Neurologic and psychiatric toxicities
Cardiac conduction defects
contraindications of Mefloquine
- Do not administer with quinine, quinidine, and halofantrine
- Patients with history of neurologic, psychiatric, and cardiac problems
drug of choice for dormant liver form of plasmodium vivax and ovale
primaquine
adverse effects of primaquine
Hemolysis
Methemoglobinemia
both especially in G6PD deficiency since primaquine further decreases available GSH by oxidizing it to GSSG
contraindication of primaquine
G6PD deficiency
Pregnancy - fetus is relatively G6PD deficient
what is Malarone
Atovaquone + Proguanil
MOA of malarone and clinical application (what is it again)
atovaquone + proguanil
disrupts mitochondrial electron transport –> used for plasmodium falciparum
contraindications of Malarone (name what it is)
Atovaquone + Proguanil
Pregnancy
inhibitors of folate synthesis used as antimalarials
Pyrimethamine
Proguanil
Sulfadoxine
MOA of the antimalarial inhibitor of folate synthesis
Pyrimethamine + Proguanil = inhibitor plasmodial dihydrofolate reductase
Sulfadoxine = inhibit dihydropteroate synthase
of the three antimalarial inhibitor of folate synthesis, which works weakly on hepatic forms
Proguanil
adverse effects of antimalarial inhibitor of folate synthesis (individually)
Pyrimathamine-Sulfadoxine: Erythema Multiforme, Stevens-Johnson, Toxic epidermal necrolysis
Proguanil: mouth ulcers, alopecia
Sulfadoxine: Hematological, GI, CNS, dermatologic, and renal toxicities
clinical application of doxycycline
prophylaxis for all form
treatment of p. falciparum
not used against liver stages
adverse effects of doxycycline and contraindications
- stunting of growth
- discoloration and hypoplasia of teeth
- fatal hepatoxicity in pregnancy
-don’t use in pregnancy and children under 8
types of artemisinins
artesunate
artemether
dihydroartemisinin
coartem
MOA of artemisinins
binds to iron –> breaks down peroxide bridges –> free radical generation -> damage parasitic protein
other antimalarials
Clindamycin
Halofantrine
Lumefantrine
adverse effects of halofantrine
teratogenic
when is mefloquine usually given
when chloroquine resistant especially in preggos
what is given as prophylaxis when chloroquine resistant
mefloquine, doxycycline, primaquine
