Antimalarials Flashcards
Clinical cure is
Getting rid of symptoms by eliminating blood schizonts
Radical cure means
Eliminating all plasmodia, both in the blood and liver stage
Required for ovale and vivax
Only the tissue schizonticide primaquine can provide a radical cure for these two.
P. falciparum
Most common and also most lethal form of malaria
Fever recurs every 3rd day
Can cause cerebral malaria by clogging small blood vessels in brain
No secondary tissue forms (radical cure with blood schizonticide)
P. vivax
Benign tertian malaria
Has secondary tissue form (hypnozoites) —> relapses
P. ovale
Rare
has hypozoite as well
P. malaria
Rare, no secondary tissue form
Three guiding factors for malaria treatment
- What plasmodium species?
- Clinical status of the patient (complicated or uncomplicated? Oral v Parenteral)
- Drug susceptibility of infecting parasites? Travel Hx and whether they were on prophylaxis
DOC* blood schizonticide for malaria
Chloroquine (Aralen) - declining in use b/c of resistance
For the treatment of chloroquine-resistant malaria:
DOC:
ACT drug AND either Atovoquone/proguanil (Malarone) or Lumefantrine (Coartem)
Next:
Quinine AND either doxycycline, tetracycline, or clindamycin
ACT + mefloquine
ACT + sulfadoxine-pyrimethamine (Fandisar)
Chloroquine MOA
Actively concentrated within plasmodia food vacuole —> interferes with lysosomal degradation of hemoglobin
Oral, well absorbed (though inhibited by Mg2+ and Ca2+)
Accumulates in melanin-rich tissues (skin, retina)
Metabolized by liver, substrate of CYP3A4
Can be used once weekly for prophylaxis b/c long duration of action
Chloroquine toxicity
Retinal and corneal toxicity
Hemolysis - caution in G6PD deficient patients
Increased risk for QT prolongation
Contraindicated for pt with psoriasis and porphyria (b/c increases attacks)
ACT drugs
Artemisinins: Artesunate and Artemether
Almost TOO good - work really well and eliminated really quickly, therefore high risk for resistance so ALWAYS use in combo
Cannot be obtained INDIVIDUALLY in the US but CDC has some
Artemisinin Combination Treatment (ACT)
NEVER monotherapy
DOC: Artesunate + Atovoquone-proguanil (malarone)
Artemether + lumefantrine (coartem)
Drug of last resort: Artesunate + mefloquine
In pregancy: Artesunate + sulfadoxine-pyrimethamine (Fansidar)
Sulfadoxine and proguanil both work on the same pathway as sulfa drugs
PABA in folate metabolism
Atovaquone + proguanil (Malarone)
Atovaquone - interferes with mitochondrial electron transport, ATP, and pyramiding biosynthesis
Proguanil - prodrug that is a folate reductase inhibitor
Synergistic combo - great in areas of chloroquine resistance
Combined with Artesunate for rapid clearance and decrease in resistance
Caution when used by pregnant women (need leucovorin supplement)
Lumefantrine (Coartem)
Given in combo with Artemether
Long-acting, oral
Toxicity - headache in 56%, QT prolongation
Quinine and Quinidine Gluconate
Quinidine (given IV) is a stereoisomers of quinine (oral)
An option for treatment of complicated, chloroquine-resistant malaria
Combine with doxy, tetracycline, or clindamycin to reduce the length of treatment
VERY toxic (narrow margin between therapeutic and toxic dose)
Quinine toxicity
Cinchonism - tinnitus, headache, dizziness, flushing, visual disturbances Antiarrhythmic agent - class1A QT elongation Diarrhea Hemolysis in G6PD deficient patients
Antibiotics for malaria treatment
Tetracycline, doxycycline, clindamycin
Not for use in pregnant women or children
Combined with quinidine gluconate or quinine for the treatment of complicated, chloroquine-resistant malaria
Tetracyclines more effective than clindamycin
Doxy can be used for prophylaxis (daily)
Mefloquine (Lariam)
Used for treatment of chloroquine-resistant malaria
Orally, very slowly excreted (single dose treatment)
TOXIC - depression of the myocardium, seizures, aggravate latent psychoses
DO NOT USE in any patient with mental illness or epilepsy
Pyrimethamine plus sulfadoxine (Fansidar)
Used for empirical treatment and preventative intermittent therapy in PREGNANT WOMEN
Combined with Artesunate
Potential for toxicity and allergic reactions like other sulfas
Not available in US
Primaquine
The ONLY tissue schizonticide, for use vs. vivax or ovale to achieve radical cure (terminal prophylaxis)
Must also use with blood schizonticide to treat symptoms (won’t suppress disease once developed)
Primaquine contraindications and toxicities
Contra in SLE or rheumatoid arthritis —> granulocytes Elia
Hemolytic anemia in G6PD deficiency (use at low dose for longer period)
DO NOT use in pregnancy because you don’t know the G6PD status of the fetus
