What do quinolines do?
Impairs intra-parasitic heme polymerization into hemozoin. Parasites digesting hemoglobin need to compartmentalize their waste products, if they can’t, then they die by their own waste.
Thus this works only on life cycle stages that consume hemoglobin
Examples of quinolines
Quinine Quinidine Chloroquine Hydroxychloroquine (Plaquinil) (although this is used more in rheumatology as an antimalarial) Mefloquine Primaquine Lumefantrine
What does chloroquine not work on?
P falciparum has a PfCRT ( P falciparum chloroquine resistance transporter) that pumps chloroquine out of the digestive vacuole
For quinolines, which are prophylactic vs therapeutic?
Chloroquine and mefloquine are the only ones for prophylaxis.
Rest are therapeutic, although Primaquine can be used as a “radical cure”
What quinines CAN be used to fight P Falciparum since we can’t use chloroquine?
Severe: Parenteral quinine/quinidine (IV not available in U.S.)
Uncomplicated: Oral quinine + doxy/clindamycin
Chloroquine can still be used in places that don’t have resistance (central America, Haiti, DR)
What do we worry about with quinine and quinidine?
Quinine can cause cinchonism (tinnitus, headache, nausea, bitter taste)
Quinidine is an older generation antiarrythic. The dose we need for antimalarial status causes prolonged corrected QT intervals, so only use this in ICU settings where heart monitors are available.
Both can induce insulin secretion with a resultant hypoglycemia
What do we tend to use chloroquine for?
P falciparum in Central America, Haiti, DR
P.vivax, Povale and P.malariae in most locations
When do we give mefloquine and why is it so great for patients?
They can be dumb and forget their meds (3 week half life)
We use it for chloroquine resistant P. falciparum. Also a prophylactic
What side effects and contraindications for mefloquine?
- Cardiotoxic if used with quinine/quinidine/halofantrine (kinda dumb since quinidine already is cardiotoxic alone)
- Neuropsychiatric side effects at treatment
Who do we give mefloquine to?
Highly effective but it has a lot of side effect damage.
Only consider for pregnant women (category B), long term travelers who want to save money, and young children (adherence) and usually only as prophylaxis
What is resistant to Mefloquine?
P. Falciparum (what a dick, seriously dude, stop it)
Multidrug resistance protein-1 (PfMDR1). Efflux pump for mefloquine, quinine, quinidine. And to boot, this has polymorphisms, so we get varied phenotypes. Hooray.
What do we give primaquine for?
Prevention of relapses “only for persons who have had prolonged exposure in malaria-endemic areas (missionaries, Peace Corps volunteers, etc.) - Force Health Protection
What big concern do we have for Primaquine?
Test for G6PD deficiency to avoid hemolytic reactions!
What antifolates and sulfas do we use?
Antifolate - Proguanil, pyrimethamine
Sulfa - Suldadoxine, trimethoprim
How do antifolates and sulfas work?
Inhibit dihydropterate synthase/reductase to stop nucleic acid synthesis.