Malaria Drugs Flashcards
Quinine (Qualaquin)
Class: Quinolone derivitive
Mech: Accumulate in parasite’s food vacuole, disrupt heme polymerization to hemozoin, yielding oxidative damage to membranes and digestive proteases
Thera: Prophylaxis, treatment of acute malarial attacks
Important SE’s: Cinchonism, hypotension, hypoglycemia, abortion, arrhythmias
Misc: Also called quinidine (used in anti-arrhythmias)
Chloroquine (Aralen)
Class: Quinolone derivitive
Mech: Accumulate in parasite’s food vacuole, disrupt heme polymerization to hemozoin, yielding oxidative damage to membranes and digestive proteases
Thera: Prophylaxis, treatment of acute malarial attacks
Important SE’s: Itching (Africans), retinitis (rare)
Hydroxychloroquine (Plaquenil)
Class: Quinolone derivitive
Mech: Accumulate in parasite’s food vacuole, disrupt heme polymerization to hemozoin, yielding oxidative damage to membranes and digestive proteases
Thera: Prophylaxis, treatment of acute malarial attacks
Mefloquine (Lariam)
Class: Quinolone derivitive
Mech: Accumulate in parasite’s food vacuole, disrupt heme polymerization to hemozoin, yielding oxidative damage to membranes and digestive proteases
Thera: Prophylaxis, treatment of acute malarial attacks
Primaquine (Primaryl)
Class: Quinolone derivitive
Mech: Forms quinolone-quinone intermediates that oxidize schizont membranes
Thera: Prophylaxis, treatment of acute malarial attacks, also prevent relapses
Important SE’s: Hemolysis (G6PD deficiency), methemoglobinemia
Other SE’s: Fever, nausea, vomiting
Misc: Only drug that inhibits exoerythrocytic schyzogony
Amantadine (Symmetrel)
Mech: Positive charge helps chloroquine overcome chloroquine-resistant malaria vacuoles; point mutations against amantadine return bacteria to chloroquine-sensitivity
Artesunate
Class: Artemisinin compound
Mech: Specifically and selectively inhibit SERCA of P. falciparum
Important SE’s: Neurotoxicity, prolongation of QT interval
Misc: can use IV form for severe cases of malaria
Artemether
Class: Artemisinin compound
Mech: Specifically and selectively inhibit SERCA of P. falciparum
Lumefantrine
Class: Aminoalcohol
Thera: Used in combination w/artemether (called Coartem); want to avoid resistance!!
Misc: Also called benflumentol
Atovaquone (Mepron)
Class: Napthalene
Mech: Depolarizes parasitic mitochondria and inhibits their electron transport
Thera: Used in combination w/proguanil
Misc: use for prophylaxis and treatment of malaria due to P. falciparum, including chloroquine-resistant strains
Chloroguanide (Malarone)
Class: Antifolates
Mech: Dihydrofolate reductase inhibitors (human and parasite pathway)
Important SE’s: Rare
Misc: Also called proguanil
Tetracycline (Tetracyn)
Class: Antibiotic
Thera: Severe malaria & chloroquine-resistant uncomplicated malaria
Clindamycin (Cleocin)
Class: Antibiotic
Thera: Severe malaria & chloroquine-resistant uncomplicated malaria
Doxycycline (Adoxa)
Class: Antibiotic
Thera: Severe malaria & chloroquine-resistant uncomplicated malaria
Important SE’s: Photosensitivity
Characteristics of the five human forms of malaria?
- P vivax: wide distribution, often involved in relapses
- P falciparum: most lethal and common, much resistance to major drugs
- P malariae: less common, could cause asymptomatic infections that can last for decades
- P ovale: less common, involved in relapses
- P knowlesi: thought to be just monkeys, but now some cases in humans
Clinical signs of malaria
- Periodic episodes of chills and fevers
- Usually enlarged liver and spleen
- Identified parasites in blood smears
Frequency of febrile paroxysms:
Vivax: 2 days;
Malariae: 3 days;
Falciparum: irregular
Quinoline derivatives include
quinine/quinidine, chloroquine, mefloquine, primaquine
What is the only parenteral antimalarial available in the US?
Quinine/quinidine (latter with gluconate)
Chloroquine’s uses and where is there sensitivity and resistance?
Prophylaxis and acute attacks;
sens: Central America, Saudi Arabia and Egypt;
resistance: a lot of Africa, Asia, South America
List how chloroquine works on cells with parasites (mechanism):
- Chloroquine can’t leave digestive vacuoles if there is a point mutation preventing chloroquine release
- Chloroquine can be released if there is a mutation in that positive charge
- Give amantadine (an antiviral) that can prevent CQ from exiting again, allowing for toxic complexes of chloroquine and heme to accumulate
- If there’s a mutation such that the channel is resistant to the amantadine, it becomes CQ sensitive again!!
SE’s of mefloquine
Affects nervous system and causes psychotic effects
What does a drug take advantage of to get into a digestive vacuole?
Uses a pH gradient (going from 7.4 to 4.8 from the plasma, RBC cytoplasm, parasite cytoplasm, to food vacuole
Chemoprophylaxis: what do you use in four different areas
CQ-sens zone: chloroquine;
CQ-resistant zone: mefloquine, doxycycline, atovaquone/proguanil;
mefloquine-resistant zone: doxycycline, atovaquone/proguanil;
terminal prophylaxis: primaquine
For treatment of severe malaria, what protocol can you follow?
- IV quinidine gluconate plus tetracycline, doxycycline, or clindamycin (ICU, cardiac function, parasitemia, glucose, Hb, electrolytes)
- IV artesunate followed by atovaquone-proguanil, doxycycline (dlindamycin in pregnant women), or mefloquine
- Exchange blood transfusion (if altered mental status, pulmonary edema, renal complications)
How to treat chloroquine sens strains?
- P falciparum, malariae, or knowlesi by chloroquine phosphate with alternative hydroxychloroquine
- P vivax, ovale: chloroquine phosphate and primaquine phosphate (with alternative hydroxychloroquine and primaquine phosphate)
How to treat CQ-resistant strains?
- P falciparum: atovaquone-proguanil (alternatives artemether-lumefantrine, quinine sulfate plus either doxy, tetra, or clindo for children younger than 8 or preg, and mefloquine)
- P. vivax: quinine sulfate and doxy or tetra, and primaquine phosphate, with alternatives atovaquone-proguanil + primaquine phosphate, or mefloquine and primaquine phosphate
To eradicate persistent exoerythrocytic parasites after clinical cure of acute attack by _____ or _____, what is the drug of choice?
Vivax or ovale; Primaquine phosphate
