AntiMalarials

Question 1

Levels of AntiMalarials

Answer 1

1 - Blood stages only (falciparum)
2 - Blood and liver (falciparum and some vivax)
3 - Liver stages of vivax and ovale and gametocyte blood stage

Question 2

Level 1 Antimalarials

Answer 2

Artemisinins: Artemether and ACT
Quinolones: Quinine Sulfate, Quinidine Gluconate, Chlorquine Phosphate

Question 3

Level 2 AntiMalarials

Answer 3

Atovaquone

Proguanil

Question 4

Level 3 AntiMalarials

Answer 4

Primaquine

Question 5

AntiMalarial General Mechanisms of Action

Answer 5

Inhibit Electron Transport Chain
Oxidative Stress in Cytosol
Interference with DNA/RNA Synthesis
Inhibition of Heme Degradation

Question 6

Artemisinins

Answer 6

“Not very good at it’s ART, so it usually is given in combination therapy.” (Increases effective time and decreases resistance development)
Asexual blood stages
Endoperoxide moiety that clings to heme and prevents polymerization. BUILDUP of PROTOZOA POOP!
Short t1/2

Question 7

Artemether-Lumefantrine

Answer 7

Called Coartem
Typically IV
Lumefantrine has longer t1/2
Interactions with Protease Inhibitors and ARVs 
Preg CatC

Question 8

Quinolones

Answer 8

• Falciparum asexual blood stages, gametocyticidal against vivax and ovale
• Interferes with Heme Digestion so Protozoa STARVE
• Quinidine is a more potent and toxic enantiomer
• Oral, aluminum antacids delay absorption
• EXTENSiIVE metabolism by liver (increases warfarin and digoxin levels)
• Kidney excre.
• Dose-concentration can be FATAL, Hematologic abnormalities, and CINCHONISM
• Pregnancy C because gets to fetus
• Resistance development due to mutation in transporter that kicks drug out, Pfmdr1.

Question 9

Quinolone Adjunctive Therapies

Answer 9

Tetracyclines (doxy and tetra) and Clindamycin used to inhibit protein translation to boost Quinolone effect.

Question 10

Chloroquine Phosphate

Answer 10

Level 1 Antimalarial: vivax, ovale, and sensitive falciparum in blood
Interferes with Heme Polymerization. PROTOZOA POOP.
ORAL (IM, SC, IV)
Complex excre. because goes to tissues differently
IV can be lethal (>5g): LOW AND SLOW. Acute CV and CNS toxicities due to IV
Pruritis in dark-skinned.
Caution in patients with advanced liver/kidney disease or severe GI or neuro or blood DO.
Resistance with Pfcrt, transporter out of digestive vacuole

Question 11

Primaquine

Answer 11

“It is of PRIME importance to check G6PD levels for patients taking Primaquine.”
Level 3 Antimalarial - Liver stages vivax and ovale
Uses up Glutathione (GSH) in cytosol, so buildup of free radicals causes oxidative stress.
CONTRAINDICATED in G6PD deficiency, major HEMOLYSIS, also pregnancy and lactation unless baby is ok.

Question 12

Quinine Sulfate

Answer 12

Level 1 AM: falciparum and vivax
Oral, Aluminum antacids interfere with absorption
Kidney excre. faster when urine is acidic
Minor CNS
More toxic, less effective than chloroquines: Contraindicated in Pts with problems similar to toxicities, blood issues, neuro issues.

Question 13

Quinidine Gluconate

Answer 13

Level 1 AM: SEVERE all species
IV
Conchonism and CV issues (tachy, flat t-wave, ventricular arrythmias, etc.)
Combo with tetra~ doxy~ or Clindamycin.
More toxic, less effective than chloroquines: Contraindicated in Pts with problems similar to toxicities, blood issues, neuro issues.

Question 14

Level 2 AntiMalarials

Answer 14

Atovaquone and Proguanil

Question 15

Atovaquone-Proguanil

Answer 15

falciparum (blood and LIVER stages) from chloroquine resistant areas, vivax (not liver)
Ato:Changes activity of CytB in mitochondria to interrupt ETC!
Proguanil: Inhibits Folic Acid Synthesis via dihydrofolate reductase. So, also can act against other protozoa.
Oral, best with food
Mild GI, reversible liver enzyme elevations
Contraindicated: pregnancy, hypersensitivity
Minor metabolism by liver means that there are REDUCED SERUM LEVELS with Rifampin or Tetracylcine that inhibit p450.
Mutations to CytB will decrease drug activity