Malaria Treatment - Regal

Question 1

Suppressive Prophylactic Treatment

Answer 1

Malaria: Chloroquine
2nd: Atovaquone/proguanil
Chloroquine-Resistant Malaria: Atovaquone/proguanil
2nd: Doxycycline or Mefloquine

Question 2

Clinical status of Severe Malaria Disease

Answer 2

Most deaths from severe malaria occur within the first 24-48 hours, so we need a parenteral therapy that acts quickly

Question 3

Why is Primaquine considered the “radical cure”?

Answer 3

It acts on the latent hepatozoite Exoerythrocytic forms of P. vivax and P. ovale

Question 4

What type of plasmodium have the most resistance to treatment?

Answer 4

P. vivax

P. falciparum

Question 5

What type of plasmodium have a persistent hepatic form?

Answer 5

P. vivax

P. ovale

Question 6

Atovaquone/Proguanil

Answer 6

Atovaquone
MoA: depolarizes parasitic mitochondria and inhibits their electron transport
Selectivity: plasmodial electron transport
Toxicity: drug interactions

Proguanil (metabolite of atovaquone)
MoA: inhibits DHFR
Selectivity: plasmodial enzyme DHFR; slow onset
Toxicity: GI disturbances

Question 7

Chloroquine

Answer 7

MoA: Disrupts sequestration of heme as hemozoin; keeps heme in toxic form
Selectivity: parasitized RBC concentrates Chloroquine 25x more than unparasitized RBC and accumulated in the acidic pH of food vacuole
Toxicity: visual accommodation, large doses = blindness

Question 8

Doxycycline

Answer 8

MoA: Inhibits protein synthesis by binding to the 30S ribosomal subunit
Selectivity:
Toxicity: Photosensitivity Rash

Question 9

Mefloquine

Answer 9

MoA: unknown; may disrupt sequestration of heme as hemozoin
Selectivity: Unknown
Toxicity: Neuropsychiatric reactions, N/V

Question 10

Primaquine

Answer 10

MoA: unknown; reactive oxygen species or interfering with electron transport in the parasite
Selectivity: unknown; eradicates hypnozoite forms dormant in liver
Toxicity: N/V, leukopenia, hemolytic anemia w/ G6PD

Question 11

Quinine

Answer 11

MoA: unknown; may disrupt sequestration of heme as hemozoin
Selectivity: unknown; used in chloroquine resistant P. falciparum
Toxicity: More toxic than chloroquine; tinnitus, blurred vision, headache, nausea, damage to vision, balance and hearing

Question 12

Quinidine

Answer 12

MoA: unknown; may disrupt sequestration of heme as hemozoin; blocks Na and K currents (a fib treatment)
Selectivity: unknown; used in chloroquine resistant P. falciparum; given IV
Toxicity: Cardiac problems

Question 13

Artemisinins and combinations (ACT = artemisinin-based combination therapy)

Answer 13

MoA: Heme iron acts on drug to produce free radical to damage parasite proteins; inhibits Ca2+ ATPase in P. falciparum
Don’t use Artemisinins alone to avoid forming resistance.

Question 14

Artemether/Lumefantrine

Answer 14

MoA: Unknown

Longer half-life and effective against erythrocytic stage