Malaria Module

Question 1

Chloroquine mechanism

Answer 1

• BInds ferriprotoporyphrin IX and prevents conversion to hemozoin.
• FPIX toxic to plasmodium
• Used to think that it was intercalated between base pairs in DNA inhibiting nucleic acid synthesis

Question 2

Cholorquine basis for selectivity

Answer 2

Selctive accumulation by parasite in erythrocytes. Accumulates in the acid pH of food vacuole. Concentrates at least 25x more in parasitized RBC than unparasitized RBC.

Question 3

Mefloquine, quinine, quinidine mechanism of action and basis for selectivity?

Answer 3

Unknown. Probably acts like chloroquine. Unknown basis for selectivity.

Question 4

Primaquine mechanism and basis for selectivity?

Answer 4

Unknown mechanism. May generation of reactive oxygen species or by interfering with electrion transport in .parasite. Unknown basis for selectivity.

Question 5

Proguanil mechanism

Answer 5

Inhibits folic acid reductase

Question 6

Proguanil basis for selectivity

Answer 6

Species difference in enzyme specificity

Question 7

Atovaquone mechanism

Answer 7

Depolarizes mitochondria and inhibits electron transport

Question 8

Atovaquone basis for selectivity

Answer 8

Species difference in electron transport

Question 9

Artemisinins mechanism

Answer 9

Heme iron in malarial pigment acts on drug to produce free radicals that damage parasite proteins. Inhiits Ca++ ion ATPase in P. falciparum

Question 10

Lumefantrine mechanism

Answer 10

Looks like mefloquine and may act like mefloquine. Unknown.

Question 11

Doxycycline mechanism

Answer 11

Inhibits protein synthesis

Question 12

Chloroquine adverse effects

Answer 12

• Acute attack doses: dizziness, headache, skin rashes, difficulty in visual accomodation.
• Large doses for prolonged periods can cause severe eye damage and even blindness

Question 13

Quinine and Quinidine use

Answer 13

Used in chloroquine resistant p. falciparum

Question 14

Quinine and Quinidine adverse effects

Answer 14

-Acute attack doses: Cinchonism (tinnitus, blurred vision, nausea, headache, decreased hearing acuity). Permanenet damage to balance, hearing, and vision can occur.

Question 15

Specific quinidine problems

Answer 15

Can cause cardiac issues (drug also used to maintain sinus rhythm in A. fib.
-Given IV for severe malaria

Question 16

Mefloquine indications

Answer 16

ONLY for treatment and prevention of Chloroqine resistant p. falciparum

Question 17

Mefloquine adverse effects

Answer 17

• May cause disorientation, hallucinations, depression

- Nausea, vomiting, dizziness, visual or auditory disturbances.

Question 18

Atovaquone and proguanil

Answer 18

• Slow onset
• Unclear effectiveness against exoerythrocytic forms
• Expensive and needs to be taken daily
• Replacing mefloquine for prophylaxis
• GI disturbances can occur

Question 19

Artemisinins and combos. Why in combination?

Answer 19

To try and prevent resistance to these drugs from occurring

Question 20

Lumefantrine

Answer 20

• Effective against erythrocytic stage

- More slowly eliminated

Question 21

Primaquine drug of choice for what?

Answer 21

Eliminaton of hepatic forms of P. vivax and P. ovale–> eradicates the hypnozoite forms dormant in the liver.

Question 22

Primaquine adverse effects

Answer 22

Occasional GI distress, nausea, headache, pruitis, leukompenia. Hemolytic anemia in people with G6PD deficiency.

Question 23

In what 2 species of plasmodium does drug resistance readily occur?

Answer 23

P. vivax and p. falciparum