Exam 4

Question 1

Which malaria strains have a hipnozoite stage?

Answer 1

P. vivax; P. ovale. Allows dormancy and relapse months-years later.

Question 2

Artemether- Indication

Answer 2

Active against blood-stage infections (gametocyte and asexual). Newest agent, ALWAYS given in combination. IV artesunate preps are given in severe/complicated P. falciparum malaria (available from CDC only).

Question 3

Lumefantrine

Answer 3

In the USA, this is the first line. It is given in combination with artemether as ACT.

Question 4

First line against P. falciparum

Answer 4

ACT- artemether+lumefantrine

Question 5

Quinine sulfate- indication

Answer 5

oldest anti-malarial. Used for P.vivax with chloroquine resistance (or acquired in Papua New Guinea/Indonesia). IV quinidine can be used in complicated malaria with tetra, doxy, or clindamycin.

Question 6

Chloroquine phosphate- indication

Answer 6

Used to treat P. vivax, P. ovale, P. malariae, P. knowlesi acquired in non-resistant areas. Also effective as prophylaxis in these areas.

Question 7

Primaquine- indication

Answer 7

Effective against primary and hypnozoite liver stages of P. vivax and P. ovale- so useful to prevent relapse infection. Not very effective against gametocytes.

Question 8

Doxycycline- indication for malaria.

Answer 8

Can be given as adjunctive with a quinoline (usually quinine), or alone as prophylaxis.

Question 9

Clindamycin- indication for malaria

Answer 9

Adjunctive with quinolines only as second line. (w/quinine sulfate)

Question 10

Atovaquone-Proguanil- indication

Answer 10

Active against primary liver stage (not hypnozoite), but is useful against gametocyte blood stage. Also used for prophylaxis (Malarone).

Question 11

Artemisinins: mechanism

Answer 11

Not super-clear. Effective against blood stages of P. falciparum and P. vivax. Activity is attributed to endoperoxide moiety which creates toxic adducts with heme and protein. Mechanism of emerging resistance is not clear

Question 12

Why aren’t artemisinins useful for prophylaxis?

Answer 12

Short half-life (1-2 hrs)

Question 13

ACT- adverse events

Answer 13

Substantial drug interactions with ARVs (esp PIs) may require increased dose of ACT. Otherwise, well tolerated. Not recommended for women in 1st trimester of pregnancy, children <5kg.

Question 14

Quinolines: mechanism

Answer 14

Interferes with Heme digestion.

Question 15

In general, when are quinolines indicated

Answer 15

Mainstay of treatment for chloroquine-R and MDR P. falciparum asexual blood stages; gametocyticidal against P. vivax and P. ovale. IV quinidine is more potent and often used in severe malaria. It is also safe for pregnant women and clears infection from fetus.

Question 16

Quinolines: resistance mechanism

Answer 16

Pfmdr1 gene amplification has been found in SE asia and SA. It’s a multidrug transporter.

Question 17

Quinine: adverse events

Answer 17

Fatal oral dose is 2-8 grams. Cinchonism (tinnitus, deafness, visual disturbance, headache, nausea, vomiting, dizziness, flushing).
**Causes hemolysis in G6PD deficiency.

Question 18

Quinine: CI and drug interactions:

Answer 18

CI: in patients with tinnitus/optic neuritis
Caution in pts with hypersensitivity and discontinue if evidence of hemolysis. Use caution in pts with dysrhythmias.

Aluminum containing antacids delay GI absorption. Increases warfarin and digoxin levels. Reduce dose with renal insufficiency.

Question 19

Adjunctive malaria thereapy (doxycycline, clindamycin) mechanism:

Answer 19

Inhibit protein translation in protozoa.

Question 20

Chloroquine: resistance mechanism

Answer 20

pfcrt mutations (pumps protonated chloroquine out)

Question 21

Chloroquine: adverse events

Answer 21

Note: narrow safety margin with complex kinetics (especially in parenteral route where doses>5g are fatal). Causes acute toxicities to CV and CNS.
*Hemolysis in G6P deficiency.
Pruritis in people of African descent.

Question 22

Primaquine: Adverse events

Answer 22

Risk of hemolysis in persons with G6PD deficiency is higher than in other quinolines!! ALWAYS screen for g6pd deficiency.

Other adverse events are related to the potential for conversion into electrophilic intermediates that mediate redox rxns (also interferes with mitochondrial ETC in parasite).

Give orally. Parenteral route increases risk of hypotension.

CI in pregnant women!!
R/O G6PD deficiency in breastfeeding infants first.

Question 23

Atovaquone mechanism and resistance mechanism.

Answer 23

Effective against liver stages where it inhibits parasite mitochondrial electron transport chain.
Resistance is by Cyt bmutations that inhibit drug binding.
Always combine with proguanil.

Question 24

Atovaquone: Drug interactions

Answer 24

Rifampin, tetracycline bother reduce plasma levels of atovaquone.

Question 25

Proguanil: mechanism

Answer 25

Inhibits dihydrofolate (DHF) reductase, enhancing effect of atovaquone.