Anti-Malarials

Question 1

Ancient Chinese herbal remedy (sweet wormwood)

Answer 1

Artemisinins

Question 2

Paired together because one has a short half life and one has a long half life. Both are blood schizontizides.

Answer 2

ACT with Lumefantrine (Coartem) Artemether+Lumefantrine.

Question 3

Mainstay for chloroquine-R and MDR P. falciparum asexual blood stages; gametocyticidal against P.vivax and P.ovale

Answer 3

Quinine Sulfate

Question 4

Highly effective against P. vivax, P.ovale, P. malaria and P. knowlesi and Chloroquine-S P. falciparum asexual blood stages, with some gametocytocidal activity.

Answer 4

Chloroquine Phosphate

Question 5

Acts on primary and latent hepatic stages of plasmodia; effective against P. vivax and P. ovale.

Answer 5

Primaquine

Question 6

Antibiotic that can be used in conjunction with anti-malarials.

Answer 6

Doxycycline

Question 7

Antibiotic used in conjunction with anti-malarials to treat other protozoal infections like babesiosis, amebiasis and pneumocystitis jiroveci.

Answer 7

Clindamycin

Question 8

Active against P. falciparum asexual blood stages and liver stages.

Answer 8

Atovaquone-Proguanil

Question 9

Do anti-malarials work singly or do they have to be used in combination?

Answer 9

No single anti-malarial is effective against all liver and blood stages of the plasmodium life-cycle so you have to use a combination of drugs.

Question 10

Active against P. falciparum and asexual blood stages of P. vivax as a gametocytocidal.

Answer 10

Artemisinins

Question 11

Anti-malarial activity due to endoperoxide moiety

Answer 11

Artemisinins

Question 12

Not useful for prophylaxis because of a short t 1/2 life. Results in increased failure as a monotherapy

Answer 12

Artemisinins

Question 13

Artemisinin-based Combination Therapy (ACT) results in…

Answer 13

Increased efficacy and decreased resistance

Question 14

Artemisinin’s MOA

Answer 14

Toxic adducts- Peroxide “bridge” potentially reduced by heme.

Question 15

Substantial drug-drug interactions with anti-retrovirals/protease inhibitors (need to increase the anti-malarial dose)

Answer 15

ACT- Artemether-lumefantrine

Question 16

Artemisin Adverse Effects

Answer 16

Generally well tolerated

Not recommended in 1st trimester of pregnancy or in children under 5kg.

Question 17

Interferes with heme digestion

Answer 17

Quinine Sulfate

Question 18

Resistance reported in SE Asia, South America from the Pfmdr1 gene amplification

Answer 18

Quinine Sulfate

Question 19

Quinine Adverse Effects

Answer 19

Fatal oral dose (adults) 2-8 grams
Cinchonism: tinnitus, deafness, visual disturbance, headache, nausea, vomiting, dizziness, flushing.
Hematologic abnormalities: hemolysis with G6PDH deficiency.

Question 20

Quinine C/I

Answer 20

Caution in pts. with hypersensitivity
C/I in pts. with tinnitus/optic neuritis
Caution in pts. with cardiac dysrhythmias

Question 21

Quinine DDI’s

Answer 21

Aluminum containing antacids delay GI absorption
Increased plasma warfarin and digoxin levels
Decrease dose in pts. with renal insufficiency

Question 22

Interferes with Heme Digestion best to take Orally b/c parenteral routes can result in potentially lethal Cp

Answer 22

Chloroquine

Question 23

Chloroquine MOA

Answer 23

Binds hemazoin in parasitized erythrocytes, causing cell lysis. pfcrt mutations associated with resistance (drug efflux also with CRT)

Question 24

Chloroquine Adverse Effects

Answer 24

Narrow safety margin
Acute toxicities in CV and CNS
IV doses >5g usually fatal
hemolysis with G6PDH deficiency
Pruritis in persons of African descent

Question 25

Hemolysis in G6PDH deficiency, screen before giving drug.
Don’t give IV b/c of risk of HoTN
C/I in pregnant women, screen babies for G6PDH deficiency before giving to a breast feeding mom.

Answer 25

Primaquine

Question 26

Inhibits parasite mitochondrial ETC- inhibits CoQ turning on cytochrome b.
High cure rates when combined with proguanil.
Proguanil inhibits dihyrdofolate reductase. Synergistic with atovaquone.

Answer 26

Atovaquone-proguanil

Question 27

Used for chemoprophylaxis/uncomplicated P. falciparum

Answer 27

Atovaquone-proguanil