Lecture 9 Anti-malarials

Question 1

What species of malaria can form hypnozoites?

Answer 1

P. vivax and ovale

Question 2

What malarial form enters the liver, and what does it develop into there? How long does the liver stage last?

Answer 2

sporozoite–>merozoite; 7 days

Question 3

What plasmodium form enters the RBC and what does it develop into there?

Answer 3

merozoite–>trophozoite

Question 4

What multiples in the RBC, and what does it release when the RBC’s rupture?

Answer 4

trophozoite, merozoite

Question 5

What do female mosquito’s pick up from the blood, and what develops in the mosquito?

Answer 5

gametocytes; sporozoites

Question 6

What drug can kill hypnozoites?

Answer 6

primaquine

Question 7

What drugs can target the liver stage? (4)

Answer 7

artemisinins, primaquine, pyrimethamine, atovaquone (APPA)

Question 8

What drug combination is preferred for chemoprophylaxis of malaria? Why is it preferred?

Answer 8

atovaquone + proguanil (malarone);
short pretreatment (1-2 days) and post treatment (7 days)

Question 9

What other drugs can be used as chemoprophylaxis? What should be used if there is a high amount of p falciparum?

Answer 9

doxycycline, chloroquine, mefloquine;

primaquine

Question 10

For sensitive species, what treatment should be used for malaria?

Answer 10

chloroquine, hydroxychloroquine

Question 11

what should be used for CQ resistant treatment of vivax/ovale?
1. \_\_\_\_ + doxy 
2. \_\_\_\_\_ + \_\_\_\_
3. mefloquine
all should have \_\_\_\_ added!

Answer 11

quinine sulfate
atovaquone, proguanil;;;

all need PRIMAQUINE

Question 12

For severe complicated malaria, what should be used? _____ _____ (with doxy or clindamycin) or artesunate

Answer 12

qunidine gluconate

Question 13

what is a potential severe side effect of quinidine gluconate?

Answer 13

cardiac complications

Question 14

What is the active group of artemisinin? what is the tentative mechanism of action?

Answer 14

endoperoxide; forms free radicals

Question 15

mutations in the ____ gene may cause resistance to artemisinins

Answer 15

kelch 13

Question 16

artemisinin has no effect on _____

Answer 16

hypnozoites

Question 17

one problem with artemisinins

Answer 17

short half life

Question 18

Care should be taken when using HIV drugs such as _____ and _____ in a patient receiving artemisinins due to interactions with CYP3A4

Answer 18

ritonavir;

efavirenz

Question 19

artemisinin is commonly used in combined therapy due to its short half life. what is the most common combo used/its trade name?

Answer 19

lumefantrine + artemisinin; coartem

Question 20

What is the common structure that quinin, mefloquine and chloroquine share?

Answer 20

aminoquinoline

Question 21

aminoquinolines have a ____ structure and are weak ____, allowing them to accumulate in low pH vessels

Answer 21

planar, bases

Question 22

plasmodium ingest Hb from the host cell and degrade it in a _____ _____. the free heme is then polymerized to non toxic ____

Answer 22

food vacuole;

hemozoin

Question 23

chloroquine accumulates in the ____ ___ and inhibits heme _____, causing formation of toxic free radicals

Answer 23

food vacuoule; polymerization

Question 24

mechanism of resistance to 4-substitude quinolines?

due to mutation in ?

Answer 24

lack of accumulation in food vacuole; PfCRT1

Question 25

side effects of chloroquine (3)

Answer 25

pruritus, macular retinopathy, hemolytic anemia if G6PD deficient

Question 26

what interferes with absorption of chloroquine?

Answer 26

kaolin (anti-diarrheal) and antacids

Question 27

Quinine is a ____ schizonticide and is the treatment of choice for CQ resistant _____ malaria (as qunine sulfate) and severe _____ malaria (as quinidine gluconate)

Answer 27

blood; falciprarum; falciparum

Question 28

What is the name of the constellation of symptoms with qunine, and what are they?

Answer 28

Cinchonism–tinnitis, headache, nausea, dizziness, flushing

Question 29

Quinines can also cause ______ _____ if GP6D deficient, as well as ____ fever

Answer 29

hemolytic anemia;

blackwater

Question 30

Mefloquine is effective against _____ forms of P _____ and _____

Answer 30

blood; falciparum, vivax

Question 31

side effects associated with mefloquine?

Answer 31

NEURO-psychiatric toxicity–seizures, toxic psychosis, weird dreams

Question 32

mutations in CYP2D6 can cause issues when using _____

Answer 32

primaquine

Question 33

what is the drug of choice for the liver stage of p vivax and p ovale?

Answer 33

primaquine (+chloroquine)

Question 34

What are 2 contraindications when using primquine?

Answer 34

G6PD deficient–>hemolytic anemia;

pregnancy
also granulocytopenia

Question 35

malarone is a combination of ____ and ____ and is useful in treating the ____ stage

Answer 35

atovaquone, proguanil;

liver and blood!

Question 36

atovaquone is a selective inhibitor of the malarial _____ cytochrome bc1 complex. it is a ____ analog that inhibits _____ transport, causing membrane potential colapse

Answer 36

mitochondrial; ubiquinone; electron

Question 37

proquanil is a selective inhibitor of plasmodial _____ _____ and thymidylate synthase

Answer 37

dihydrofolate reductase

Question 38

pyrimethamine-sulfadoxine (fansidar) are ____ synthesis inhibitors that treat plasmodium and also ____

Answer 38

folate; toxoplasmosis

Question 39

_____ and _____ are antibiotics that act as antimalarials. they are ____ schizonticides

Answer 39

doxy/tetracyline, clindamycin;

blood