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