Pharm - Antiprotozoal Drugs Part 2

Question 1

primaquine is used to eradicate ____ forms of ___ and ____

Answer 1

DORMANT forms of VIVAX and OVALE

Question 2

explain the MOA of primaquine

it is active against ___ ___ forms

Answer 2

primaquine produces an electrophile that creates oxidative stress to kill the parasite

active against LATENT HEPATIC forms

Question 3

true or false

primaquine is only active against hepatic forms

Answer 3

TRUE

Question 4

primaquine is used in combination with _____to prevent _____

Answer 4

chloroquine (erythrocytic forms)
to prevent RELAPSE

Question 5

some AE of primaquine

Answer 5

methemoglobinemia in G6PDH deficiency, hemolysis

leukpenia, cardiac arrythmia, etc

Question 6

atavoquone MOA

Answer 6

disrupts the mitochondrial electron transport chain of the parasite – can’t generate ATP

Question 7

atovaquone is active against ___ and ___ schizonts

Answer 7

blood and tissue

Question 8

resistance mechanism for atovaquone and what can reduce the ressitance

Answer 8

SNP in the mitochondrial cytochrome b gene

administering atovaquone with proguanil decreases resistance

Question 9

MOA of pyrimethamine and proguanil

Answer 9

selectively inhibits plasmodial DHFR – thus inhibiting folate biosynthesis and the synthesis of thymine – 1/4 of the building blocks of DNA

Question 10

what are pyrimethamine and proguanil administered with and why

Answer 10

sulfa drugs!
they block DHPS (dihydropteroate synthase)

Question 11

___ (how many) main mechanisms of resistance drive plasmodium resistance to antimalarial drugs:

give example of each

Answer 11

1. efflux of the drug away from its site of action (ie - pfcrt in chloroquine resistance)
2. change in the target due to mutations in the corresponding genes (ie - DHFR and DHPS mutation in sulfadoxine-pyrimethamine resistance)

Question 12

in which targeted stage of the malarial life cycle are there more mutations/resistance and why?

Answer 12

the blood/erythrocytic stage

parasite is getting a lot more nutrients

Question 13

chemically, what are metronidazole/tinidazole

Answer 13

nitroimidazoles

Question 14

MOA of nitroimidazoles like metronidazole and tinidazole

Answer 14

inhibits nucleic acid synthesis by disrupting DNA and causing strand breakage

Question 15

nitroimidazoles are the drug of choice for ___ ___

Answer 15

extraluminal amebiasis

Question 16

common/rare AEs of nitroimidazoles

any BBW

Answer 16

common - nausea, dry mouth, metallic taste

rare - pancreatitis CNS toxicity

BBW = possible carcinogenic effect (shown possible in animals)

Question 17

can metronidazole be used in pregnant women

Answer 17

NO

Question 18

iodoquinol is halogenated _________

Answer 18

hydroxyquinolone

Question 19

MOA of iodoquinol

Answer 19

interferes with heme metabolism of protozoa

Question 20

cautions w iodoquinol

Answer 20

neuropathy, discontinue if any signs of iodine toxicitiy

Question 21

in general what is paromomycin sulfate and what is it used for

Answer 21

an aminoglycoside antibiotic

used as a luminal amebicide

Question 22

toxicity of paromomycin

Answer 22

causes renal toxicity in pts with renal insufficiency (aminoglycoside antibiotic!)

Question 23

*Artemisinin-based combination therapies are recommended by the WHO for treating WHICH TYPE OF MALARIA

Answer 23

plasmodium falciparum malaria

Question 24

which of the following antimalarial drugs are SAFE in pregnancy

quinine
chloroquine
atovaquone-proguanil
artemether-lumefantrine

Answer 24

all are safe except artemether - lumefantrine

Question 25

what drug is effective against the LIVER STAGE of plasmodium vivax and plasmodium ovale

Answer 25

primaquine

Question 26

hypnozoites

Answer 26

liver stage

Question 27

MOA of chloroquine in treating malaria

Answer 27

interferes with hemoglobin metabolism in the parasite (Hz - non toxic form - cannot be produced)

Question 28

what antimalarial drug is known for causing vivid dreams and other neuropsych side effects

Answer 28

mefloquine