Anti-malarials

Question 1

which species causes the most mortality and morbidity?

Answer 1

falciparum

Question 2

which species can cause relapse?

Answer 2

vivax and ovale

Question 3

which species only infects OLD senescent RBCs (smoldering subclinical/late presentation infection)

Answer 3

malariae

Question 4

4 classes of antimalarials

Answer 4

quinolones
antifolates/sulfa
antibiotics
artemisinins

Question 5

quinoline and quinoline-like class of antimalarials

Answer 5

disrupts heme polymerization –> parasites due eat Hgb and die from their own waste products

quinine, quinidine, choroquine, hydroxychloroquine, mefloquine, lumefantrine, primaquine

Question 6

which two quinolines are used as prophylais

Answer 6

chloroquine and mefloquine

Question 7

which quinoline can be used as PART or radical cure?

Answer 7

primaquine

Question 8

parenteral quinine/quinidine

Answer 8

used for severe falciparum infections

Question 9

how to treat uncomplicated falciparum?

severe falciparum?

Answer 9

uncomplicated = oral quinine + doxy/clindamycin

severe = parenteral quinine/quinidine

Question 10

side effects of quinine and quinidine

Answer 10

Cinchonism: tinnitus, headache, nausea, bitter taste

arrythmias/prolonged QTc interval/torsades

Induce insulin secretion –>hypoglycemia

Question 11

chloroquine

Answer 11

therapy and chemoprophylaxis

used for a while so now lots of resistance –> can only be used in central america, haiti and dominican rep. for falciparum

usually vivax, ovale, and malariae are sensitive still

Question 12

what drug is falciparum ussually resistant to?

Answer 12

chloroquine

Question 13

mefloquine

Answer 13

long half life - good for bad adherence
use for chloroquine resistant falciparum
also chemoprophylaxis

Question 14

what drug to use for chloroquine resistant falciparum

Answer 14

mefloquine

Question 15

mefloquine side effects

Answer 15

cardiotoxic - dont use with conduction abnormalities

neuropsychiatric side effects/vivid dreams, tics, and motor disorders

Question 16

what drug should be used as prophylaxis for long term travelers and pregnant women?

Answer 16

mefloquine

LONG HALF LIFE

Question 17

PfMDR1

Answer 17

plasmodium falciparum multidrug resistance protein1

efflux pump for mefloquine, quinine, and quinidine

RESISTANCE!!

Question 18

primaquine

Answer 18

used for radical cure and PART (presumptive anti-relapse therapy)

FDA label at 15 mg –> use at 30 mg (higher dose!)

Question 19

PART

Answer 19

presumptive anti-relapse therapy
Prevention of relapses “only for persons who have had prolonged exposure in malaria-endemic areas (e.g., missionaries and Peace Corps volunteers).”

primaquine!

Question 20

primaquine side effect

Answer 20

can trigger hemolysis in G6PD deficiency individuals

test for G6PD before you prescribe primaquine!!

Question 21

test for ____ before you prescribe primaquine!!

Answer 21

G6PD deficiency

due to hemolysis

Question 22

pregnant patients with vivax and ovale infections should be _____

Answer 22

maintained on chloroquine prophylaxis for the duration of their pregnancy

Question 23

anti-folates/sulfa derivatives antimalarial class

Answer 23

Antifolates = Proguanil or Pyrimethamine

Sulfa = Sulfadoxine or Trimethoprim

prototypical drug = sulfadoxine-pyrimethamine

Mechanism: Inhibit Dihydropteroate synthase (DHPS) or dihydrofolate reductase (DHFR) –> nucleic acid synthesis

Question 24

IPT

Answer 24

intermittent preventative treatment
for pregnant women

empiric therapy Used in high malaria transmission regions

Single dose sulfadoxine-pyrimethamine in Africa
Still effective but becoming controversial due to widespread resistance

Question 25

atovaquone - proguanil

Answer 25

Inhibits parasite mitochondrial electron transport USed for both therapy and prophylaxis ``` Causal prophylaxis (blood and liver stage) Well tolerated, take with food/milk to enhance absorption ``` Single point mutation in the parasite cytochrome b gene confers resistance to atovaquone-proguanil If used widespread in endemic setting resistance will rapidly emerge a DAILY med

Question 26

ANTIBIOTIC ANTIMALARIALS

Answer 26

Doxycycline, tetracycline, clindamycin, azithromycin, fluoroquinolones only kills in blood stage Target ribsomal function within the apicoplast organelle Doxy/tetra/clinda used in conjunction with quinine

Question 27

artemisinins

Answer 27

plant derived artemether; arteether; artesunate; dihydroartemisinin broad asexual effects --> blood stages (rings-schizonts), rapid effect mechanism: endoperoxide --> free radicals

Question 28

Artemisinin Combined Therapy (ACT)

Answer 28

2 drugs with different mechanisms for Efficacy and reduce resistance Artemether-lumefantrine 1st line for uncomplicated Pf in most of the world

Question 29

Artemether-lumefantrine

Answer 29

an artemisinin + quinoline | 1st line therapy ACT

Question 30

artesunate

Answer 30

for severe malaria, not FDA approved

Question 31

why are artemisinins more potent?

Answer 31

because of broader activity across the asexual life cycle of malaria more rapid clearance across whole lifecycle

Question 32

presentation of uncomplicated vs severe malaria

Answer 32

Uncomplicated Malaria = Fever, Chills, Headache. Myalgias, Diarrhea, Mild-mod anemia, Mild-mod thrombocytopenia Tolerates oral medications Severe Malaria = Cerebral malaria, confusion, coma, seizure, Hypoglycemia (10%

Question 33

CDC criteria for severe malaria

Answer 33

>5% parasitemia | HgB

Question 34

recommended for uncomplicated faciparum

Answer 34

artemether - lumefantrine atovaquone - proguanil quinine sulfate + doxy or clindamycin

Question 35

recommended for severe falciparum

Answer 35

IV artesunate (1st line) or IV quinine

Question 36

radical cure for relapsing malaria? (vivax or ovale)

Answer 36

choroquine (or any other effective regimen) + primaquine

Question 37

malaria therapy in preganancy

Answer 37

quinine + clindamycin (1st sem) or mefloquine or ACT (2/3rd sem)

Question 38

always ____ patients with falciparum

Answer 38

ADMIT to ensure response to therapy

Question 39

travelers should treaT clothes with...

Answer 39

permethrin

Question 40

neuropsychiatric side effects associated with...

Answer 40

mefloquine | usually not recommended