Antimalarials

Question 1

which form of malaria have two types of stages/parasite forms to eliminate and why

Answer 1

• plasmodium vivax and ovale both have a dormant hepatic stage so both erythrocytic and hepatic parasites must be eliminated
• plasmodium falciparum and malariae only have erythrocytic parasites to eliminate

Question 2

which form of malaria can have an incubation period that can last years

Answer 2

plasmodium malariae

Question 3

symptoms of malaria

Answer 3

malaria paroxysm (sudden attack) - fever, anemia, splenomegaly, jaundice, hepatomegaly

Question 4

which form of malaria is most severe and why

Answer 4

plasmodium falciparum –> cerebral malaria

• irritability, seizure, coma
• also respiratory distress syndrome, diarrhea, severe thrombocytopenia, spontaneous abortion, hypoglycemia

Question 5

treatment of malaria should be guided by what

Answer 5

• species of infecting plasmodium
• clinical status of patients
• drug susceptibility of infecting parasites

Question 6

major antimalarial drugs

Answer 6

CAM PADS Q

Chloroquine
Quinine and Quinidine
Mefloquine
Primaquine
Atovaquone
Sulfadoxine-Pyrimethamine
Doxycycline
Artemisinins

Question 7

clinical application of chloroquine

Answer 7

treatment and prophylaxis of plasmodium vivax and ovale

sensitive uncomplicated falciparum

Question 8

MOA of chloroquine

Answer 8

prevents biocrystallization of hemoglobin breakdown product heme to non toxic hemozoin –> accumulation of heme –> lysis of parasite and RBC –> effective against blood parasites and not liver parasites

Question 9

what is resistance against chloroquine

Answer 9

plasmodium falciparum – due to mutations in putative transporter, PfCRT

Question 10

adverse effects of chloroquine

Answer 10

Pruritus (most common)

Hemolysis in G6PD deficiency

Question 11

contraindications of chloroquine

Answer 11

patients with psoriasis or porphyria (precipitate attacks)

retinal or visual field abnormalities

Question 12

what are quinine and quinidine used for

Answer 12

severe forms of plasmodium falciparum malaria

quinine is oral and quinidine is parenteral

Question 13

mechanism of quinine and quinidine

Answer 13

depresses O2 uptake and carb metabolism –> intercalates into DNA –> disrupts parasites replication and transcription –> only good for blood parasites

Question 14

adverse effects of quinine and quinidine

Answer 14

CHHHUBES

Cinchonism - tinnitus, visual probs, dizziness
Hypersensitivity - skin rash, urticaria
Hematological abnormalities
Hypoglycemia - stimulates insulin release
Uterine contractions
Blackwater fever - hemolysis and hemoglobinuria
ECG abnormalities - QT prolongation
Severe hypotension - too rapid IV infusion

Question 15

contraindications of quinine and quinidine

Answer 15

• visual or auditory problem (cinchonism)
• cardiac abnormalities (ECG problems)
• raises levels of warfarin and digoxin
• reduced dose in renal insufficiency
• don’t use with mefloquine

Question 16

MOA of Mefloquine and its clinical application

Answer 16

destruction of asexual blood forms of malarial pathogens

chemoprophylaxis in preggos in chloroquine resistant areas

Question 17

what drug does mefloquine causes a resistant to

Answer 17

quinine

Question 18

adverse effects of Mefloquine

Answer 18

Neurologic and psychiatric toxicities

Cardiac conduction defects

Question 19

contraindications of Mefloquine

Answer 19

• Do not administer with quinine, quinidine, and halofantrine
• Patients with history of neurologic, psychiatric, and cardiac problems

Question 20

drug of choice for dormant liver form of plasmodium vivax and ovale

Answer 20

primaquine

Question 21

adverse effects of primaquine

Answer 21

Hemolysis
Methemoglobinemia
both especially in G6PD deficiency since primaquine further decreases available GSH by oxidizing it to GSSG

Question 22

contraindication of primaquine

Answer 22

G6PD deficiency

Pregnancy - fetus is relatively G6PD deficient

Question 23

what is Malarone

Answer 23

Atovaquone + Proguanil

Question 24

MOA of malarone and clinical application (what is it again)

Answer 24

atovaquone + proguanil

disrupts mitochondrial electron transport –> used for plasmodium falciparum

Question 25

contraindications of Malarone (name what it is)

Answer 25

Atovaquone + Proguanil Pregnancy

Question 26

inhibitors of folate synthesis used as antimalarials

Answer 26

Pyrimethamine Proguanil Sulfadoxine

Question 27

MOA of the antimalarial inhibitor of folate synthesis

Answer 27

Pyrimethamine + Proguanil = inhibitor plasmodial dihydrofolate reductase Sulfadoxine = inhibit dihydropteroate synthase

Question 28

of the three antimalarial inhibitor of folate synthesis, which works weakly on hepatic forms

Answer 28

Proguanil

Question 29

adverse effects of antimalarial inhibitor of folate synthesis (individually)

Answer 29

Pyrimathamine-Sulfadoxine: Erythema Multiforme, Stevens-Johnson, Toxic epidermal necrolysis Proguanil: mouth ulcers, alopecia Sulfadoxine: Hematological, GI, CNS, dermatologic, and renal toxicities

Question 30

clinical application of doxycycline

Answer 30

prophylaxis for all form treatment of p. falciparum not used against liver stages

Question 31

adverse effects of doxycycline and contraindications

Answer 31

- stunting of growth - discoloration and hypoplasia of teeth - fatal hepatoxicity in pregnancy -don't use in pregnancy and children under 8

Question 32

types of artemisinins

Answer 32

artesunate artemether dihydroartemisinin coartem

Question 33

MOA of artemisinins

Answer 33

binds to iron --> breaks down peroxide bridges --> free radical generation -> damage parasitic protein

Question 34

other antimalarials

Answer 34

Clindamycin Halofantrine Lumefantrine

Question 35

adverse effects of halofantrine

Answer 35

teratogenic

Question 36

when is mefloquine usually given

Answer 36

when chloroquine resistant especially in preggos

Question 37

what is given as prophylaxis when chloroquine resistant

Answer 37

mefloquine, doxycycline, primaquine