Chapter 53 antiprotozoal

Question 1

What is the primary tissue schizonticide that kill schizonts in the liver?

Answer 1

primaquine

Question 2

What are the blood schizonticide kill parasitic forms only in RBC?

Answer 2

chloroquine, quinine

Question 3

What are the sporonticides prevent sporogony and multiplication in mosquito?

Answer 3

Proguanil, pyrimethamine

Question 4

ADME chloroquine

Answer 4

rapidly absorbed orally
large volume of distribution to tissues
excreted largely unchanged in urine

Question 5

What causes decreased oral absorption of the chloroquine?

Answer 5

antacids

Question 6

MOA chloroquine

Answer 6

accumulates in food vacuole of plasmodia, prevents polymerization of Hgb breakdown product into hemozoin => heme is toxic to parasite

Question 7

resistance to cholorquine

Answer 7

P-gp pumps to decrease intracellular accumulation and transporter encoded by pfcrt gene

Question 8

clinical use of chloroquine

Answer 8

DOA for acute attacks of nonfalciparum;
sensitive falciparum malaria;
chemoprophylaxis

=> except in resistant areas

Question 9

What type of drug is chloroquine?

Answer 9

blood schizonticide

Question 10

Other than malaria, what other dz can chloroquine treat?

Answer 10

AI d/o

rheumatoid arthritis

Question 11

At low doses, chloroquine causes what toxicity?

Answer 11

GI irritation;
skin rash;
headaches

Question 12

At high doses, chloroquine causes what toxicity?

Answer 12

severe skin lesions;
peripheral neuropathies & auditory impairment;
myocardial depression, 
retinal damage;
toxic psychosis

Question 13

ADME of quinine

Answer 13

rapidly absorbed orally;
IV admin possible in severe infection (dextrorotary stereoisomer)
metabolized before renal excretion;

Question 14

MOA of quinine

Answer 14

complexes w/ ds DNA to prevent strand separation, resulting in block of DNA replication & transcription to RNA

Question 15

What type of drug is quinine?

Answer 15

solely a blood schizonticide

Question 16

Main use of quinine

Answer 16

P. falciparum infections resistant to chloroquine who can tolerate oral Tx

Question 17

What is quinine commonly used with to treat resistant P. falciparum? why?

Answer 17

Doxycycline or clindamycine to shorten duration of therapy & limit toxicity

Question 18

Why should quinine use be reserved?

Answer 18

to delay resistance

Question 19

Toxicity of quinine

Answer 19

cinchonism => GI distress, headache, vertigo, blurred vision, tinnitus;
severe OD causes cardiac conduction;

Question 20

What type of patient should quinine not be used in?

Answer 20

pregnant;

G6PD deficiency bc hematotoxic hemolysis

Question 21

Describe the rare and sometimes fatal complication in quinine sensitized persons.

Answer 21

Blackwater fever => intravascular hemolysis

Question 22

ADME of mefloquine

Answer 22

due to local irritation => only given orally w/ variable absorption

Question 23

clinical use of mefloquine

Answer 23

1st line Rx (weekly) for prophylaxis in ALL geographic areas w/ chloroquine resistance;
alternative Rx to quinine in acute attacks & uncomplicated P. falciparum

Question 24

Where is resistance to mefloquine located?

Answer 24

SE Asia

Question 25

Toxicity of mefloquine

Answer 25

Common ADE: GI, skin rash, headache, dizzy;

high dose: cardiac conduction defects, psych d/o, neuro Sx, seizures

Question 26

ADME of primaquine

Answer 26

absorption is complete after oral admin;

extensive metab

Question 27

MOA of primaquine

Answer 27

forms quinoline-quinone metabolites that are e- transferring redox compounds that act as cellular oxidants

Question 28

What type of drug is primaquine?

Answer 28

tissue schizonticide;

gametocide (limits malaria transmission)

Question 29

Clinical use of primaquine

Answer 29

eradicates liver stages of P vivax & P ovale & used in conjunction w/ blood schizonticide

Question 30

Give the standard use & concurrent Rx for primaquine’s clinical use

Answer 30

not active alone so has 14day course after Tx w/ chloroquine

Question 31

What is the Rx for daily primary prevention of P. vivax & P. ovale?

Answer 31

primaquine

Question 32

Toxicity of primaquine

Answer 32

well tolerated but some GI, pruritus, headaches, methemoglobinemia;

Question 33

Who should use extreme caution taking primaquine? who should not take it?

Answer 33

G6PD deficiency leads to serious hemolysis;

contraindicated in pregnancy

Question 34

What are the antifolate Rx in Tx of malaria? ADME?

Answer 34

pyrimethamine, sulfadoxine;

orally absorbed;
excreted in urine partially unchanged

Question 35

MOA of sulfonamides

Answer 35

antimetabolites of PABA & block folic acid synthesis in certain protozoans by inhibiting dihydropteroate synthase

Question 36

MOA of Pyrimethamine

Answer 36

selective inhibitors of protozoan dihydrofolate reductases

Question 37

What is the MOA relationship of sulfonamides & pyrimethamine? What Rx do they form when in combo?

Answer 37

combine to form synergistic antimalarial effects through sequential blockade of 2 steps in folic acid synthesis

Question 38

What is the combo Rx of sulfonamides & pyrimethamine? what does it treat?

Answer 38

Fansidar => Tx of chloroquine-resistant forms of P. falciparum but onset of activity is slow

Question 39

Toxicity of sulfonamides

Answer 39

skin rashes, GI, hemolysis, kidney damage,

DDI by competition for plasma protein binding sites

Question 40

Toxicity of pyrimethamine

Answer 40

may cause folic acid deficiency