Block 10 Antiprotozoal Drugs

1. A 45-year-old black man referred to his physician that few days ago he noticed a persistent yellow color in his eyes . One week before, coming back from a trip to central America, the man had started a treatment which included primaquine. A blood test disclosed the following: RBC count: 3.8 x 106/ mm3 (normal: 4-5.5) Hb: 9 g/dL (normal: > 12) Reticulocytes: 3.7% of red cells (normal 0.5-1.5%) WBC count 12000/mm3 (normal: 3200-9800) The physician told the patient that he probably had a genetically induced enzyme defect. Which of the following enzymes was most likely abnormal?

Thymidylate synthase

Uroporphyrinogen decarboxylase

Pyruvate kinase

Dihydrofolate reductase

Glucose-6-phosphate-dehydrogenase

The patient's symptoms of persistent yellow color in his eyes and abnormal blood test results, specifically low RBC count, low Hb, and high reticulocytes, suggest that he is experiencing hemolysis, which is the breakdown of red blood cells. The most likely cause of hemolysis in this case is a deficiency in the enzyme glucose-6-phosphate-dehydrogenase (G6PD), which is responsible for protecting red blood cells against oxidative damage. Primaquine, the medication the patient started taking, is known to cause hemolysis in individuals with G6PD deficiency. Therefore, G6PD is the most likely enzyme that is abnormal in this patient.

Explanation

The patient's symptoms of persistent yellow color in his eyes and abnormal blood test results, specifically low RBC count, low Hb, and high reticulocytes, suggest that he is experiencing hemolysis, which is the breakdown of red blood cells. The most likely cause of hemolysis in this case is a deficiency in the enzyme glucose-6-phosphate-dehydrogenase (G6PD), which is responsible for protecting red blood cells against oxidative damage. Primaquine, the medication the patient started taking, is known to cause hemolysis in individuals with G6PD deficiency. Therefore, G6PD is the most likely enzyme that is abnormal in this patient.

2. A 45-year-old reporter who was about to leave for Honduras, started a prophylactics antimalarial treatment with chloroquine. Which of the following molecular actions most likely mediate the therapeutic effect of this drug?

Inhibition of dihydropteroate synthase

Blockade of translocation of peptidyl-tRNA

Incorrect amino acid incorporation into the polypeptide chain

Inhibition of DNA-dependent RNA polymerase

Prevention of polymerization of free heme into hemozoin

Chloroquine is an antimalarial drug that works by preventing the polymerization of free heme into hemozoin. Malaria parasites digest hemoglobin and release free heme, which is toxic to the parasite. However, the parasite converts this free heme into hemozoin, a non-toxic substance. Chloroquine inhibits this process, leading to the accumulation of toxic free heme and ultimately killing the parasite. This is the molecular action that mediates the therapeutic effect of chloroquine in treating malaria.

Explanation

Chloroquine is an antimalarial drug that works by preventing the polymerization of free heme into hemozoin. Malaria parasites digest hemoglobin and release free heme, which is toxic to the parasite. However, the parasite converts this free heme into hemozoin, a non-toxic substance. Chloroquine inhibits this process, leading to the accumulation of toxic free heme and ultimately killing the parasite. This is the molecular action that mediates the therapeutic effect of chloroquine in treating malaria.

3. A 35-year-old woman was planning a trip to malaria endemic regions of central America. She was advised by her physician to take a tablet of pyrimethamine-sulfadoxine (fansidar) in case of fever and then to obtain as soon as possible medical attention. The antimalarial efficacy of pyrimethamine is most likely mediated by the inhibition of which of the following protozoal enzymes?

Purine phosphoribosyl transferase

Ornithine decarboxylase

Ferredoxin oxidoreductase

Dihydropteroate synthetase

Dihydrofolate reductase

Pyrimethamine is a medication commonly used for the treatment and prevention of malaria. Its antimalarial efficacy is primarily due to its inhibition of the enzyme dihydrofolate reductase (DHFR) in the malaria parasite. DHFR is involved in the synthesis of tetrahydrofolate, which is essential for the production of DNA and RNA in the parasite. By inhibiting DHFR, pyrimethamine disrupts the synthesis of these nucleic acids, leading to the death of the parasite. Therefore, the correct answer is dihydrofolate reductase.

Explanation

Pyrimethamine is a medication commonly used for the treatment and prevention of malaria. Its antimalarial efficacy is primarily due to its inhibition of the enzyme dihydrofolate reductase (DHFR) in the malaria parasite. DHFR is involved in the synthesis of tetrahydrofolate, which is essential for the production of DNA and RNA in the parasite. By inhibiting DHFR, pyrimethamine disrupts the synthesis of these nucleic acids, leading to the death of the parasite. Therefore, the correct answer is dihydrofolate reductase.

4. A 31-year-old man, coming back from a trip to Malaysia, was admitted to the hospital with a two day history of fever, chills and bouts of diarrhea. A Giemsa blood smear demonstrated P. Vivax trophozoites. The patient was placed on chloroquine for 5 days, then he was instructed to take another drug for 14 days. Which of the following drugs was most likely prescribed?

Primaquine

Mefloquine

Quinidine

Pyrimethamine

Doxycycline

Sulfadoxine

The patient is diagnosed with P. Vivax malaria, as indicated by the presence of P. Vivax trophozoites in the blood smear. Chloroquine is the first-line treatment for P. Vivax malaria, which the patient was prescribed for 5 days. However, chloroquine does not eliminate the dormant liver stage of the parasite, which can cause relapses. Primaquine is the drug of choice for eradicating the liver stage of P. Vivax and preventing relapses. Therefore, the most likely drug prescribed for the patient after chloroquine treatment is Primaquine.

Explanation

The patient is diagnosed with P. Vivax malaria, as indicated by the presence of P. Vivax trophozoites in the blood smear. Chloroquine is the first-line treatment for P. Vivax malaria, which the patient was prescribed for 5 days. However, chloroquine does not eliminate the dormant liver stage of the parasite, which can cause relapses. Primaquine is the drug of choice for eradicating the liver stage of P. Vivax and preventing relapses. Therefore, the most likely drug prescribed for the patient after chloroquine treatment is Primaquine.

5. A 34-year-old black man permanent US is planning to visit his seriously ill father who lives in Uganda. He will be accompanied by his wife and son. Knowing that chloroquine-resistant strains of malaria are present in Uganda, which of the following drugs used alone should be administered to the man, his wife and son before entering Uganda?

Primaquine

Metronidazole

Pyrimethamine

Mefloquine

Chloroquine

Quinine

Mefloquine is the correct answer because it is effective against chloroquine-resistant strains of malaria, which are present in Uganda. The man, his wife, and his son should be administered Mefloquine before entering Uganda to protect themselves from contracting malaria. Primaquine is not recommended for prevention, Metronidazole is used for bacterial and parasitic infections but not malaria, Pyrimethamine is used in combination with sulfadoxine for treatment but not prevention, Chloroquine is not effective against chloroquine-resistant strains, and Quinine is used for treatment but not prevention of malaria.

Explanation

Mefloquine is the correct answer because it is effective against chloroquine-resistant strains of malaria, which are present in Uganda. The man, his wife, and his son should be administered Mefloquine before entering Uganda to protect themselves from contracting malaria. Primaquine is not recommended for prevention, Metronidazole is used for bacterial and parasitic infections but not malaria, Pyrimethamine is used in combination with sulfadoxine for treatment but not prevention, Chloroquine is not effective against chloroquine-resistant strains, and Quinine is used for treatment but not prevention of malaria.

6. A 41-year-old woman, coming back from a trip to Kenya, was admitted to the hospital because of malaise, myalgia, abdominal pain and fever (104E F). The recent history of the patient was significant for two paroxysmal attacks of chills, fever and vomiting. The first attack lasted a day and was followed by a second 36 hours later. Physical examination revealed an acutely hill patient complaining of severe abdominal pain. Palpation showed a tender, soft and enlarged spleen. Examination of a stained blood specimen revealed ringlike and crescent-like forms within the RBCs. Which of the following pairs of drugs would be appropriate for this patient?

Quinidine and doxycycline

Primaquine and clindamycin

Pyrimethamine and metronidazole

Chloroquine and paromomycin

Mefloquine and ciprofloxacin

The patient's symptoms and physical examination findings are consistent with a diagnosis of malaria, specifically caused by Plasmodium falciparum. The presence of ringlike and crescent-like forms within the red blood cells confirms this. Quinidine and doxycycline are appropriate treatment options for severe P. falciparum malaria. Quinidine is a medication that is used to treat severe malaria by killing the parasite, while doxycycline is an antibiotic that is effective against the malaria parasite. Therefore, the combination of quinidine and doxycycline would be appropriate for this patient.

Explanation

The patient's symptoms and physical examination findings are consistent with a diagnosis of malaria, specifically caused by Plasmodium falciparum. The presence of ringlike and crescent-like forms within the red blood cells confirms this. Quinidine and doxycycline are appropriate treatment options for severe P. falciparum malaria. Quinidine is a medication that is used to treat severe malaria by killing the parasite, while doxycycline is an antibiotic that is effective against the malaria parasite. Therefore, the combination of quinidine and doxycycline would be appropriate for this patient.

7. A 55-year-old man, who was about to leave for a vacation trip to central Africa, started a treatment with mefloquine. Which of the following plasmodia cells can be effectively killed by the drug?

P. Vivax hypnozoites

P. Falciparum gametocytes

P. Vivax tissue schizonts

P. Falciparum hypnozoites

P. Malarie blood schizonts

P. Malarie tissue schizonts

Mefloquine is an effective drug for killing P. Malariae blood schizonts.

Explanation

Mefloquine is an effective drug for killing P. Malariae blood schizonts.

8. A 43-year-old man is about to leave for a vacation trip to central America. He is advised by his physician to take mefloquine as a prophylactic measure, since he knew that chloroquine resistance was widespread and increasing. Which of the following phrase best explains the likely mechanism of plasmodial resistance to chloroquine?

Increased inactivation of the drug

Increased activity of DNA repair mechanism

Increased drug transport outside plasmodia cells

Decreased chloroquine binding sites on plasmodia cells

Decreased of conversion of free heme into hemozoin

The likely mechanism of plasmodial resistance to chloroquine is increased drug transport outside plasmodia cells. This means that the plasmodia cells are able to effectively remove the chloroquine from their cells, reducing its effectiveness in killing the parasites. This resistance mechanism allows the parasites to survive and continue to cause malaria despite the presence of chloroquine.

Explanation

The likely mechanism of plasmodial resistance to chloroquine is increased drug transport outside plasmodia cells. This means that the plasmodia cells are able to effectively remove the chloroquine from their cells, reducing its effectiveness in killing the parasites. This resistance mechanism allows the parasites to survive and continue to cause malaria despite the presence of chloroquine.

9. A 33-year-old man was planning a vacation to sub-Saharan Africa where chloroquineresistant strains of P. falciparum are present. Which of the following drugs combinations would be appropriate to prevent infection in this man?

Primaquine-quinine

Mefloquine-metronidazole

Pyrimethamine-sulfadoxine

Doxycycline-iodoquinol

Chloroquine-paromomycin

Pyrimethamine-sulfadoxine would be an appropriate drug combination to prevent infection in this man. Pyrimethamine is a medication that inhibits the growth of the parasite, while sulfadoxine is an antibiotic that prevents the parasite from reproducing. This combination is effective against chloroquine-resistant strains of P. falciparum, which are commonly found in sub-Saharan Africa.

Explanation

Pyrimethamine-sulfadoxine would be an appropriate drug combination to prevent infection in this man. Pyrimethamine is a medication that inhibits the growth of the parasite, while sulfadoxine is an antibiotic that prevents the parasite from reproducing. This combination is effective against chloroquine-resistant strains of P. falciparum, which are commonly found in sub-Saharan Africa.

10. A 24-year-old woman, who was 22-week pregnant, presented with a 5-day history of loose stools containing bloody mucus. Her past medical history was significant for an optic neuritis one month ago, apparently due to a viral infection. Upon physical examination her abdomen was soft but nontender. The exam of fresh stools showed E. histolytica trophozoites. A CT scan was negative for gut wall or liver amebiasis. Which of the following drugs would be appropriate for this patient?

Metronidazole

Chloroquine

Clindamycin

Paromomycin

Pyrimethamine

Sulfadoxine

Paromomycin would be the appropriate drug for this patient because it is effective against E. histolytica, the parasite causing the symptoms of loose stools containing bloody mucus. Metronidazole is also effective against E. histolytica, but it is contraindicated in pregnancy. Chloroquine is used for the treatment of malaria, not amebiasis. Clindamycin is not effective against E. histolytica. Pyrimethamine and sulfadoxine are used for the treatment of malaria, not amebiasis. Therefore, Paromomycin is the most appropriate choice for this pregnant patient with amebiasis.

Explanation

Paromomycin would be the appropriate drug for this patient because it is effective against E. histolytica, the parasite causing the symptoms of loose stools containing bloody mucus. Metronidazole is also effective against E. histolytica, but it is contraindicated in pregnancy. Chloroquine is used for the treatment of malaria, not amebiasis. Clindamycin is not effective against E. histolytica. Pyrimethamine and sulfadoxine are used for the treatment of malaria, not amebiasis. Therefore, Paromomycin is the most appropriate choice for this pregnant patient with amebiasis.