Folate Antagonists - 2.3

Question 1

What is involved in reactions involving the transfer of one carbon unit essential for DNA & RNA synthesis?

Answer 1

Folic Acid

Question 2

Difference between humans and bacteria in acquiring folate:

Answer 2

Humans have to supplement in diet, while bacteria synthesize own folate from precursors such as PABA

Question 3

MOA of Sulfonamides

Answer 3

Binding to Dihydropteroate Synthase competitively

Question 4

MOA of Trimethoprim/Methotrexate/Pyrimethamine

Answer 4

Inhibition of Dihydrofolate Reductase; bacteria most sensitive to Trimethoprim, humans most sensitive to Methotrexate

Question 5

MOA of 5-Fluorouracil/Flucytosine

Answer 5

Blockage of Thymidilate Synthase

Question 6

What does Sulfadoxine treat?

Answer 6

Malaria

Question 7

What does Dapsone treat and what class is it?

Answer 7

Leprosy; Sulfonamide

Question 8

What does Sulfasalazine treat?

Answer 8

Ulcerative Colitis

Question 9

What is the resistance mechanism for Sulfonamides?

Answer 9

1. Increased PABA Synthesis
2. Altered Enzyme (DH Synthase can undergo mutation)
3. Decreased Uptake

Question 10

What are Sulfonamides used to treat?

Answer 10

Drug of choice for Nocardia infections; alternative Rx in Chlamydia & Trachomatis

Question 11

What are adverse reactions of Sulfonamides?

Answer 11

1. Hypersensitivity: Rashes that can be severe
2. Renal Calculi: White colored urine; crystalluria
3. Hemolysis in G6PD Patients
4. Kernicterus in newborns if given 3rd trimester
5. Increased drug-drug interactions so increase levels of methotrexate, phenytoin, and warfarin

Question 12

What loop diuretic does not have sulfa structure?

Answer 12

Ethacrynic Acid

Question 13

What are the trigger drugs and trigger food to worsen G6PD?

Answer 13

1. Food: Fava beans

2. Drugs: Anti-Malarials (Primaquine, Chloroquine), Anti-TB (Isoniazid), Sulfonamides (Mafenide, Cotrimoxazole)

Question 14

What’s the adverse reactions of Trimethoprim?

Answer 14

Very rarely can cause megaloblastic anemia due to folate deficiency, but usually doesn’t due to it’s ability to kill bacteria at therapeutic dose.

Question 15

What can reverse the adverse effects of Trimethoprim?

Answer 15

Leucovorin (Folinic Acid)

Question 16

What is Cotrimoxazole composed of?

Answer 16

Sulfamethoxazole & Trimethoprim; Individually bacterostatic but together bacterocidal the ratio is 5:1

Question 17

What are the ADR of Cotrimoxazole?

Answer 17

In pregnancy if given in the first trimester, cause NTD so avoid 12 weeks before pregnancy as well, in third trimester cause kernicturus and pre-term labor

Question 18

What are the contraindications of Cotrimoxazole?

Answer 18

Neonates up to 6 weeks
Liver failure/hepatitis
Renal insufficiency
Hypersensitivity to either individual component

Question 19

What is Cotrimoxazole used in?

Answer 19

1. Pneumocystis jiroveci
2. Nocardia
3. G- UTI for 3 days

Question 20

What is Sulfadiazine + Pyrimethamine used to treat?

Answer 20

1. Toxoplasma gondii

2. Leishmaniasis

Question 21

What is Sulfadoxine + Pyrimethamine used to treat?

Answer 21

Malaria

Question 22

What are the symptoms of Pneumocystis pneumonia?

Answer 22

Cough and Fever
CD <100/mm3
Exertional Dyspnea, PaO2 decrease (not compatible with X-Ray findings)

Question 23

What are the symptoms of Toxoplasma gondii?

Answer 23

Acute symptoms similar to flue.
Latent form and psychiatric manifestations can be seen
Transmitted by cats, cause ring enhancing lesion (abscess)