Anti-metabolits and TB drugs

Question 1

Sulfonamides affect the _______ step of tetrahydrofolic acid synthesis whereas trimethoprim affect the ________ step

Answer 1

First, Second

Question 2

What compound do sulfonamide antimicrobial drugs try to mimic to compete for the active site of dihydropteroate synthetase?

Answer 2

Para-Aminobenzoic acid (PABA)

*bacteria have to form folic acid, we get it from diet

Question 3

What two folate synthesis enzymes are the target of inhibition?

Answer 3

1st step- Dihydropteroate synthetase

2nd step- Dihydrofolate reductase

Question 4

What are the two most common Sulfonamide antibiotics?

Answer 4

• Sulfamethoxazole (inhibits 1st step, systemic use)

- Silver sulfadiaxine (used as a topical usually in burns)

Question 5

Which sulfamethoxazole is bacteriostatic, no longer used as a mono therapy and is a competitive inhibitor of dihydropteroate synthetase?

Answer 5

Sulfamethoxazole (oral)

Question 6

Which combination drug is the first line treatment for Pneumocystis jiroveci (carinii) Pneumonia?

Answer 6

Cotrimoxazole (TMP/SMX)

*synergistic 1 part trimethoprim to 5 parts sulfamethoxazole

Question 7

What are the 3 extra bacterial defenses mycobacterium posses?

Answer 7

1. High lipid content of cell wall
2. Efflux pumps in cell membrane (pump out harmful chemicals)
3. Hide inside patient cells (mycobacterium avium)

Question 8

Which drug is the first line agent for TB and leprosy treatment and is a prophylactic drug for Meningococcal infection?

Answer 8

Rifampin

*4 R’s (RNA pol inhib, Revs CYP450, Red fluids, Rapid resistance on its own)

Question 9

Used as a TB prophylaxis, which drug must be activated by the TB catalase-oxidase enzyme, decreases mycolic acid synthesis and can be neurotoxic?

Answer 9

Isoniazid

*Neuron and hepatocyte injuries, Disulfiram like rxn with alcohol

Question 10

Which drug requires acidic pH to activate, is a mycolic acid inhibitor should not be used in pregnancy and can cause hepatotoxicity and gout?

Answer 10

Pyrazinamide

*bateriostatic

Question 11

Which drug is bacteriostatic, decreases carbohydrate polymerization by inhibiting arbinosol transferase, crosses the BBB and can cause blindness?

Answer 11

Ethambutol

Question 12

Which drug inhibits the 30 s subunit and can cause ototoxicity and deafness?

Answer 12

Streptomycin

*dont use in pregnancy

Question 13

Which drug inhibits mycobacterial ATP synthase and may cause headache or arthralgias?

Answer 13

Bedaquiline

*used for multi-drug resistant TB

Question 14

Which drug is a 50S inhibitor and may result in prolonged QT and acute cholestatic hepatitis?

Answer 14

Azithromycin (macrolide)

Question 15

Which drug inhibits bacterial dihydrofolate synthesis and is used for leprosy and prophylaxis against pneumocystis jirovecii?

Answer 15

Dapsone

Question 16

What are the two major mycobacterium related diseases?

Answer 16

1-Tuberculosis

2-Leprosy or Hansen’s disease

Question 17

What is the prophylactic treatment of choice and for how long for latent or asymptomatic TB patients?

Answer 17

Isoniazid for 9 months

Question 18

For an active TB infection, what is the treatment of choice?

Answer 18

• 2 months isoniazid, rifampin, ethambutol and pyrazinamide
• 4 months isoniazid and rifampin

*2 with 4, 4 with 2

Question 19

What is the treatment for secondary TB?

Answer 19

• 2 months of rifampin, izoniazid, pyrazinamide, ethambutol, PLUS STREPTOMYCIN
• 4 months of isoniazid and rifampin
• 2 with 5 then 4 with 2