CH5 | Antimycobacterial Drugs

Question 1

What shape are Mycobacteria?

Answer 1

Rod-shaped aerobic bacilli.

Question 2

How do Mycobacteria multiply?

Answer 2

They multiply slowly.

Question 3

What is a significant characteristic of Mycobacteria regarding resistance?

Answer 3

They have a high ability to develop resistance.

Question 4

Where can Mycobacteria reside within the human body?

Answer 4

Within macrophages. This makes them “intracellular pathogens”.

Question 5

What essential component is found in the cell wall of Mycobacteria?

Answer 5

Mycolic acid.

Question 6

What type of acids make up mycolic acid?

Answer 6

Long-chain, β-hydroxylated fatty acids.

Question 7

What is a characteristic of the mycobacterial cell wall?

Answer 7

It is lipophilic and lipid-rich.

Question 8

What type of lesions do mycobacterial infections cause?

Answer 8

Slow-growing, granulomatous lesions, causing tissue destruction throughout the body.

Question 9

Which part of the body is mostly affected by Mycobacterial infections?

Answer 9

The lungs.

Question 10

What disease is primarily caused by Mycobacterium tuberculosis?

Answer 10

Tuberculosis (TB).

Question 11

Which pathogen causes Tuberculosis (TB)?

Answer 11

Mycobacterium tuberculosis.

Question 12

What condition occurs when a patient is infected with M. tuberculosis but shows no signs or symptoms?

Answer 12

Latent tuberculosis infection (LTBI).

Question 13

Where do dormant mycobacteria reside in a patient with LTBI?

Answer 13

Within macrophages.

Question 14

What are the four first-line drugs used in TB treatment?

Answer 14

Isoniazid, rifampin, pyrazinamide, and ethambutol.

Question 15

When are second-line drugs used in TB treatment?

Answer 15

When first-line drugs are ineffective (resistant TB) or the patient cannot tolerate first-line drugs.

Question 16

Name the classes of second-line drugs used in TB treatment.

Answer 16

Aminoglycosides, fluoroquinolones, cycloserine, and macrolides.

Question 17

What is the role of cycloserine in TB treatment?

Answer 17

It is used as a second-line drug when first-line drugs are ineffective or intolerable.

Question 18

What type of drug are macrolides considered in the context of TB treatment?

Answer 18

They are second-line drugs.

Question 19

What is the reason for the long duration of TB treatment?

Answer 19

Due to the slow growth of M. tuberculosis, treatment ranges from months to years.

Question 20

What is the duration of treatment for LTBI with isoniazid monotherapy?

Answer 20

9 months.

Question 21

How long is the treatment duration for multidrug-resistant TB (MDR-TB)?

Answer 21

2 years.

Question 22

What is the minimum treatment duration for TB?

Answer 22

At least 6 months.

Question 23

What is required for the treatment of TB or MDR-TB?

Answer 23

They must be treated with multiple drugs.

Question 24

What is the treatment approach for MDR-TB?

Answer 24

Use second-line drugs plus any effective drug from the first line.

Question 25

What is Isoniazid considered in the treatment of tuberculosis (TB)?

Answer 25

The most active drug for the treatment of TB caused by susceptible strains.

Question 26

What type of drug is Isoniazid?

Answer 26

A prodrug that is activated by mycobacterial catalase-peroxidase (KatG).

Question 27

What enzymes does the active form of Isoniazid target?

Answer 27

Acyl carrier protein reductase (InhA) and β-ketoacyl-ACP synthase (KasA).

Question 28

What is the effect of Isoniazid on mycolic acid synthesis?

Answer 28

It inhibits mycolic acid synthesis.

Question 29

What is the mechanism of action (MOA) of Isoniazid?

Answer 29

Inhibits mycolic acid synthesis by targeting enzymes required for its synthesis.

Question 30

What is the bactericidal property of Isoniazid?

Answer 30

It is bactericidal against rapidly growing cells and intracellular organisms.

Question 31

What are the resistance mechanisms associated with Isoniazid?

Answer 31

Resistance can occur due to mutation or deletion of KatG, mutations of acyl carrier proteins, and overexpression of InhA.

Question 32

How is Isoniazid absorbed in the body?

Answer 32

Isoniazid is readily absorbed after oral administration.

Question 33

When should Isoniazid be taken for optimal absorption?

Answer 33

Isoniazid should be taken on an empty stomach.

Question 34

Where does Isoniazid diffuse in the body?

Answer 34

It diffuses into all body fluids and cells, including the cerebrospinal fluid (CSF).

Question 35

What metabolic processes does Isoniazid undergo?

Answer 35

Isoniazid undergoes n-acetylation and hydrolysis.

Question 36

How is Isoniazid excreted from the body?

Answer 36

It is excreted through glomerular filtration and secretion.

Question 37

What are the adverse effects of Isoniazid?

Answer 37

* Hepatitis (most serious side effect). * Peripheral neuropathy. * Convulsions. * Rashes. * Fever. * Drug-drug interactions.

Question 38

What drug interactions does Isoniazid have?

Answer 38

It inhibits the metabolism of carbamazepine and phenytoin.

Question 39

What are the consequences of drug interactions caused by Isoniazid?

Answer 39

Ataxia and nystagmus.

Question 40

What are the examples of Rifamycins?

Answer 40

Rifampin, rifabutin, and rifapentine.

Question 41

What is the mechanism of action (MOA) of Rifampin?

Answer 41

It blocks RNA transcription by interacting with mycobacterial DNA-dependent RNA polymerase.

Question 42

What is a key characteristic of Rifampin compared to Isoniazid?

Answer 42

Rifampin has a broader spectrum than Isoniazid, targeting different bacterial infections.

Question 43

What type of bacteria does Rifampin act against?

Answer 43

It is bactericidal and effective against intracellular and extracellular mycobacteria, as well as Gram-positive and Gram-negative organisms.

Question 44

What is a major resistance mechanism for Rifampin?

Answer 44

Mutations in RNA polymerase.

Question 45

How is Rifampin absorbed after oral administration?

Answer 45

It has adequate absorption.

Question 46

How does Rifampin distribute in the body?

Answer 46

It distributes to all body fluids and organs, with CSF concentrations being 10% to 20% of blood concentrations.

Question 47

What happens to Rifampin in the liver?

Answer 47

It is taken up by the liver and undergoes enterohepatic recycling.

Question 48

How is Rifampin eliminated from the body?

Answer 48

Mainly through bile into feces, with a small percentage in urine.

Question 49

What are the common adverse effects of Rifampin?

Answer 49

Nausea, vomiting, rash, gastrointestinal upset, flu-like syndrome (fever, chills, myalgia), and rare hepatitis and death.

Question 50

What should be noted about drug interactions with Rifampin?

Answer 50

Rifampin induces cytochrome P450 enzymes, which can decrease the effectiveness of drugs such as oral contraceptives, warfarin, and certain antiretrovirals.

Question 51

What is Pyrazinamide and how is it used?

Answer 51

It is a prodrug activated to pyrazinoic acid by mycobacterial pyrazinamidase. It is used for a short period in combination with other drugs.

Question 52

How is Pyrazinamide administered?

Answer 52

Orally.

Question 53

At what pH is Pyrazinamide active?

Answer 53

Active at low pH (5.5).

Question 54

What is the mechanism of action of pyrazinoic acid?

Answer 54

It disrupts mycobacterial cell membrane metabolism and transport functions.

Question 55

What role does Pyrazinamide play in tuberculosis treatment?

Answer 55

It acts as a sterilizing agent active against residual intracellular organisms that may cause relapse.

Question 56

What are some adverse effects of Pyrazinamide?

Answer 56

Nausea, hepatitis, hyperuricemia, rash, joint ache, and rare gout.

Question 57

How does Pyrazinamide exert its activity against mycobacteria?

Answer 57

It is taken up by macrophages and acts against mycobacteria within the acidic environment of lysosomes.

Question 58

What type of drug is Ethambutol?

Answer 58

Bacteriostatic and specific for mycobacteria.

Question 59

What is the mechanism of action of Ethambutol?

Answer 59

Inhibits arabinosyl transferases, involved in the polymerization reaction of arabinoglycan, which are required for the synthesis of the mycobacterial cell wall.

Question 60

How well does Ethambutol distribute throughout the body?

Answer 60

It distributes well, but does not achieve adequate concentrations for tuberculous meningitis.

Question 61

How is Ethambutol and its metabolites excreted?

Answer 61

Excreted in the urine.

Question 62

What are the adverse effects of Ethambutol?

Answer 62

Optic neuritis, diminished visual acuity (blurred vision), red-green color blindness, and decreased uric acid excretion.