Anti TB Drugs

Question 1

1st line drugs

Answer 1

• Isoniazid (H)
• Rifampicin (R)
• Pyrazinamide (Z)
• Ethambutol (E)
• Streptomycin (S)

Question 2

2nd line drugs

Answer 2

• Aminoglycosides
• Capreomycin
• Cycloserine
• PAS (Para amino salicylic acid)

Question 3

2nd line drugs usage

Answer 3

• Patient who cannot tolerate 1st line drugs

* Patients with resistant TB

Question 4

TB treatment

Answer 4

1st phase (Initial bactericidal phase): 2 months of EHRZ
2nd phase (Continuation sterilising phase): 4 months of HR

Question 5

Rifampicin MOA

Answer 5

• Binds to beta subunit of RNA polymerase and blocks RNA synthesis

Question 6

Rifampicin PK

Answer 6

• Given orally
• High fat meal increases AUC by 50%
• Metabolised and excreted in bile, feces, urine
• Crosses placenta

Question 7

Rifampicin therapeutic use

Answer 7

• Tuberculosis

* Leprosy (mycobacterium leprae)

Question 8

Rifampicin ADR

Answer 8

• Skin rash
• Nausea and vomiting
• Fever
• Hepatitis
• Allergy: haemolysis, flu-like, renal damage
• Orange/red colour to urine, sweat, saliva
• Red man syndrome with overdose

Question 9

Rifampicin drug interactions

Answer 9

• Induces liver CYP enzymes - increases metabolism of digoxin, quinidine, corticosteroids etc

Question 10

Pyrazinamide

Answer 10

• Inhibits cell membrane synthesis

* Activated to form POAH -> acidify extra cellular milleu -> inhibits enzyme function -> kill bacteria

Question 11

Pyrazinamide PK

Answer 11

• Well absorbed, wide distribution, concentrated in lung

* Excreted by kidney

Question 12

Pyrazinamide adverse effects

Answer 12

• Hepatitis
• Hyperuricaemia
• Athralgia
• GI: nausea, vomiting, diarrhea

Question 13

Isoniazid MOA

Answer 13

• Inhibits synthesis of mycolic acid -> cell death

Question 14

Isoniazid PK

Answer 14

• Rapid absorption
• Enters CNS
• Excreted in urine in 24hr

Question 15

Isoniazid ADR

Answer 15

• Hepatitis
• Peripheral neuritis
• CNS: convulsion, optic neuritis, dizziness
• Allergy: vasculitis, arthritis, skin lesions, SLE

Question 16

Isoniazid drug interaction

Answer 16

• Inhibit CYP2C19, CYP3A, CYP2D6

* Increase toxicity of theophylline

Question 17

Ethambutol MOA

Answer 17

Inhibits arabinosyl transferase III -> disrupts assembly of cell wall

Question 18

Ethambutol PK

Answer 18

• Bioavailability ~80% after oral administration
• Widely distributed, not metabolised
• > 80% excreted unchanged in urine

Question 19

Ethambutol ADR

Answer 19

• Optic neuritis (decreased visual acuity, inability to differentiate red/green)
• Rash
• GI upset
• Peripheral neuritis

Question 20

Aminoglycosides examples

Answer 20

• Amikacin

* Kanamycin

Question 21

Aminoglycosides MOA

Answer 21

• Inhibits protein synthesis by binding with 30S ribosomal subunit and causing misreading of genetic code during translation

Question 22

Aminoglycosides PK

Answer 22

• Water soluble, highly polar, poor GI absorption
• Given parenterally
• Excreted in urine

Question 23

Aminoglycosides ADR

Answer 23

• Ototoxic: vertigo, deafness

* Nephrotoxic: renal damage

Question 24

Aminoglycosides CI

Answer 24

Pregnancy (deafness in infants)

Question 25

Capreomycin properties

Answer 25

* Peptide protein synthesis inhibitor | * Given by injection

Question 26

Capreomycin ADR

Answer 26

* Nephrotoxic | * Ototoxic

Question 27

Cycloserine MOA

Answer 27

Inhibit cell wall synthesis

Question 28

Cycloserine ADR

Answer 28

* Peripheral neuropathy * Depression * Psychosis

Question 29

PAS MOA

Answer 29

* Folate synthesis antagonist * Bacteriostatic * Active exclusively against M. tuberculosis

Question 30

PAS ADR

Answer 30

* GI upset | * Allergy: fever, joint pain, skin rash, hepatitis, jaundice

Question 31

Atypical mycobacteria

Answer 31

• M. avium complex infection observed in immunocompromised patient

Question 32

Atypical mycobacteria treatment

Answer 32

* Triple drug therapy: clarithromycin/azithromycin, rifampin, ethambutol * 3 times a week for 12 months * In cavitatory disease: inj amikacin/streptomycin can be added as 4th drug