Resp - TB Pharma

Question 1

describe the drug regimen used to treat active TB

Answer 1

1. 6 mths RIFAMPICIN
2. 6 mths ISONIAZID
3. 2 mths PYRAZINAMIDE
4. 2 mths ETHAMBUTOL

Question 2

which monitoring tests must be performed before and during treatment?

Answer 2

1. LFTs: assess liver function before drug Tx as rifampicin, isoniazid and pyrazinamide associated with liver toxicity. Those with pre-existing liver disease or alcohol dependence should have frequent checks, esp. in 1st 2 mths.
2. UandEs and creatinine: assess renal function before drug Tx and make appropriate dose adjustments. Avoid ethambutol in pts with renal impairment if possible (if used, dose should be reduced and plasma conc. monitored)
3. Visual acuity (Snellen chart): test before Tx with ethambutol as can cause visual disturbances.

Question 3

what is the MOA of rifampicin?

Answer 3

RNA synthesis suppression - inhibits RNA polymerase activity.

Question 4

suggest possible ADRs of rifampicin

Answer 4

1. hepatitis (check LFTs before prescribing)
2. reddish colouration of urine, sweat, sputum and tears
3. anorexia, nausea, vomiting, abdo. discomfort, diarrhoea
4. thrombocytopenia +/- purpura
5. severe, systemic hypersensitivity reactions (fever, lymphadenopathy, rash)
6. acute renal failure (ATN or acute interstitial nephritis)

Question 5

what is the MOA of isoniazid?

Answer 5

Pro-drug activated by Mtb catalase peroxidase enzyme KatG - inhibits synthesis of mycolic acids (cell wall) by blocking action of fatty acid synthase.

Question 6

suggest possible ADRs of isoniazid. How can 1 of these be reduced?

Answer 6

1. hepatitis, jaundice
2. peripheral neuropathy and optic neuritis - give with vit B6 to prevent nerve damage
3. constipation, nausea, vomiting
4. acute pancreatitis
5. elevated mood, psychotic disorder
6. gynaecomastia
7. Stevens-Johnson syndrome

Question 7

what is the MOA of pyrazinamide?

Answer 7

Pro-drug activated by Mtb pyraxinamidase - inhibits synthesis of fatty acids by blocking action of fatty acid synthase

Question 8

suggest possible ADRs of pyrazinamide

Answer 8

1. arthralgia (most common)
2. hepatitis (most common cause of drug-induced hepatitis of RIPE)
3. gout flares (decreases renal excretion of uric acid) - gout is a CI
4. anorexia, nausea and vomiting
5. malaise and fever
6. sideroblastic anaemia
7. hypersensitivity reactions, e.g. urticaria, pruritis and rashes

Question 9

what is the MOA of ethambutol?

Answer 9

inhibits cell wall synthesis and increases cell wall permeability by binding to arabinogalactan and inhibiting arabnosyl transferase

Question 10

suggest possible ADRs of ethambutol

Answer 10

1. visual disturbances: loss of acuity inc. irreversible blindness (due to optic neuritis), colour blindness, restriction of visual fields
2. hepatitis
3. arthralgia
4. anorexia, vausea, vomiting
5. peripheral neuropathy
6. gout flares (decreases renal excretion of uric acid)
7. fever, malaise, headache and dizziness