Anti-Mycobacterial Therapy Flashcards

1
Q

What is the general idea in drug therapy of TB?

A

Multiple drugs are used

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2
Q

Isoniazid HCl MOA

A
  • Isoniazid is a “prodrug” that is activated by catalase peroxidase, which is regulated by the TB katG gene
  • Targets the TB inhA gene product – enoyl- reductase – and therefore inhibits synthesis of mycolic acid in the TB cell wall
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3
Q

Isoniazid HCl Resistance Mechanisms

A
  • Mutations in katG gene result in inactivation of catalase-peroxidase
  • Mutation in regulatory region of inhA gene, which is involved in mycolic acid synthesis
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4
Q

Isoniazid HCl Metabolism

A

INH acetylation in liver by N-acetyltransferase - rate is dependent upon genetics

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5
Q

Does INH cross the BBB?

A

Yes - CSF levels 20% plasma levels but may equal

plasma levels with meningeal inflammation

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6
Q

Isoniazid HCl SE

A
  • Hepatotoxicity
  • Neurotoxicity
  • Hypersensitivity Reactions
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7
Q

How is a diagnosis of TB made?

A
  • PPD skin test is shown to be positive
  • The Hx will then be reviewed for any signs of risk factors
  • Presence of risk factors will prompt a CXR
  • Abnormal CXR will lead to AFB of the sputum for mycobacteria
  • Positive AFB will the lead to the NAAT test for TB
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8
Q

What are the drug interactions of INH?

A

• INH + rifampin increases occurrence of hepatitis

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9
Q

Rifampin MOA

A

Inhibits DNA-dependent RNA polymerase encoded by the rpoB gene

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10
Q

Rifampin Resistance Mechanisms

A

Mutations in the rpoB gene will grant resistance

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11
Q

Does rifampin cross the BBB into the CNS?

A

Yes it penetrates well

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12
Q

Rifampin SE

A
  • Hepatotoxicity increased with other hepatotoxic drugs like INH
  • Red discoloration of body fluids – urine, tears, soft contacts
  • Acute renal failure, interstitial nephritis
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13
Q

What are the drug interactions of rifampin?

A

Induces hepatic microsomal enzymes - interacts with hundreds of drugs

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14
Q

What is the clinical use of ethambutol?

A

A “helper” drug that inhibits resistance to other drugs

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15
Q

Ethambutol MOA

A

Inhibits synthesis mycobacterial arabinosyl transferase encoded by embB which affects wall synthesis

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16
Q

Does ethambutol cross the BBB into the CNS?

A

No - very poorly even with inflammation

17
Q

Ethambutol SE

A
  • Optic neuritis

- Peripheral neuropathy

18
Q

What is the clinical use of pyrazinamide?

A

First line TB drug – for the 1st two months of therapy - increases the cure rate and reduces the likelihood of relapse

19
Q

Pyrazinamide MOA

A

A “prodrug” activated by TB pyrazinamidase, encoded by pncA

20
Q

Does pyrazinamide cross the BBB into the CNS?

A

Distribution is good, including in the CSF in tuberculous meningitis

21
Q

Pyrazinamide SE

A
  • Hepatitis, worse in patients with preexisting liver disease
  • Skin rash and gastrointestinal intolerance
  • Increased serum uric acid levels, but acute gout is uncommon
22
Q

What is the clinical use of streptomycin in TB?

A

Second line TB drug

23
Q

Streptomycin MOA

A

Inhibits protein synthesis by binding to ribosome

24
Q

Streptomycin SE

A
  • Ototoxicity

- Nephrotoxicity

25
Q

What is primary TB resistance?

A

Infection by a source case with drug-resistant TB - acquired with the infection

26
Q

What is secondary TB resistance?

A

From ineffective therapy causing resistance to develop during treatment

27
Q

Why is multi drug therapy used in cases of TB?

A

Risk of evolution of resistance to two drugs is the product of the risk of the development of resistance to each drug - FAR lower

28
Q

What is multi-drug resistant TB?

A

Resistance to both INH and rifampin - more common in those with HIV

29
Q

What is extensively drug resistant TB?

A
  • Resistance to INH and Rifampin
  • Resistance to a fluoroquinolone antibiotic
  • Resistance to one of three injectable antibiotics (amikacin, kanamycin, capreomycin)
30
Q

What is the problem with therapy in MDR-TB?

A

Requires therapy for at least 18-24 months because rifampin resistance eliminates the short course therapy

31
Q

What is the 6 month TB treatment regimen?

A
  • 4-drug regimen (“RIPE” therapy = Rifampin-INH-PZA-Ethambutol)
  • Initial phase: RIPE
  • Continuation phase: RI (Note: Emb not needed if pan-suceptible)
32
Q

How is intermittent treatment of TB administered (2-3 times a week)?

A

Directly Observed Therapy

33
Q

Why is rifampin resistance so important clinically?

A

Loss of rifampin from the regimen means loss of the option for short-course (6 month) TB therapy

34
Q

What are some of the treatments for latent TB infection?

A
  • INH monotherapy for 9 months is highly effective

- Rifampin – 4 month, daily therapy

35
Q

What are the drugs that are unique to NTM treatment?

A
  • Clarithromycin

- Azithromycin

36
Q

What drugs are used for both TB and NTM?

A
  • Rifampin
  • Ethambutol
  • FQs
  • AGs
37
Q

Is the treatment of leprosy different than that of TB?

A

Yes. Leprosy treatment is different treatment from TB treatment.

38
Q

Paucibacillary Leprosy Treatment

A

Rifampin + dapsone daily for 12 months

39
Q

Multibacillary Leprosy Treatment

A

Rifampin + dapsone + clofazimine daily for 24 months