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Antimicrobials > Anti-tuberculosis agent > Flashcards

Anti-tuberculosis agent Flashcards

1
Q

What are the first line drugs against tuberculosis?

A

(RIPES)

Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin
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2
Q

When to initiate treatment for TB?

A

Sputum for Ziehl-Neelsen stain for acid fast bacilli is positive

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3
Q

What are the confirmatory tests for TB

A

4-8 weeks to grow & confirm TB

4-6 weeks to test for drug susceptibility

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4
Q

What’s the treatment regimen for TB?

A

2 months of RIPES (intensive) + 4 months daily RI

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5
Q

What are the general adverse effects of TB therapy to look out for?

A
  1. cutaneous rxn (anti-histamine other stop drug SJS TEN)

2. GI symptoms (*impt to dx if it is hepatotoxicity symptoms)

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6
Q

What are the drugs that can target both metabolically active & stationary phase bacilli?

A
  1. Rifampicin
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7
Q

What is the mechanism of action of rifampicin?

A

Rifampicin inhibits gene transcription of mycobacteria by blocking the *DNA-dependent RNA polymerase, which prevents the bacillus from synthesizing messenger RNA and protein, causing cell death.

  • resistance= mutation of DNA dependent RNA polymerase of mycobacteria
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8
Q

State 2 clinical indications for rifampicin

A
  1. Latent / Active tuberculosis

2. Leprosy, against Mycobacterium leprae

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9
Q

Name 3 adverse effects associated with rifampicin

A
  1. Hepatitis
  2. Cutaneous reactions
  3. Gastrointestinal symptoms
  4. orange staining of fluids (like nitrofurantoin stains urine brown)
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10
Q

Which of the 4 standard first line anti-tuberculosis drugs are safe for use in patients with kidney failure?

A

Rifampicin and Isoniazid

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11
Q

What is the mechanism of action of isoniazid?

A

Isoniazid is activated by the *catalase-peroxidase enzyme of M. tuberculosis. The activation of isoniazid produces *oxygen-derived free radicals that can inhibit the formation of *mycolic acids of the bacterial cell wall, cause *DNA damage and, subsequently, the death of the bacillus.

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12
Q

Which enzyme is involved in the metabolism of isoniazid, and presents with wide variation in activity in the community due to genetic polymorphisms?

A

N-acetyl transferase
(rapid acetylator vs slow acetylator phenotypes are found in the population due to the genetic polymorphism)

(Chinese faster than indians)

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13
Q

What are the 2 liver metabolites of isoniazid and which is toxic?

A

Acetyl hydrazine & hydrazine (toxic- via amidase)

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14
Q

State 2 adverse effects related to isoniazid

A
  1. Peripheral Neuropathy

2. Hepatitis

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15
Q

Why does isoniazid manifest as peripheral neuropathy?

A

competitive inhibitor of pyridoxine metabolism –> Deficiency of active vit B6

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16
Q

What food – food interactions must patients taking isoniazid be aware for?

A

They should avoid food rich in tyramine and histamine (certain types of fish, cheese and red wine).
as isoniazid inhibits MAO & histaminase–>flushing headache

17
Q

Indications for isoniazid

A
  1. active
  2. latent TB
  3. prophylaxis
18
Q

Patients on isoniazid are often co-administered _________ to help overcome ________ deficiency to avoid peripheral ________ .

A

pyridoxine, vitamin B6, neuropathy

19
Q

In which groups of patients do you have to adjust dose?

A

PE– renal impairment

P- avoid in hepatic impairment

20
Q

Drug drug interactions of RIPE

A

R- inducer of CYP450

I & P- inhibitor of CYP450

21
Q

Which of RIPE are prodrugs?

A

Isoniazid & pyrazinamide

22
Q

Which of the 4 standard first line anti-tuberculosis drugs must be avoided or used with caution if the patient suffers from liver disease?

A

(RIP)

Rifampicin
Isoniazid
Pyrazinamide

23
Q

What is the mechanism of action of pyrazinamide?

A

Pyrazinamide is converted to its active form, pyrazinoic acid, by pyrazinamidase. The accumulation of pyrazinoic acid decreases the intracellular pH to levels that cause the inactivation of critical pathways necessary for the survival of the bacteria.

24
Q

Which of the first line anti-tuberculosis drugs is highly effective against the **persistent bacilli resulting in bacteriological relapse?

A

Pyrazinamide

potent sterilising effect in acid medium w/in macrophages & at acute inflm sites

25
Q

Is there cross resistance b/n pyrazinamide & isoniazid due to similar moleculr str?

A

No cross resistance w pyrazinamide & isoniazid

26
Q

Adverse effects of pyrazinamide

A
  1. Hepatotoxicity
  2. Hyperuricemia– pyrazinoic acid
  3. Arthralgia
27
Q

Which of the 4 standard first line anti-tuberculosis drugs (R.I.P.E) is/are highly associated with causing gout like symptoms?

A
  1. Pyrazinamide (More common with pyrazinamide then ethambutol)
  2. Ethambutol
28
Q

Which of the 4 standard first line anti-tuberculosis drugs must be avoided or used with caution if the patient suffers from kidney impairment?

A
  1. Pyrazinamide

2. Ethambutol

29
Q

What is the mechanism of action ethambutol?

A

Ethambutol inhibits the arabinosyltransferase enzyme (embB gene) and interferes with the polymerization of arabinose into arabinogalactan, the principal polysaccharide on the mycobacterial cell wall.

30
Q

What are the adverse effects of ethambutol?

A
  1. Visual toxicity
    (so shld do baseline visual acuity test + colour vision test & monitor progress)
  2. Gout/ hyperuricemia
31
Q

Which class of antibiotics does streptomycin belong to?

A

Aminoglycoside

32
Q

How is streptomycin administered?

A

Intramuscular injection

33
Q

How is streptomycin used in TB?

A

Intensive phase may be used in place of ethambutol

34
Q

Adverse effects of streptomycin

A

“NO”: Neurotoxocity & Nephrotoxicity + Ototoxicity (shld not be used w NO drugs)

35
Q

In which groups of individuals would physicians have a high index of suspicion for multi drug-resistant tuberculosis?

A

Individuals

  1. who were previously treated for TB,
  2. who have failed TB treatment,
  3. who are known contacts of patients with MDR-TB, or
  4. who come from countries with high prevalence of drug resistant tuberculosis (India Philippines, russia, south Africa)
  • MDR-TB: resistance to rifampicin & isoniazid**
36
Q

What does extensively drug resistant TB refer to?

A

MDR TB w additional resistance to any fluoroquinolones & second line injectable agents (2 key second line drugs)

37
Q

What does cure of TB mean?

A
  1. negative sputum smear or culture in last month of treatment & at least one previous occasion
38
Q

Treatment failure means…

A

positive sputum bacteriology at or after 5 months of treatment

39
Q

What is a good surrogate marker for risk of relapse?

A

Non conversion of sputum cultures at 2 months

Antimicrobials (11 decks)

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