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Old 04-09-2011
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Drug Why do we give multiple medications

A 43-year-old Puerto Rican male presents to his primary care physician with complaints of fever, chills, night sweats, and a 4 kg (10 lb) weight loss in the last 3 months. He also has a cough productive of yellow sputum. He has a history of HIV infection (last CD4+ count = 500 / mm3). Sputum smear stained with the Ziehl-Neelsen method demonstrates acid-fast bacilli. Pending culture results, the patient is prescribed 4 medications. Why is treatment with multiple medications necessary?

A) Anticipated noncompliance with treatment
B) Due to the patient's HIV status
C) Extreme virulence of the isolate
D) High frequency of mutational resistance
E) High rate of medication side effects
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Old 04-09-2011
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This patient has TB so I would say C, high virulence.

I never really thought about why we give so many drugs, I kinda just accepted it. Good question

Side note: Vitamin B6 deficiency (often associated with Isoniazid therapy) can lead to sideroblastic anemia! Recall that Vit B6 is a cofactor for the rate limiting step in heme synthesis catalyzed by ALA synthase --> Leads to buildup of iron in mitochondria and thus sideroblastic anemia. Just read about it and wanted to pass on the knowledge
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I seem to remember giving multiple drugs for TB is to prevent resistance.
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Old 04-10-2011
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My ans is D) High frequency of mutational resistance

This is a great qn, USMLE type qn. You should know the MOA of resistance. This is a HY part of anti-TB drugs.
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Old 04-10-2011
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Quote:
Originally Posted by apx85 View Post
This patient has TB so I would say C, high virulence.

I never really thought about why we give so many drugs, I kinda just accepted it. Good question

Side note: Vitamin B6 deficiency (often associated with Isoniazid therapy) can lead to sideroblastic anemia! Recall that Vit B6 is a cofactor for the rate limiting step in heme synthesis catalyzed by ALA synthase --> Leads to buildup of iron in mitochondria and thus sideroblastic anemia. Just read about it and wanted to pass on the knowledge
Pyridoxine deficiency will lead to neuropathy (along with sideroblastic anemia) which ofcourse is higher yield!

I would say it is to prevent resistance. M.tb, on single drug program will be resistant very fast.
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Old 04-10-2011
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D. Resistance
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Old 04-10-2011
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Default Right guys

Right guys, you got the right answer.
It's the resistance of tuberculosis.

If we fail in treating a patient, that patient might transmit the infection to others and the TB epidemic grows larger.
If you give four drugs there's less chance that the bacteria are resistant to all them than in the case when you give one drug.

Spontaneous (mutational resistance) is very common in the TB bacteria.
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Old 04-10-2011
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Some key points from my notes...

Rifampicin - B-subunit of RNA polymerase

Isoniazid - Catalase-peroxidase or Alky hydro-reductase

INH-Ethionamide - Enoyl-ACP reductase

Streptomycin - Ribosomal protein S12 or 16s rRNA

Fluoroquinolone - DNA gyrase

Pyrazinamide - Amidase

Ethambutol - EmbCAB
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