Antimycobacterials Flashcards by Lauren F

What kind of cell does TB usually live in?

Macrophages

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What is the treatment of choice for erythema nodosum leprosum?

Thalidomide

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Why is ethambutol not recommended in children under 13?

Decrease of visual acuity and green-red perception.

However, this does not mean its contraindicated, you still need to give it for active TB. Just do regular eye exams

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What is the mechanism of action of streptomycin?

Inhibits 30s ribosome (its an aminoglycoside)

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What kinds of testing must you do on your patient before and during isoniazoid treatment?

Liver Function Tests

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What is erythema nodosum leprosum?

Fat pockets that are the symptom of leprosy

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What is the spectrum of ethambutol?

VERY narrow….it affects arabinogalactan, which is only in mycobacterium Tb

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What is another use for rifampin?

Leprosy

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What is the biggest concern with thalidomide?

Teratogenic**

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Will thalidomide cure your leprosy?

No, it only treats the SYMPTOM of leprosy, which is the fat pockets

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You’re trying to decide between rifabutin, rifampin, and ciprofloxacin for the third step of treating MAC, and your patient is 15 years old. Which one should you NOT use?

Do not use ciprofloxacin (under 18)

Fluoroquinolone

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What drug is associated with the most whoopsie pregnancies of any other drug?

Rifampin, because it decreases the effectiveness of birth control

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What are the other diseases that thalidomide has “orphan drug” status for other than the fat pockets of leprosy?

Kaposi’s sarcoma

HIV wasting syndrome

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What drugs is extreme drug resistant TB resistant to?

Isoniazid

Rifampin

Fluoroquinolones (streptomycin)

One of the injectable 2nd line drugs

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Who is it not recommended to give rifampin to?

HIV+ individuals because it messes with their HAART treatment

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What parts of the body can mycobacterium avium complex (MAC) affect?

Anywhere

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Is isoniazid in active form when you take it?

NO it is a prodrug that requires activation by the KatG enzyme ***

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What is the mechanism of action of rifampin?

Inhibits DNA dependent RNA polymerase, specifically the rpoB subunit

(Thus, DNA transcription is prevented)

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What do we use rifabutin for?

We use it instead of rifampin for HIV-Tb coinfected individuals since it is a less potent inducer of CYP3A4 and won’t have as many drug interactions

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What is the mechanism of action for isoniazid?

Inhibits Synthesis of mycolic acid

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What 2 drugs is multi drug resistant TB resistant to?

Isoniazid

Rifampin

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What is an orphan drug?

It is one that has special financial incentives for developing it since it is used for specific and rare conditions

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How do you treat mycobacterium avium complex (MAC)?

Clarithromycin or azithromycin
Ethambutol
Another oral drug (rifabutin, rifampin, or ciprofloxacin)

Need 3 drugs

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After what age should you be very careful with prescribing isoniazid for prophylactic treatment?

35 years+ due to the possibility of liver damage

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Does rifabutin turn things orange?

Yes it has orange metabolites like rifampin

What is the only tuberculostatic drug that approaches the activity of isoniazid ?

Rifampin

Is streptomycin bacteriostatic or cidal?

Cidal

What is the biggest toxicity of pyrazinamide?

Liver dysfunction*** Even more hepatotoxic than isoniazid....monitoring LFTs is imperative

How can you tell someone has active TB disease?

They are coughing and showing symptoms

Which drug for Tb has the narrowest spectrum ever

Isoniazid...only effective for TB since it inhibits mycolic acid Synthesis

What are the main toxicities of isoniazid?

Hepatitis Peripheral neuritis Hemolysis if G6PD deficient Lupus like syndrome CNS stimulation (convulsions, psychosis, insomnia etc)

Can isoniazid reach intracellular bacilli?

Yes

How is TB spread?

Droplet nuclei

If you are treating your Tb patient with isoniazid and pyrazinamide (and R and E, of course) and their liver just can’t handle it anymore, which drug should you stop, and what would be a good replacement?

Stop the pyrazinamide Replace with streptomycin

What is the mycobacterium avium complex (MAC)?

An opportunistic infection that is made up of two bacteria: M. Avium M. Intracellulare

Is isoniazid static or cidal?

Static when used alone, but cidal when in combo with rifampin

Isoniazid is a HIP drug. What does that mean?

It can cause drug induced SLE | Hydralazine, Isoniazid, Procainamide

Can pyrazinamide get into the meninges?

Yes

What are the 6 first line drugs used for TB

Isoniazid Rifampin Pyrazinamide Ethambutol Streptomycin Rifabutin

How does TB develop resistance to rifampin?

Mutated rpoB subunit

How do you treat latent TB?

Isoniazid or rifampin

How is dapsone administered?

Oral (Remember the pink and green blister packs of dapsone and rifampin?

What are the 3 drugs that are associated with causing a “lupus” like syndrome?

Hydralazine Isoniazid Procainamide (HIP drugs)

What is the mechanism of action of pyrazinamide?

It is unclear It disrupts the plasma membrane as well as energy metabolism

What is the main concern with rifampin?

It induces CYP3A4 BIG TIME MANY drug interactions

What is the most heavily regulated drug in the US?

Thalidomide

When you’re deciding whether to use clarithromycin or azithromycin for the first step to treat MAC, which would be better if your patient was on a lot of other drugs?

Azithromycin- less drug interaction

Can we give pyrazinamide by itself?

No, it must be used in combo due to high levels of resistance

What is an interesting but harmless side effect of rifampin?

Turns all secretions orange

How do you treat Mycobacterium Avium Complex (MAC)?

You need to use 3 drugs: 1. Clarithromycin or azithromycin 2. Ethambutol 3. Rifabutin, Rifampin, or ciprofloxacin

Are people with latent TB infection able to spread the disease

What is mycobacterium leprae?

Leprosy

Can we treat leprosy with one drug?

No, it is extremely unethical to do so. You are guaranteed resistance if you do that

What are the 2 components in the Mtb cell wall that are unique to that microbe?

Mycolic acid Arabinogalactan

What is the main risk of isoniazid in fast acetylators?

Hepatitis

What is the main risk of isoniazid for slow acetylators?

Peripheral neuritis | Can be given with pyridoxine to alleviate this

What is the mechanism of action of dapsone?

Similar to sulfa drugs- it interferes with PABA, and therefore folic acid synthesis

You’re trying to decide which drug you should give for the 3rd step of MAC treatment. Your patient’s germ has developed rPOB mutation. Which drug do you have to pick?

Must pick ciprofloxacin | Rifampin and rifabutin wont be effective

Does mycobacterium tuberculosis generate fast?

No, 15-20 hours, which gives them a good opportunity to form drug resistance

Is rifampin static or cidal?

Static

Does ethambutol get into the CNS/

Yes, which would be good for Tb that is causing dementia or meningitis * (Tb is not just respiratory)

How does leprosy start?

Skin patches

How do genes affect the metabolism of isoniazid/

There are fast and slow acetylators (50% of white and black people are slow Most Eskimos, native Americans, and Asians are rapid)

What is one of the most annoying side effects of dapsone and how long does it last?

Severe nasal obstruction. Improves in 3-6 months.

What are the main side effects of streptomycin?

Ototoxicity Nephrotoxicity (Its an aminoglycoside)

Can PAs prescribe thalidomide?

No, must be obtained through specially registered physicians and pharmacies

What is the mechanism of action of ethambutol?

Inhibits arabinogalactan synthesis by targeting arabinosyl transferases

What are the 2 classifications for leprosy?

PB leprosy- 1-5 patches MB leprosy- 6+ patches

What is the enzyme that is required to be in the bacillus in order for isoniazid to be active?

KatG

What is the duration of treatment for active Tb?

RIPE for 2 months Rifampin and Isoniazid for 4 months

What can you give with isoniazid to reduce the side effect of peripheral neuritis?

Pyridoxine

Is ethambutol static or cidal?

Static

What do you need to know about the 2nd line Tb agents?

Lower potency and/or more toxic

What is a common co-infection with MAC?

HIV

How do you treat leprosy (mycobacterium leprae)?

Rifampin and Dapsone | 6+ skin patches will mean you treat longer