Antimycobacterials Flashcards
What kind of cell does TB usually live in?
Macrophages
What is the treatment of choice for erythema nodosum leprosum?
Thalidomide
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
What is the mechanism of action of streptomycin?
Inhibits 30s ribosome (its an aminoglycoside)
What kinds of testing must you do on your patient before and during isoniazoid treatment?
Liver Function Tests
What is erythema nodosum leprosum?
Fat pockets that are the symptom of leprosy
What is the spectrum of ethambutol?
VERY narrow….it affects arabinogalactan, which is only in mycobacterium Tb
What is another use for rifampin?
Leprosy
What is the biggest concern with thalidomide?
Teratogenic**
Will thalidomide cure your leprosy?
No, it only treats the SYMPTOM of leprosy, which is the fat pockets
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
What drug is associated with the most whoopsie pregnancies of any other drug?
Rifampin, because it decreases the effectiveness of birth control
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
What drugs is extreme drug resistant TB resistant to?
Isoniazid
Rifampin
Fluoroquinolones (streptomycin)
One of the injectable 2nd line drugs
Who is it not recommended to give rifampin to?
HIV+ individuals because it messes with their HAART treatment
What parts of the body can mycobacterium avium complex (MAC) affect?
Anywhere
Is isoniazid in active form when you take it?
NO it is a prodrug that requires activation by the KatG enzyme ***
What is the mechanism of action of rifampin?
Inhibits DNA dependent RNA polymerase, specifically the rpoB subunit
(Thus, DNA transcription is prevented)
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
What is the mechanism of action for isoniazid?
Inhibits Synthesis of mycolic acid
What 2 drugs is multi drug resistant TB resistant to?
Isoniazid
Rifampin
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
How do you treat mycobacterium avium complex (MAC)?
- Clarithromycin or azithromycin
- Ethambutol
- Another oral drug (rifabutin, rifampin, or ciprofloxacin)
Need 3 drugs
After what age should you be very careful with prescribing isoniazid for prophylactic treatment?
35 years+ due to the possibility of liver damage
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
- Ethambutol
- Rifabutin, Rifampin, or ciprofloxacin
Are people with latent TB infection able to spread the disease
No
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
