Exam 3: Antituberculotics Flashcards
How is TB spread?
Droplet nuclei, expelled when a person with infectious TB sneezes, speaks, sings, or coughs
What drugs are multi drug resistance TB resistant to?
Isoniazid and rifampin
What drugs are extreme drug resistant TB resistant to?
Isoniazid, rifampin, any fluoroquinolone, and injectable second line drugs (Kanamycin, capreomycin, and amikacin)
How is active TB treated?
Isoniazid, rifampin, ethambutol, and pyrazinamide (HRZE)
***All 4 for the first 2 months, then only isoniazid and rifampin for 4 months
Why is TB treated with 4 different drugs?
Helps reduce Multiple drug resistant bacteria and significantly reduces transmission rates to other people with the first two months of treatment
What are the 3 ways to treat latent TB?
1) isoniazid + rifapentine 1 a week for 12 weeks
2) Rifampin daily for 4 months
3) Isoniazid either daily or twice weekly (76-270 doses)
What is the MOA of isoniazid?
Inhibits synthesis of mycolic acid- a prodrug that is activated by KatG
When is isoniazid used?
- Monotherapy for latent TB
- Used in combination for active TB
What is the route of administration of Isoniazid?
Oral
How is isoniazid metabolized?
Metabolized by acetylation in the liver inactivates the drug.
Excretion is though urine.
Metabolic rate of INH is dependent on genetic makeup (there are fast and slow acetylators)
What are the toxicities of isoniazid?
-Hepatitis (fast acetylators) peripheral neuritis (in slow acetylators), hemolysis, drug induced lupus, and CNS stimulation (Convulsions, insomnia, vertigo)
What is the MOA of Rifampin?
Inhibits DNA dependent RNA polymerase
-Taken orally
Aside from TB, what else is Rifampin effective against?
Leprosy, most G+ cocci, and some G- microbes
How is rifampin used in the treatment of TB?
- Monotherapy for latent TB
- Combination therapy for active TB
What are the toxicities associated with Rifampin?
- Hepatic enzyme induction: potent inducer of P450, drug interactions
- Harmless orange color to urine, sweat, and tears
- Decreased effectiveness of birth control
Who is rifampin not recommended for?
HIV-treated individuals due to drug interactions
What is the MOA of Ethambutol?
Is it static or cidal?
Inhibits arabinosyl transferases involved in the synthesis of arabinogalactan.
-Bacteriostatic
Out of the 4 drugs used in combination therapy to treat active TB, which ones have CNS penetration?
Ethambutol and Pyrazinamide
What are the toxicities associated with ethambutol?
-Decrease in visual acuity and loss of green-red perception.
Who is ethambutol not recommended for, why?
Children below the age 13 due to effect on vision
When is pyrazinamide most active?
At an acidic pH
-greatest activity against dormant organisms
What are the toxicities associated with pyrazinamide?
Hepatic dysfunction, hyperuricemia –> gout, myalgias, GI upset, and photosensitivity
Why is pyrazinamide a critical first line drug for TB?
It is responsible for reducing therapy to the current standard of 6 months (previously 9-12 months)
What is the MOA of streptomycin? Static or cidal?
Protein synthesis inhibitor (30s)
Bactericidal
What are the toxicities associated with streptomycin?
Ototoxicity and nephrotoxicity
What is the MOA of rifabutin?
Inhibits DNA dependent RNA polymerase
What is the DOC for HIV-TB coinfected individuals and why?
Rifabutin (instead of rifampin) because it is a less potent inducer of P450 enzymes and has less drug interactions
What is the MOA of Rifapentine?
Inhibits DNA dependent RNA polymerase
What side effect is seen in rifampin, rifabutin, and rifapentine?
They cause orange colored metabolites
What is the preferred therapy for latent TB, even in HIV+ patients?
Rifapentine and isoniazid
What is the treatment for Mycobacterium Avium Complex?
1) Either clarithromycin OR azithromycin
2) Include ethambutol
3) Add third oral drug (rifabutin, rifampin, or ciprofloxacin)
12 month treatment
What happens if you treat Mycobacterium leprae with only one antileprosy drug?
It will ALWAYS develop resistance. This is considered an unethical practice!
What is the treatment for PB leprosy?
Rifampin and dapsone for 6 months
What is the treatment for MB leprosy?
Rifampin and dapsone for 6-12 months
What kind of leprosy has 1-5 patches?
PB leprosy
What kind of leprosy has more than 5 patches?
MB leprosy
What is the MOA of Dapsone?
Similar to sulfas (PABA antagonist), inhibits folate synthesis
** why sulfa drugs are not effective against leprosy is not known.
What are the toxicities associated with Dapsone?
- Nasal obstruction that improves after 3-6 months
- Dose related hemolysis
- Peripheral neuritis
- Methemoglobinemia, leukopenia, allergic dermatitis
What is the DOC for moderate to severe Erythema Nodosum Leprosum (ENL)?
Thalidomide
What is thalidomide used to treat?
ENL, lepromatous leprosy, treatment of mycobacterium infections, and primary brain malignancies
What is the main adverse effect of thalidomide?
Teratogenic, should not be used at any time during pregnancy
