Block V- Pulm TB & Mycobacterium Treatment Flashcards
Why use multi-drug therapy with active TB?
- enhances rates of response/cure
- reduces emergence of resistance
What are methods of increasing adherence/Rx completion?
- shortest possible course of therapy
- DOT
Why do you need an adequate duration of TB therapy?
- increase cure rate
- reduce relapse
How is Isoniazid HCL used clinically?
- first line drug for active pulmonary TB
- used in combo with at least 2 other active drugs, except for when treating LTBI
What is the MOA of INH?
- pro drug that is activated by catalase peroxidase
- targets inhA gene products (cell wall my colic acid)
what is the gene which encodes catalase peroxidase?
TB katG gene
How dose INH resistance develop?
- mutations in the katG gene
- mtuations in the inha gene
does INH reach the CNS?
you bet
What is INH toxicity?
- Hepatotoxic: inc w/ pregnancy
- Neurotoxic
- Hypersensitivity Rxn
How can you reduce neurotoxicity in INH therapy?
-give them Vitamin B6 (pyridoxine)
What are some notable INH drug interactions?
- rifampin (hepatitis)
- Dilantin (reduced clearance)
- intraconazole and levadopa (dec. levels)
What are the clinical uses of Rifampin?
- first line for TB (in combo , xc for LTBI)
- Gram + like S. aureus in combo
- N. meningitidis (alone)
Why can’t you use Rifampin alone?
-rapid development of resistance
what is the MOA of Rifampin?
- inhibits DNA dependent RNA polymerase
- endocded by rpoB gene
How does resistance to Rifampin develop?
-mutations in the rpoB gene
is Rifampin bactericidal or static?
cidal all the way
Does Rifampin get to the CNS?
it does
what are some adverse effects of Rifampin?
- Hepatotoxicity
- Red discoloration of body fluids
- ARF, interstitial nephritis
- influenza syndrome
- thrombocytopenia
- cholestatic jaundice
What are drug interactions in Rifampin?
- too many to count (over 100!)
- coumadin, estrogen, anticonvulsants, antiretrovral drugs, etc.
What is the clinical use of Ethambutol?
- first line TB therapy
- helper drug to inhibit resistance to other drugs
What is the MOA of Ethambutol?
- inhibits TB arabinosyl transferase encoded by the embB gene
- effects wall synthesis
is Ethambutol tidal or static?
static
Does Ethambutol reach the CNS
no
What are adverse effects of Ethambutol?
- Optic neuritis CAN MAKE YOU BLIND
- Peripheral neuropathy - less common
What is the clinical use of Pyrazinamide?
- first line TB drug for the FIRST TWO MONTHS OF THERAPY
- always used in combo
what is the MOA of Pyrazinamide?
-prodrug activated by TB pyrazinamidase encoded by pncA gene
How dose PZA resistance occur?
-mutations of the pncA gene
is PZA cidal or static?
cidal
Does PZA reach the CNS?
yes!
What are adverse effects of PZA?
Hepatitis
rash
GI issues
inc. serum uric acid (but no gout)
What are clinical uses of Streptomycin?
-second line TB drug
What is the MOA of Streptomycin?
-inhibits protein synthesis by binding to ribosome
how dose resistance to Streptomycin occur?
- mutation of ribosomal binding site
- not cross resistant to amikacin, kanamycin, capreomycin
Does Streptomycin enter the CNS?
only in the presence of inflamed meninges
What are adverse effects of Streptomycin?
- Ototoxicity
- Nephrotoxicity
What is Primary Resistance?
infection by a source case with drug resistant TB
What is secondary resistance?
From ineffective therapy (poor treatment design or adherence)
- too few drugs to prevent emergence of resistance
- suboptinal drug dosing or absorption
How do you calculate the risk of evolution of resistance to two drugs?
the product of the risk of the development of resistance to each drug – INH®~10-8 + Rifampin®~10-9 INH/Rifampin = 10-8 x 10-9 = 10-17
Define MDR-TB
resistance to both INH and Rifampin
-more common with HIV infected patients
What will it mean for therapy if Rifampin resistance develops?
you will not be able to use short course (6month) TB therapy and will need therapy for 18-24 months
How effective is 6 month TB treatment?
95% cure rate
What is the 4 drug regimen for 6 month TB therapy?
RIPE (initial)
-rifampin, INH, PZA, and Ethambutol
RI (continual)
When can you use intermittent therapy plans?
only with DOT
When can 6 month therapy be used?
- Adherence is high
- Sputum cultures convert by 2 months
- no major cavitary lung disease
- no rifampin resistance
How do you treat a latent TB infection?
- INH mono therapy for 9 mo
- Rifampin for 4 mo
- INH + Rifampin for 3 mo (DOT)
Which drugs are only active against TB?
INH
PZA
which drugs are active against TB and NTM?
Rifampin
Ethambutol
fluroquinolones
aminoglycosides
Which drugs are only active against NTM?
Clarithromyocin
Azithromyocin
How does the treatment of leprosy compare to the treatment of TB?
it’s very different
How do you treat Paucibacillary leprosy?
Rifampin and dapson daily for 12 mo
How do you treat multibacillary leprosy?
rifampin and dapson and clofazimine daily for 24 months
