Drugs Used to Treat TB Flashcards
What is a major risk factor for acquiring MDR TB vs. just a regular TB infection?
• what is MDR TB resistant to?
• What is XDR TB resistant to?
• TB contracted outside the US is more likely to be a MDR strain of TB.
MDR TB: resistant to isoniazid and rifampin
XDR TB: resistant to isoniazid, rifampin + FLUROQUINOLONES and more than 1 of 3 injectable 2nd line drugs
What makes MTB inherently resistant to many antibiotics as it stands alone?
• what drugs are especially equipped for penetrating this wall?
MA-AG-PG cell wall (mycolic acid (outermost) - arabinoglycan - peptidoglycan (innermost)
• IN particular Mycolic acid prevents the the entry of most non-lipophilic drugs
Rifampin and Fluroquinolones are lipophilic and capable of penetrating the cell wall
If you biopsied the center of a granuloma would you expect to find TB?
NO - TB is an aerobic organism so it stays in living tissue (MACROPHAGES) where it can get O2
This is also why it hangs out in the apex of the lungs
What are some methods TB uses to become XDR.
- Efflux pumps
- Target Modifications
- Enzyme Decoys
What patients may benefit from close monitoring of taking TB medications?
- Patients who have previously failed to complete anti-TB regimen or other drug regimens
- Physically, Mentally, or emotionally challenged people
- Patients abusing drugs, EtOH, or other addictive substances
- Ppl who don’t understand or have different cultural beliefs
Its important that most patients take TB medication under DOT (directly observed therapy) but who is it VERY, VERY, important in?
• Children, HIV, immunosuppressed, and those with Drug resistant infections
Are carriers of Latent TB infections able to spread it to to others?
• what does the CXR look like in latent carriers?
NO - CXR in a latent carrier of TB looks completely normal
Before starting anyone on a Infliximab, etanercept, aldalimumab, certolizumab, or golimumab what should you do?
Screen patients for TB before starting any kind of TNF-alpha blocker - if you don’t there is a high risk of Reactivation of latent TB
What patients do you need to excercise precaution with when administering Isoniazid to for TB?
• PREGNANT WOMEN: need B6 supplements - (lack of B6 supplementation in patients taking isoniazide could lead to anemia, glossitis, dermititis, or neuropathy )
Who CANNOT recieve Rifapentine?
People who can’t take Rifapentine:
• under 2
• on concurrant anti-retrovirals (problem with AIDS pts)
• Not on for women who are pregnant or expect to become pregnant while on the 3 mo. regimin)
What therapy is given for latent TB?
Isoniazid for 6mo. or Isoniazid + Rifapentine for 3 mo.
• note: there are many potential complications for rifapentine
What should you do the the case that:
• your patient missed a lot of TB treatments
• treatment was interrupted for more than 2 months
Lot of Missed Tx:
• may need to restart regimen
Patient w/ 2 or mo. of interrupted therapy:
• re-examine patient for the emergence of TB, restart therapy
How do you manage TB infections in a patient with HIV?
• what determines the dose and frequency of tx?
2 mo.
• RIPE but use RIFAMYCIN not rifapentine
4 mo.
• Rifamycin + INH
Dosing and frequency is determined by the CD4+ count
What is the MOA of Isoniazide?
• how it is excreted?
MOA:
• Isoniazid also diffuses into mycoplasma where it gets ACTIVATED by KatG (via oxidation and peroxidation) to the nicotinoyl radical
• Radical binds to NAD+ or NADP+ to produce adducts that inhibit: 1) enoyl-acyl carrier protein reductase (InhA) needed for cell-wall formation and 2) DHFR needed for nucleic acid synthesis
Elimination:
• NAT2 metabolizes Isoniazid to N-acteyl Isoniazid to become inactive and RENALLY excreted
Based on its MOA, what can you assume are some of the Mechanisms of resistance against Isoniazid?
KatG mutation = Prevents activation of the drug to a radical
Alteration of: enoyl-acyl carrier protein reductase InhA and DHFR in the TB also can confer resistance
