TB Tx: Buzz Words and Basics Flashcards
Anti-TB drug cocktail?
Isoniazid
Rifampin
Pyrazinamide
Ethambutol
(Rifabutin and Rifapentine are alternatives to Rifampin)
What is a common second-line anti-TB drug?
Streptomycin
Where is INH metabolized?
Liver, via acetylation - be aware of fast acetylators, who will have lower concentration of INH in the plasma and a shorter half-life
What is a consideration when giving INH to a patient on dialysis?
Give it after dialysis, because it will be removed by dialysis
INH adverse effects?
Hepatotoxicity
(bigger risk for pregnant/recent post-partum, EtOH, geriatric, liver dz patients)
Increases AST/ALT
Neuropathy: supplement with B6/pyridoxine to avoid optic neuritis/peripheral neuropathy
Orange secretions are associated with which drug?
Rifampin
Adverse effects/special considerations with rifampin?
**Potent CYP450 inducer!
Orange secretions
Hepatotoxicity (not as bad as INH)
Flu-like syndromes also possible + rash, fever, n/v; mitigated by intermittent dosing.
What drug would warfarin be impacted by, and how?
Rifampin: it is a CYP450 inducer, meaning that it increases the rate of elimination of drugs like warfarin.
INR would decrease (clots more likely) when rate of elimination of warfarin increases during rifampin use.
It goes DOWN, Jules.
Patient has Mycobacterium avium complex. Which drug in the cocktail would you switch?
Rifampin –> Rifabutin
Adverse effects of ethambutol?
Possible optic neuritis/red-green color blindness (avoid in kids);
hyperurecemia –> gout
Adverse effects associated with pyrazinamide
Hepatotoxicity; hyperurecemia –> gout
Pharmacokinetic basics of streptomycin
Given IM (not PO)
Mostly renal elimination (maybe better in pt with reduced hepatic function)
Adverse effects/considerations with streptomycin?
Nephrotoxicity
Ototoxicity
Hypersensitivity
Congenital deafness (don’t use in pregnancy)
Monotherapy = resistance
Preferred LTBI Regimens
Rifampin daily x 4 months
Easiest, caution for drug interactions
Only for HIV neg
2 alternative regimens:
Rifapentine + Isoniazid once/week for 3 months with required DOT
Better completion, but higher cost; ok for HIV+
OR
Rifampin + Isoniazid daily for 3 months
Caution for AE/drug interactions
TB Disease Regimen
All 4 drugs (Rif, Inh, Pza, Emb) for 8 weeks (induction period)
Then
Continue just Rif and Inh for 18 weeks, if bacteria is found to be susceptible
A patient with afib is stable on warfarin and starts LBTI therapy. What needs to be monitored and why?
Patient’s INR may decrease and be more prone to clots due to the rifampin’s effect as a CYP inducer.
Which drug can cause decreased visual acuity and color discrimination?
Ethambutol
List 4 factors that could increase risk for INH-induced hepatotoxicity
Alcoholic hepatitis
Concurrent rifampin therapy
Age > 65 YO
Pregnancy/post-partum
Which drug is associated with increase serum uric acid?
Ethambutol
Which drug is associated with peripheral neuropathy?
Isoniazid
Which drug is associated with ototoxicity?
Rifampin and streptomycin
Which drug is activated by KatG enzymes in the bacillus?
Isoniazid
What should be supplemented when a patient begins 4-drug TB treatment?
Pyridoxine/B6 (to prevent peripheral neuropathy due to INH)
Which two TB drugs affect cell wall synthesis, and how do they differ?
Isoniazid inhibits mycolic acid synthesis
Ethambutol inhibits arabinogalactan synthesis
What is the MOA of rifampin?
Targets RNA polymerase, inhibits transcription
What is the MOA of pryrazinamide?
Targets S1 of 30S ribosomal subunit; works via multiple mechanisms (we’re not totally sure how)
What is the MOA and class of streptomycin?
Aminoglycoside: Inhibits protein synthesis
Some of the second/third line agents for TB end in -floxacin; what class are they and what is their MOA?
Quinolones: inhibit DNA supercoiling
