Tuberculosis Rx Flashcards
Who should be given the following Tx for latent TB:
9 months of daily Isoniazid
or 2x/week using Dot*
- HIV pts.
- Children 2-11yrs
- Pregnant women w/ pyridoxine (Vit. B6) supplementation
Who should be given the following Tx for latent TB:
3 months 1x/week Isoniazid + Rifapentine
- Persons 12 and up
What to do when PT misses doses?
- Extend or re-start tx if interruptions were frequent or prolonged
- If tx interrupted for > 2 months, examine to r/o TB
- recommend and arrange for DOT as needed
Tx of active TB infection:
- Initial phase
- Continuation phase
- Daily (“RIPE”) INH, RIF, PZA, EMB for (56 doses or 8weeks)
- Daily INH and RIF for 126 doses (18 weeks) or twice weekly INH and RIF for 36 doses (18 weeks)
(I.e. discontinue PZA and EMB - Just “RI”)
Purpose of the initial phase of active TB infection tx
- Kills most of the tubercle bacilli (but some can survive)
- Prevents emergence of drug resistance
- Determines ultimate outcome of regimen
Purpose of the continuation phase of active TB infection tx
- kills remaining tubercle bacilli
- any surviving bacilli may cause TB disease at later time
The duration of TB tx depends on
- drugs used
- Drug susceptibility test results of the isolate
- PT’s response to therapy
For Active TB in HIV+ PTs:
How does the intensity of the continuation phase of TB tx change in regards to the PT’s level of immunosuppression?
Indicated by the CD4 count
- 2x/wk for CD4 > 100/uL
- Daily or 3x/wk for CD4
Isoniazid
- MOA
- Metab/Elim
- Tox
- Resistance
- Inhibits enzymes in cell-wall synthesis and nucleic acid syn. (Enoyl-acyl carrier protein reductase; dihydrofolate reductase)
- so most effective against actively dividing mycobacteria - Acetylation (May need inc. doses in Asian bc they can be fast-acetylators)
- slow acetylators at inc. risk for drug accumulation causing Lupus-like adverse affect
- inhibits CYP2C19
- Renal elimination (dose adjust in renal impairment) - Depletes Vit. B6
- Hepatitis
- Peripheral neuropathy
- Seizures
- hemolysis - Dec. metabolic activation (it’s a pro-drug) and target alterations
What must always be given with Isoniazid?
Pyridoxine (Vitamin B6)
What drugs do Isoniazid have potential to interact with?
Drugs metabolized by CYP2C19:
- several antidepressants
- Proton pump inhibitors (PPIs)
- anti-epileptic drug, Phenytoin
Rifamycins: Name them
- MOA
- Metab/Elim
- Tox
- Resistance
Rifampin, Rifapentine, and Rifabutin
- Inhibit bacterial RNA synthesis (bind and complex w/ DNA-dependent RNA pol)
- CYP-inducers! (drug-drug interactions!!)
- Watch w/ Protease inhibitors and NNRTIs (HIV)
- rifampin most potent - Red-man syndrome and Hepatotox (in predisposed)
- Target alteration and DNA repair enzymes
Pyrazinamide
- MOA
- Metab/Elim
- Tox
- Resistance
- Inhibits metabolic activity and mycolic acid synthesis
- Activated WITHIN mycobacterium
- Hepatotoxicity (dose adjust hepatic imparement); Gout; and possibly Teratogenic (NO Pregnancy)
- Altered pyrazinamind affinity by mycobacterium enzyme
Ethambutol
- MOA
- Tox
- Resistance
- Inhibits mycobacterial cell wall production (bacteriostatic)
- Inhibits arabinosyl transferase - Dose-related optic neuropathy: Change in visual acuity or red-green color blindness, blurred vision)
- Mutations in Emb locus (encodes the enzyme) and increased efflux
Drugs most commonly resisted by MDR TB?
Agents for MDR - TB?
INH and RIF
- Flouroquinolones (Levofloxacin > Moxifloxacin > Gatifloxacin) - when first lines not tolerable.
- watch for tendinitis and tendon rupture; esp in elderly, those on corticosteriods, and kidney/heart/lung transplants
