TB drugs- Allman Flashcards
define multidrug-resistant (MDR) TB
- resistant to at lead INH AND RIF
what are MDR patients at high risk for
-treatment failure and further acquired drug resistance
what happens to patients with just strain resistant to RIFAMPIN alone
- better prognosis
- increase risk for treatment failure
What is extensive drug Resistant (XDR) TB
- MDR TB plus resistance to FQN
- AND resistant to at least one other of the 3 injectable drugs
- amikacin
- kanamycin
- capreomycin
what defines therapeutic failure
positive sputum coherent scattering after 4 months of compliant therapy
what is the dosing guideline for TB drugs
- daily dosing
- twice or thrice weekly dosing
- Directly observed therapy
MOA for Rifampin
inhibits DNA-dependent RNA polymerase
- suppression of initiation of chain formation in RNA synthesis
Bactericidal: kills slow-growing mycobacteria present within macrophages and in caseating granulomas
where is Rifampin distributed
CNS
tuberculosis abscesses
intracellular sites
How is Rifampin metabolized
deacetylation
- autoinductin of metabolism occurs
- Rifampin Revs up Liver
3 major adverse effects of Rifampin
- transient elevation in serum transaminases
- hepatotoxicity
- orange discoloration ( sweat, tears, urine)
- Rifampin revs up and red
Drug interaction of Rifampin
- increase in cytochrome P-459
- increases metabolism of
- warfarin
- narcotics
- steroids ( oral contraceptives)
place in therapy: Rifampin
- treats active TB
- 2nd line agent for preventative therapy
MOA for Isoniazid ( INH)
inhibits synthesis of mycolic acid
metabolism of Isoniazid
acetylation
Rate of acetylation of Isoniazid depend son what
genes: can be slow or rapid acetylator
Adverse effects of Isoniazid
- transient elevation in serum transaminases
- hepatotoxicity
- Neurotoxicity
who is neurotoxicity seen in with Isoniazid, treatment?
- alcoholics, homeless
- Pyridoxine ( B6)
MOA for Pyrazinamide
- not well known
- toward dormant organism
Adverse effects of Pyrazinamide
Hepatotoxicity
hyperuricemia : decreased renal excretion of uric acid, bad for gout patients
MOA for Ethambutol
not well known
bacteriostatic
how is Ethambutol excreted
urine
Adverse effects of Ethambutol
optic neuritis ( retrobulbar neuritis) -decrease visual acuity and red-green color blindess
Ethambutol should be used with caution in what patient group
children
MOA for Streptomycin
Aminoglycoside antibiotic
- inhibit protein synthesis
how is streptomycin absorbed and administered
poorly absorbed in GI tract
- given IM or IV
Adverse effects of Streptomcin
nephrotoxicity
impairment of 8th cranial nerve function
which is better ethambutol or streptomycin
ethambutol
when can you not give rifabutin
- unacceptable interactions with Rifampin
- or intolerance to Rifampin
Adverse reactions for Rifabutin
rash
GI
NEUTROPENIA
who can receive Rifapentine
HIV negative
- non-cavitary, drug susceptible pulmonary tuberculosis
what is the most widely used antilieprosy agent
Clofazaime
MOA of Clofazaomine
binds preferentially to mycobacterial DNA causing inhibition of transcription
Adverse effects of Clofazamine
- GI
- severe and life threatening abdominal pain and organ damage caused by crystal deposition
- discoloration of skin and eyes
how long is general treatment for TB
6 months
how long is treatment for osteo/miliary/meningitis
12-24 months
if a TB patient has renal failure what should you avoid
Streptomycin
Kanamycin
Capreomycin
TB children should avoid what medicine
Ethambutol
when is suspected treatment failure seen
- lack of clinical progression 6-8 wks into therapy
- add 2 or more new TB agents
treatment for Mycobacterium leprae should include
Dapsone
Rifampin
Clofazimine
DR. C
MOA for Dapsone
competitive inhibitor of folic acid synthesis
what are 2 major categories for Leprosy
- lepromatous - disseminated
2. Tuberculoid - localized
How is leprosy transmitted
prolonged contact
how long is drug course of leprosy
2-5 years
what are symptoms for MAC
fever
night sweats
weight loss
anemia
Who does MAC usually occur in
HIV less than 100 CD4
when is primary prophylaxis recommended for HIV MAC
CD4 less than 50
How do non-HIV patients present with MAC
in lungs
chronic productive cough
prophylaxis regimen for MAC
Clarithromycin
Azithromycin
Alternative Rifabutin if above2 not tolerated
Treatment regimen for MAC
at least 2 agents
- Clarithromycin or Azithromycin plus Ethambutol
- consider adding one of the following: Clofazamine, Rifampin, Rifabutin or Cipro
how long is RIPE regiment
6 months total
- 2 months RIPE
- 4 months RI
how long is RIP regiment
6 months total
- 2 months RIPS
- 4 months RI
which drug is more active against MAC
Clarithromycin
