51: Antimycobacterial Flashcards
key characteristics of mycobacteria
mycolic acid lipid-rich cell walls
acid-fast stain
intracellular in macrophages
slow-growing
describe latent TB (not a case of TB)
inactive- contained tubercel bacilli in body
TST.blood test positive but chest x ray and sputum smears negative
no symptoms and not infectious
describe active TB disease
active multiplying tubercle acilli in the body
blood test positive and chest x-ray and sputum smears abnormal
symptomatic with cough, fever and weight loss
infectious before treatment
MAC =
m. avium complex (includes m. avium, m. intracellulare and others)
cause pulmonary disease in normal ppl; acquired through respiratory droplet
disseminated disease in AIDS pts
first line treatment drugs for active TB (4)
RIPE - active TB is ripe for treatment
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
treatment for latent TB
isoniazid first-line
or isoniazid and firapentine or rifampin
MOA isoniazid
inhibits the synthesis of mycolic acid, an essential component of the mycobacterial cell wall
delivered as prodrug, which is activated by a mycobacterial catalase-peroxidase enzyme (Kat g)
activated isoniazid forms a covalent bond with at least two prtns involved in mycolic acid synthesis and impedes their function
resistance to isoniazid mechanisms
mutation in Kat G gene –> lack of pro drug activation
overexpression of the Inh A prtn –> an enzyme involved in mycolic acid synthesis
2 key adverse reactions for isoniazid
hepatitis
peripherphal neuropathy
MOA rifampin
inhibits RNA synthesis by binding to bacterial DNA-dependent RNA polymerase
resistance mechanism of rifampin
point mutations in the bacterial RNA polymerase gene
key adverse reactions of rifampin
hepatitis, red-orange color imparted to urine, feces, sweat, tears, and saliva
drug interactions for rifampin
- strong induced of cytochrome P450 which increases the elimination of many drugs and drug classes
- in HIV infected patients rifabutin should be substituted for rifampin
in HIV infected patientes ________ should be substituted for ribampin in treatment of active of latent TB
rifabutin
purpose of pyrazinambe
used in combo therapy treatment for active TB
MOA pyrazinamide
prodrug converted to active form by bacterial pyrazinamidase enzyme; antimicroial activity is dependent on acidic environment
adverse reactions pyrazinamide
hepatotoxicity
hyperuricemia - gouty
MOA ethambutol
inhibits arabinosyl transferase (involved in mycobacteria cell wall synthesis)
should you give ethambutol alone?
should always be given in combination with other drugs
adverse reactions of ethambutol
retrobulbar neuritis
hyperuricemia (less than pyrazinamide)
MOA streptomycin
interferes with bacterial prtn synthesis
adverse reactions streptomycin
ototoxic
nephrotic
combo therapy for m. avium
macrolide (clarithromycin or azithromycin)
rifampin/firamycin
ethambutol
m. avium prophylaxis in HIV pts
clarithroycin or azithromycin
two different types of leprosy (m. leprae)
lepromatous form (disfiguring skin leisons, skin test negative, large numbers of organisms)
tuberculoid form (hypopigmented plaques, milder form, skin test positive)
treatment of leprosy
dapsone
clofazimine
rifampin
therapy last for years
MOA dapsone
structural analog of para-amino-benzoic acid
- a competitive inhibitor of folic acid synthesis
MOA clofazimine
bactericidal dye with uncertain MOA
leaves a red-brown/black skin discoloration
what drugs should be started for treatment of presumptive pulmonary tb?
RIPE
alcoholism is a risk factor with traditional tb treatment why?
increased risk of developing hepatotoxicity from both isoniazid and pyrazinamide
if HIV/AID use which “r” drug?
use rifabutin, don’t use rifampin
