Respo Module - TB Drugs Flashcards
All about tb drugs
First line of agents for TB ?
Isoniazid, rifampin , ethambutol , pyrazinamide for 2 months
- isoniazid and rifampin for 4 months more
Drugs regime for px with past hx of TB or multidrug resistant tb
Isoniazid+rifampin+ethambutol+pyrazinamide (1st line of drug choice)
1st drug + aminoglycoside / injectable capreomycin / fluoroquinolone / 2nd line TB drug
MOA of isoniazid
Inhibit enzyme that synthesize mycolic acid
Name the enzymes that synthesize mycolic acid
- enoyl acyl carrier protein reductase (InhA)
- b-ketoacyl ACP synthase
What activates isoniazid?
Isoniazid is prodrug that is activated by mycobacterial catalase peroxidase (KatG)
Isoniazid is bacteriostatic in
Stationary phase
In rapidly dividing organism isoniazid is
Bacteriocidal
ROA of isoniazid
Oral administration
Adverse effects of isoniazid
Peripheral neuritis Hepatitis Mental abnormalities Optic neuritis Hypersensitivity = rash and fever Idiosyncratic hepatotoxicity
How isoniazid is inactivated before excretion
N acetylation , hydrolysis
-ve drug interactions of isoniazid
Phenytoin , carbamazepine, and benzodiazepines.
____ has broader antimicrobial activity
Rifampin
Mechanism of action of rifampin
Blocks transcription by interacting with the the beta subunit of bacterial but not human DNA dependent RNA polymerase
Rifamycin family
Rifapentin
Rifabutin
Rifampin
Rifampin is bactericidal?
True
Rifampin is also given in treatment of?
Meningitis caused by Meningococi and haemophilus influenza.
ROA of rifampin
Oral administration
Adverse effects of rifampin
- nausea , vomiting , rash
- hepatitis
- fever , chills , myalgia (when given intermittently or daily dosage of 1.2gm or greater)
- acute renal failure
- hemolytic anemia
- shock
Name of drug that is given to px infected with tb and hiv
Rifabutin
Adverse effect of rifabutin
Neutropenia Hyperpigmentation Uveitis Nausea , vomiting , rash Hepatitis
MOA of ethambutol
Ethambutol inhibits mycobacterial arabinosyl transferases,
mycobacterial arabinosyl is encoded by
embCAB operon
Arabinosyl transferases are involved in
the polymerization reaction of arabinoglycan, component of mycobacterial cell wall
roa of ethambutol ? absorption from gut ?
oral adminsitration , well absorbed from the gut.
excretion of ethambutol
by kidney , glomerual filtration and tubular secretion.
adverse effect of ethambutol
gout exacerbate
retrobulbar/ optic neuritis neuritis, resulting in loss of visual acuity and red-green color blindness
Hypersensitivity is rare.
ethambutol is contraindicated in ?
children too young to permit assessment of visual acuity and red-green color discrimination.
higher doses of ethambutol is given in ?
tuberculosis meningitis
body excretion color changes in ?
rifampin adminstration
Pyrazinamide (PZA) is ?
a relative of nicotinamide, and it is used only for treatment of tuberculosis
prodrug form / active form of PZA
pyrazinoic acid
PZA is converted into its active form by
mycobacterial pyrazinamidase
action of pyrazinoic acid
disrupts mycobacterial cell membrane metabolism and transport functions.
roa and absorption of PZA
oral , well absorbed from gut
distribution of PZA
widely distributed in body tissues, including inflamed meninges.
aminoglycoside
streptomycin
2nd line drugs for TB
Aminoglycoside, macrolide , fluoroquinolone , caperomycin , cycloserine , ethianoamide , aminosalicyic acid.
drug for leprosy
clofazimine , dapsone , rifampin
roa of streptomycin
Streptomycin sulfate is used when an injectable drug
adverse effect of streptomycin
ototoxic and nephrotoxic. Vertigo and hearing loss are the most common adverse effects and may be permanent.
MOA of ethanoamide
chemically related to isoniazid and similarly blocks the synthesis of mycolic acids.
adverse effect of ethanoamide
hepatotoxic
roa of capreomycin
intramuscularly
moa of capreomycin
peptide protein synthesis inhibitor antibiotic
capreomycin adverse effect
nephrotoxic and ototoxic. Tinnitus, deafness, and vestibular disturbances occur. The injection causes significant local pain, and sterile abscesses may develop.
moa of cycloserine
inhibits cell wall synthesis,
cycloserine adverse effects
serious toxic effects are peripheral neuropathy and central nervous system dysfunction, including depression and psychoses.
Aminosalicylic acid moa
folate synthesis antagonist that is active almost exclusively against M tuberculosis
aminosalicylic acid adverse effect
Peptic ulceration and hemorrhage may occur. Hypersensitivity reactions manifested by fever, joint pains, skin rashes, hepatosplenomegaly, hepatitis, adenopathy, and granulocytopenia often occur after 3–8 weeks of PAS therapy, making it necessary to stop administration temporarily or permanently
WHO recommendation about fluoroquinolone usage
World Health Organization recommends using a later generation fluoroquinolone such as moxifloxacin or levofloxacin.
adverse effect of linezolid
bone marrow suppression and irreversible peripheral and optic neuropathy, (prolonged courses of therapy that are necessary for treatment of tuberculosis)
linezolid is used
in combo with 2nd or 3rd line of drug , treatment of px with multi-drug resistant strain
