Antimycobacterials Flashcards
Isoniazid is less effective in
Atypical mycobacteria
Isoniazid
If used as a single drug
10-20% prevalence
Isoniazid
As a single agent in cases of
Recent converters
Immunocompromised individuals
Close contacts
Abnormal chest x ray but activity has been R/O
Complex semisynthetic derivative of Rifampicin
Rifampin
Rifampin
Active against
Gm - and + cocci
Some enteric bacteria
Chlamydia
Rifampin
Cross resistance with
Rifabutin
Rifampin
Clinical use
Mycobacterial infection - + INH, ethambutol x 6month
Atypical mycobacteria - 600 mgd or 2x weekly x 6 months
Leprosy- + sulfone
Rifampin
Other indication
Meningococcal carriage
H. Influenza type B contact
Staph
Pneumococci (menigitis)
Synthetic, water soluble, heat stable compound
Ethambutol
Ethambutol
Most common adverse effect
Loss of visual acuity and red green color
Ethambutol
CI
Very young because visual acuity assessment is difficult
A relative of nicotinamide, stable, inexpensive
Pyrazinamide
Pyrazinamide
Inhibits
Intracellular organism
Resistant to some non tuberculous species
Streptomycin
Streptomycin
Extracellular tubercle bacilli;
Inflamed meninges
Streptomycin
Clinical use
Severe, life threatening forms of TB
Drug resistance
Streptomycin
Adverse
Oto toxicity
Nephrotoxicity
Treatment of TB: guidelines for national programmes 3rd edition. WHO Geneva June 2004
H- isoniazid R- Rifampicin S- streptomycin Km- kanamycin Q- quinolone (ciprofloxacin or ofloxaxin) Z- pyrazinamide E- ethambutol Cs- cycloserine Et- etionamide
DOTS stands for?
Directly Observed Treatment Short course
Five elements of DOTS
Political commitment Quality sputum microscopy for diagnosis Regular supply of anti TB drugs Standardized recording and reporting of TB data Supervised treatment
TB and pregnancy
INH, Rifampicn, ethambutol vit B6
Risk of teratogenicity
PZA
Infants should be given 3 mos.
INH prophylaxis
Related to INH, poorly soluble in water
Ethionamide
Ethionamide
MOA
Blocks mycolic acid synthesis
Ethionamide
Adverse reaction
Hepatotoxic
Neurotoxicity
Ethionamide
Resistance
When used as single agent
Capreomycin
MOA
Peptide protein synthesis inhibitor from streptomyces capreolus
Capreomycin
Used for multi drug resistant cases
Streptomycin
Amikacin
Capreomycin
Resistance
rrs mutation
Capreomycin
Adverse effect
Nephrotoxic
Ototoxic
Cycloserine
MOA
Inhibitor of cell wall synthesis
Cycloserine
Adverse effect
Peripheral neurophaty CNS dysfunction (give pyridoxine)
Aminosalycylic acid
MOA
Folate synthesis antagonist
Aminosalycylic acid
Structure
Similar to PABA and sulfonamides
Aminosalycylic acid
Widely distributed in tissues and body fluids except in
CSF
Excreted in urine
Aminosalycylic acid
Adverse effects
Anorexia Nausea LBM Epigastric pain Peptic ulceration Hemorrhage Hypersensitivity reaction
Kanamycin and Amikacin
MOA
Inhibits 30s ribosomal subunit
Kanamycin and Amikacin
For streptomycin resistant cases,
Multi drug resistant TB
Atypical mycobacterium
Ciprofloxacin and levofloxacin
MOA
Inhibits gyrase mediated DNA- supercoiling
Ciprofloxacin and levofloxacin
M. TB
Levo> ciprofloxacin
Ciprofloxacin and levofloxacin
Atypical myco
Levo
Ciprofloxacin and levofloxacin
Prophylaxis
Fluoroquinolone + PZA
Ciprofloxacin and levofloxacin
Resistance
Mutations in gyrase A subunit
Derived from rifamycin, related to rifampin
Rifabutin
Rifabutin
Uses
TB, Avium, foruitum
Aids with cd4 count of
Rifabutin
Resistance
rpo mutation
Rifabutin
Less potent inducer
For HIV infected patients receiving other meds
Analog of rifampin; against M. TB , M Avium
Rifapentine
Rifapentine
MOA
Bacterial RNA polymerase inhibitor
Rifapentine
Potent inducer of
Cytochrome p450
Rifapentine
Dose
600 mg once or 2x weekly
Last resort of multi drug resistant TB
Clofazimine
Effective against leprosy
Clofazimine
Clofazimine
MOA
Unknown
Involved in DNA binding
Clofazimine
AE
Skin dis colorization
GIT intolerance
Inhibits protein synthesis (50S)
Linezolid (oxazolidinones)
Linezolid (oxazolidinones)
AE
Hematologic (thrombocytopenia, neutropenia)
TB diagnostic category
Table memorize
Not communicable from person to person
Disease produced are less severe than TB
Atypical Mycobacteria
Disseminated disease in late stages of AIDS
MAC
MAC
1st line treatment
Azithromycin 500mg
Clarithromycin 500 mg + ethambutol 15mg
Clofazimine/ciprofloxacin 750mg
Amikacin
MAC
2nd line treatment
Rifabutin 300 Rifampicin Ethionamide Cycloserine Imipenem
MAC
Prophylaxis in aids PT
Rifabutin 300 mg OD
Mycobacterium marinarum
1st line tx
Rifampicin + ethambutol
Mycobacterium marinarum
2nd line treatment
Clarithromycin Amikacin Kanamycin Minocycline Doxycycline
Similar to TB but milder
Mycobacterium kansasii
Mycobacterium kansasii
1st line treatment
INH + Rifampicin + ethambutol
Mycobacterium kansasii
2nd line
Ethionamide Cycloserine Clarithromycin Amikacin Streptomycin
Cervical lymphadenitis
Mycobacterium fortuitum
Tx, surgical excision
Chronic lung disease and skin soft tissue infection
Mycobacterium fortuitum
Mycobacterium fortuitum
1st line
Amikacin+ doxycycline
Mycobacterium fortuitum
2nd line
Cefoxitin,
Rifampicin
Leprosy
Skin and nerve
Cell mediated immunity
Leprosy mode of transmission
Nasal secretions
Dx leprosy
Slit skin smears
Skin macules with clear centers and well defined margins, anesthetic,
Tuberculoid leprosy
Impaired cell immunity,
Atrophy of skin
Muscles amputations
Spontaneous ulceration
Lepromatous
Major chemotherapeutic agents against M. Leprae
Dapsone (DDS) Rifampicin Clofazimine Ofloxacin Minocycline
Other chemotherapeutic agents for leprosy
Levofloxacin
Sparfloxacin
Clarithromycin
Dapsone
MOA
Inhibits folate synthesis
Mycobacterium fortuitum
Adverse effects
Hemolysis
GIT intolerance
Erythema nodosum leprosum
Exacerbation of lepromatous leprosy
Jarisch-herxheimer reaction
Clofazimine (lamprene)
MOA
Inhibit the template function of DNA
Clofazimine
SE
Discoloration of the skin
Eosinophilic enteritis
Miscellaneous agents for leprosy
Thalidomide - tx of erythema nodosum
Ethionamide - substitute for clofazimine
The most active drug for the treatment of TB
Isoniazid
