Flashcards in leprosy and tb drugs Deck (24):
drugs for leprosy
Rifampin (Rifadin, RimactaneR)
vs Lepromatous form
low CMI: widespread, usually symmetrical distribution of skin lesions and is characterized by anergy. Skin lesions consist of *massive numbers of macrophages* containing large numbers of bacilli.
?? are three cardinal signs of infection with M. leprae.
Skin lesions, skin anesthesia and enlarged nerves
When the host's CMI is poor, ?? develops
where the CMI response is adequate, bacillary replication is inhibited and a localized lesion develops that has a tendency to heal without treatment (??)
multi- bacillary (lepromatous) disease
indeterminate tuberculoid leprosy
tx for tuberculoid form: Paucibacillary Forms (I, TT, BT): Sulfone-sensitive strains
Dapsone: 100 mg daily for 6 months; for I and TT forms, drug is continued for 3yrs years after negative skin tests; for BT form, drug is continued for 5yrs after negative skin tests.
Rifampin: 600 mg daily for 6 months (I, TT, and BT)
tx for tuberculoid form: Paucibacillary Forms (I, TT, BT): Sulfone-resistant strains
Clofazimine: 50-100 mg daily is given in place of dapsone in the above regimen.
Multibacillary Forms (BB, BL, LL)3
Multibacillary Forms (BB, BL, LL)3
-Interferes with cell wall mycolic acid biosynthesis of mycobac (unique feature)
-mutations of inhA gene involved in mycolic acid biosynthesis renders bacresistant-->NH treatment results in selection of these resistant bac
Bacteriostatic for ??, but bactericidal for both ?? since INH penetrates cells easily.
extracellular and intracellular bacteria which are rapidly dividing
(more for slow acetylators)
Hepatitis: Major toxic effect.
tb and nontb mycobac
Bactericidal, inhibits growth of most Gram-positive as well as Gram-negative bacteria.
GI disturbances, muscle aches
Hepatitis: less frequent than INH
Important: Reddish orange color to urine, saliva, sweat and tears; there may be discoloration of soft contact lenses
Rifampin Drug interactions: Potent inducer of hepatic cytochrome P-450 enzymes and
reduces half-lives of many drugs: ??
nonnucleoside reverse-transcriptase inhibitors, protease inhibitors, anticoagulants, oral contraceptives, methadone, ketoconazole.
-meningococcal disease and meningitis due to H. influenzae,
dose-related ocular toxicity (rare, reversible); optic neuritis (decreased visual acuity, loss of color discrimination-red from green, constriction of visual fields
Hepatotoxicity, Elevations of plasma alanine and aspartate aminotransferases
Nongouty polyarthralgia (40%)
hyperuricemia (give allopurinol or probenecid)
Clofazimine [LampreneR] MOA
-binding of the agent to mycobacterial DNA and interference with bacterial growth, slowly bactericidal for M. leprae,
-Half-life is very long: 70 days. It is excreted slowly, largely unmetabolized. Only 1% in the urine.
-Pigmentation of the skin: clofazimine accumulates in cells of leprosy granuloma: red-->brown, lesions: mauve, slate gray or black
-GI tract: most serious adverse effect and develops in 50% of the patients
Inhibits the synthesis of folic acid (like sulfas) bacteriostatic, not bactericidal to M. leprae
-inhibit dihydropteroate synthetase (PABA-->DHPa-->DHF-->need for RNA synthesis?? see slide
Half-life: 10-50 hours, acetylated in the liver and excreted by the urine.
*Drug of choice for all patients infected with sulfone-sensitive M. leprae*
Sulfone syndrome: exacerbation of lepromatous leprosy.
now recommended that other antileprosy drugs (rifampin and clofazimine) be given with dapsone, why??
increasing incidence of sulfone-resistant organisms has precipitated a re-evaluation of dapsone monotherapy