leprosy and tb drugs

Question 1

drugs for leprosy

Answer 1

Dapsone
Clofazimine (LampreneR)
Rifampin (Rifadin, RimactaneR)

Question 2

Tuberculoid form

vs Lepromatous form

Answer 2

high CMI
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.

Question 3

?? are three cardinal signs of infection with M. leprae.

Answer 3

Skin lesions, skin anesthesia and enlarged nerves

Question 4

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 (??)

Answer 4

multi- bacillary (lepromatous) disease

indeterminate tuberculoid leprosy

Question 5

tx for tuberculoid form: Paucibacillary Forms (I, TT, BT): Sulfone-sensitive strains

Answer 5

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)

Question 6

tx for tuberculoid form: Paucibacillary Forms (I, TT, BT): Sulfone-resistant strains

Answer 6

Clofazimine: 50-100 mg daily is given in place of dapsone in the above regimen.

Question 7

Multibacillary Forms (BB, BL, LL)3

Answer 7

?

Question 8

Multibacillary Forms (BB, BL, LL)3

Answer 8

?

Question 9

INH: MOA

resistance??

Answer 9

• 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

Question 10

Bacteriostatic for ??, but bactericidal for both ?? since INH penetrates cells easily.

Answer 10

“resting” bacilli

extracellular and intracellular bacteria which are rapidly dividing

Question 11

INH SEs

Answer 11

(more for slow acetylators)
Peripheral neuropathy
Hepatitis: Major toxic effect.

Question 12

INH uses

Answer 12

tb and nontb mycobac

more

Question 13

rifampin MOA

Answer 13

Bactericidal, inhibits growth of most Gram-positive as well as Gram-negative bacteria.

Question 14

rifampin SEs

Answer 14

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

Question 15

Rifampin Drug interactions: Potent inducer of hepatic cytochrome P-450 enzymes and
reduces half-lives of many drugs: ??

Answer 15

nonnucleoside reverse-transcriptase inhibitors, protease inhibitors, anticoagulants, oral contraceptives, methadone, ketoconazole.

Question 16

rifampin uses

Answer 16

• tb
• meningococcal disease and meningitis due to H. influenzae,
• leprosy

Question 17

Ethambutol SEs

Answer 17

dose-related ocular toxicity (rare, reversible); optic neuritis (decreased visual acuity, loss of color discrimination-red from green, constriction of visual fields
-discontinue immediately

Question 18

Pyrazinamide SEs

Answer 18

Hepatotoxicity, Elevations of plasma alanine and aspartate aminotransferases

Nongouty polyarthralgia (40%)
hyperuricemia (give allopurinol or probenecid)

Question 19

Clofazimine [LampreneR] MOA

half-life??

Answer 19

• 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.

Question 20

Clofazimine SEs

Answer 20

• 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

Question 21

Dapsone MOA

Answer 21

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

Question 22

Dapsone SEs

Answer 22

hemolytic anemia
Methemoglobinemia
Sulfone syndrome: exacerbation of lepromatous leprosy.

Question 23

now recommended that other antileprosy drugs (rifampin and clofazimine) be given with dapsone, why??

Answer 23

increasing incidence of sulfone-resistant organisms has precipitated a re-evaluation of dapsone monotherapy

Question 24

Dapsone, other use

Answer 24

acne