Antimycobacterial Drugs

Front 1

What staining method is used to view mycobacterium TB?

Back 1

Acid fast Ziehl Neelsen Stain- shows up as red bacilli

Front 2

Isoniazid (INH)- Use, MOA

Back 2

Use- First line treatment for TB
MOA- bioactivated by katG catalse and then will inhibit enzymes for mycolic acid synthesis (found in cell wall)

Front 3

Isoniazid - PK, resistance

Back 3

PK- MAIN PT-- intracellularly distrib, Acetylation varies in diff populations
Resistance: due to deletion of katG catalase

Front 4

Isoniazid (INH)- PK, tox, contraindication

Back 4

- Tox- hepatitis, neuropathy, B6 deficiency
- PK-liver metabolization varies by ethnicity.
- Contraindication- inhibits metabolism of phenytoin by P450 liver enzymes and potentiates the symptoms of ataxia ass. with phenytoin. Also, B6 (pyrodoxine) should be given prophylactically to prevent neuropathy

Front 5

Rifampin (RIF)- Use, MOA

Back 5

Use: First line treatment for TB
MOA: Blcoks transcription by inhibiting bacterial DNA dependant RNA polymerase by binding to beta subunit and inhibits RNA synthesis. Is bacteriacidal

Front 7

Rifampin- Toxicity, Use

Back 7

- abdom discomfort, skin eruptions, hepatitis. INCREASES ELIMINATION of other drugs (so must observe drug levels) i.e. oral birth control. Urine and tear drops have reddish color. HIV pts should be given Rifabutin b/c it does not increase metabolism of protease inhibitors
Use: TB, MB and PB leprosy

Front 8

Pyrazinamide(PZA)- Use, MOA

Back 8

Use: First line TB
MOA: Pnca enzyme in bacteria converts to active form which is pyrazinoic acid (pyrazinoic acid will accumulate in bacterial cells, causing death). Is active at acidic pH (imp b/c TB residing in macrophages in the lysosomes). Bacteriacidal.

Front 9

Pyrazinamide-Tox, Use

Back 9

Tox- hepatitis, hyperuricemia, gout, arthralgia, fever, and skin rash. Thus must monitor SGOT and uric acid levels
Use: First line treatment of TB

Front 10

Ethambutol- Use, MOA

Back 10

Use: TB - first line treatment, may also treat TB meningitis
MOA: Inhibits arabinosyl transferase* involved in bacterial wall synthesis. BacterioSTATIC

Front 11

Ethambutol- PK, Use

Back 11

- excreted unchanged mostly in urine
Use: first line treatment of TB

Front 12

Ethambutol- Tox, Use

Back 12

- Optic neuritis - loss of visual acuity and red green blindness. Peripheral neuritis, headache, skin rash. Thus must do monthly tests for visual acuity
- Use: First line treatment for TB

Front 13

Which drugs are included in 2nd line TB treatment? When are they used instead of 1st line?

Back 13

- Streptomycin (SM), cycloserine, ethionamide, para-amino salicylic acid
- Used due to resistance to 1st line, failure of clinical response to 1st line, adverse drug rxns, and when expert guidance is available to deal with toxic side effects

Front 14

Streptomycin (SM)- Use, MOA

Back 14

Use: TB second line drug
MOA- inhibs bact prot synth, interferes with initiation complex of peptide formation and causes misreading of mRNA which causes incorporation of incorrect aa's and non functional proteins

Front 15

Streptomycin (SM)- PK, Use

Back 15

- IV or IM (not orally), distributed in most tissues but has LOW intracellular concentrations and is effective against extracellular bacilli. Excreted unchanged
Use: Second line treatment for TB

Front 16

Streptomycin ( SM)- Toxicity

Back 16

- Ototoxicity, vestibular dysfunc (falling in dark rm--irreversible), auditory disturbances, renal injury, and hypersensitivity. Precaution is routine audiometry

Front 17

Paramino salicylic acid- Use, MOA

Back 17

- Use - second line drug TB
- MOA- competes with PABA for mycobacterial dihydropteroate synthetase (folate biosynthesis)-- BACTERIOSTATIC

Front 19

Para salicylic acid- toxicity

Back 19

Tox-thyroid, GI (less symptoms when given with food and antacids), hepatitis
- PAS now used infrequently b/c other drugs are better tolerated

Front 20

Ethionamide- Use, MOA

Back 20

Use- Second line treatment for TB
MOA- related to INH and blocks synthesis of mycolic acids

Front 22

Ethionamide- toxicity, use

Back 22

- GI, liver, neurological symptoms
- pyrodoxine(B6) can decrease neuro side effects
Use: Second line treatment TB

Front 23

Clofazimine- Use, MOA, PK

Back 23

Use: Second line treatment for TB, but also PB and MB leprosy
MOA: inhibits bacterial DNA synth
PK: concentrates in reticuloendothelial system and slowly released from these deposits, metabolized into inactive metabolites, is excreted mainly in the feces. T 1/2= 10 days!

Front 24

Clofazamine- toxicity, Use

Back 24

- GI, drug accums in tissue and causes red brown skin color (leprosy and TB pts do not like b.c it is identifier)
- causes discoloration of skin, urine, & feces
Use: 2nd line TB and MB leprosy

Front 25

Cycloserine- Use, MOA

Back 25

Use: TB (neither first nor second line)
MOA: acts by inhibiting cell wall synth-- rarely used b.c ↓ efficacy and adverse side effects

Front 26

Fluoroquinolones- Use, MOA

Back 26

Include the -floxacins, good for resistant TB.
Use- TB, atypical mycobacterium
MOA- inhibits topoisomerase II

Front 27

Fluoroquinolones- meds and usefulness

Back 27

- ciprofloxacin, moxifloxacin, levofloxacin etc, Mox is most active against M tuberculosis and is useful for drug resistant TB, will probs become more useful as more atypical mycobacterium infections happen
- also used for atypical mycobacterial infections

Front 28

What number of drugs should be used to treat TB, why and is prolonged treatment necessary?

Back 28

Must use multiple drugs b.c bacteria will develop resistance, and prolonged treatment is necessary for persistent bacilli that have mutated

Front 29

Who is preventative chemotherapy(INH monotherapy for 6 mos) recommended for?

Back 29

- ppl with positive TB test, contact with infective TB case

Front 30

When is DOT (direct observed therrapy) recommended?

Back 30

- non compliance (treatment failure, MDR)
- supervised ther has higher success rate

Front 31

Leprosy (Hansen’s Disease)

Back 31

chronic infectious disease caused by Mycobacterium leprae (Hansen’s bacillus), affects the skin, the peripheral nerves, mucosa of the upper respiratory tract and also the eyes

Front 32

Mycobacterium leprae is ___, ___ shaped, and has waxy coating
- M. leprae stains with ___ rather than trad. gram staining
- M. leprae is obligate ____ parasite

Back 32

1. gram positive
2. rod shaped
3. carbol fuchsin staining
4. obligate intracellular

Front 33

What are the two major forms of leprosy?

Back 33

- Tuberculoid (loss of skin sensation, hypopigmentation. thickened auricular nerve) and multibacillary (aka lepromatous leprosy --symetric thickened skin lesions, blindness as disease advances, most cases in US are MB)

Front 34

What are the drugs used to treat leprosy?

Back 34

MDT-- Rifampin, Cloazamine, Dapsone for MB leprosy
Rifampin and Dapsone for PB leprosy

Front 35

Dapsone- Use, MOA

Back 35

Use: Both MB and PB leprosy
MOA: inhibits folate synthesis

Front 36

Dapsone- toxicity

Back 36

- drug well tolerated, though some fever, GI, skin rash, and exfoliative dermatitis

Front 37

Rifampin- toxicity, use

Back 37

- toxicity-slightly reddish urine
Use: first line treatment for TB

Front 38

Clofazamine- toxicity, use

Back 38

- toxicity- non toxic though causes skin discoloration
- use:2nd line TB and Multipbacillary leprosy (lepromatous lepsory)

Front 39

Treatment of atypical myccobacteria (nontuberculous bacteria)?

Back 39

Treatment- Azithromycin, Ethambutol
- rifaubutin can be used additionally
- Fluoroquinolones such as Moxifloxacin