EXAM #4: TREATMENT OF MYCOBACTERIA Flashcards Preview

Pharmacology > EXAM #4: TREATMENT OF MYCOBACTERIA > Flashcards

Flashcards in EXAM #4: TREATMENT OF MYCOBACTERIA Deck (49):
1

What kind of infection is caused by MAC in the immunocompetent?

Pulmonary

2

What kind of infection is caused by MAC in the immunocompromised?

Disseminated

3

What are the important characteristics of Mycobacterium?

1) Rod-shaped
2) Lipid rich cell wall with MYCOLIC ACID
3) Poor gram staining
4) ACID FAST
5) Slow growing*

*Makes these bacteria challenging drug targets*

4

What cells can Mycobacterium replicate in?

Macrophages

5

How is Mycobacterium Tuberculosis transmitted?

Respiratory droplets

6

What is Latent TB?

Infection with INACTIVE MTB
- Asymptomatic
- PPD positive
- Negative CXR

7

What is Active TB?

Active infection with MTB
- Symptomatic
- Positive CXR
- Infectious

8

What are the obstacles to MTB treatment?

1) Slow growing/ dormant
2) Develop resistance
3) Toxicity of drugs

9

What are the solutions to the obstacles of MTB treatment?

1) Multiple drug regimines
2) Drugs taken regularly
3) Drug therapy for sufficient time

10

What is direct observed therapy?

Therapy that is directly observed by a public health worker to ensure compliance

11

List the drugs that are approved for the treatment of TB.

Rifamycin
Streptomycin
Isoniazid
Ethionamide
Pyrazinamide

12

What is the most important drug for treating both latent and active TB? How much resistance is seen to this drug?

Isoniazid

*10% of TB strains are resistant to TB

13

How is MAC acquired?

- Ingestion of contaminated food and water
- Respiratory droplets (less frequent)

14

How is the preferred treatment for active TB?

1) RIPE therapy for 8 weeks
2) RI only for 18 weeks

Rifampin
Isoniazid
Pyrazinamide
Ethambutol?

15

How is latent TB treated?

Isoniazid for 9 months

16

What is the MOA of Isoniazid (INH)?

Inhibits the synthesis of mycolic acid (cell wall)

*Note that is is given as a Prodrug

17

What enzyme from MTB converts INH into the active form?

Mycobacterial catalase peroxidase enzyme (Kat G)

18

What are the resistance mechanisms associated with INH?

1) Kat G mutations--can't activate the drug
2) Increased mycolic acid synthesis

19

How is INH metabolized?

Acetylation

20

What is the implication of "slow acetylation" in INH therapy?

More toxicity seen in slow acetylators

21

What are the major toxicities associated with INH?

1) Hepatitis
2) Peripheral neuropathy

*Note that the hepatitis seen with INH is WORSE in alcoholics*

22

What increases the risk of peripheral neuropathy with INH aside from slow acetylation?

1) Malnourishment
2) Alcoholism
3) DM
4) AIDS

23

What is the MOA of Rifampin?

Inhibition of RNA synthesis
- Binds bacterial DNA-dependent RNA polymerase

24

What causes resistance to Rifampin?

Point mutations in bacterial DNA-dependent RNA polymerase

25

What is the most common side effect associated with Rifampin?

Orange-red color imparted to
- Urine
- Feces
- Sweat
- Tears

....etc.

26

What important drug-drug interaction is associated with Rifampin?

Increased elimination of many antiretrovirals in HIV

27

What drug can be substituted for Rifampin in an HIV positive individual with active TB?

Rifabutin

28

What is the MOA of Pyrazinamide?

Unknown but likely impedes cell wall synthesis

29

How is Pyrazinamide used in clinical practice?

In combination with other anti-TB drugs--NOT by itself

30

What is unique about Pyrazinamide in terms of its action?

Prefers an acidic enviornment i.e. prefers to act in acidic marophages treating intracellular MTB

31

What is the mechanism of resistance to pyrazinamide?

- Pyrazinamide is a prodrug that requires PYRAZINAMIDASE to become active
- Mutations in this enzyme lead to resistance

32

What adverse effect is associated with Pyrazinamide?

Gout/ Hyperuricemia

33

What is the MOA of Ethambutol?

Inhibits arabinosyl transferases that are involved in mycobacterial cell wall synthesis

34

Clinically what is unique about Ethambutol?

Also good for MAC

35

What causes resistance to Ethambutol?

Mutations in arabinosyl transferases

36

What are the adverse effects associated with Ethambutol?

1) Retrobulbar neuritis
2) Hyperuricemia

37

What is Streptomycin?

Aminoglycoside antibiotic
- Interferes with bacterial protein synthesis

38

What is the utility of Streptomycin in treatment of TB?

Currently used for the treatment of RESISTANT TB

39

What are the adverse effects associated with Streptomycin?

Ototoxicity
Nephrotoxic

40

What is a good drug to treat MAC infections (disseminated) in the immunocompromised?

Rifabutin

41

Outline the combination therapy for MAC infection.

1) Macrolide
2) Rifampin or rifabutin
3) Ethambutol
4) Streptomycin

42

What are the two forms of Leprosy?

- Lepromatous
- Tuberculoid

43

What is Lepromatous Leprosy?

- Disfiguring skin lesions
- Negative skin test
- Large number of organisms in tissue

44

What is the Tuberculoid form of Leprosy?

- Milder
- Hypopigmented plaques
- Positive skin test
- Few organisms

45

How is Leprosy treated?

1) Dapsone
2) Clofazimine
3) Rifampin

*These drugs are taken for YEARS*

46

What is the MOA of Dapsone?

PABA analog that inhibits folate synthesis

47

What adverse effect is associated with Dapsone?

Non-hemolytic anemia

48

What is the MOA of Clofazimine?

Bactericidal dye with unknown MOA

49

What is the adverse effect associated with Clofazimine?

Red-brown to black changes in skin pigmentation

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