Pharm Test 2: Antimycobacterial Drugs

Front 1

1)Why are mycobacteria different from other bugs? How do you treat? How long does therapy take?

Back 1

1)They are intrinsically resistant to most antibiotics, and they stay dormant for awhile allowing for my time to develop resistance. They REQUIRE COMBO THERAPY (3 to 4 drugs). Months to Years (thus compliance can be low, and resistance can develop)

Front 2

1)Difference between first line and second line drugs?

2)When are DOT regimens recommended?

Back 2

1)First line given when resistance not going to be a problem

2)Directly Observed Therapy regimens recommended in noncompliant patients or resistant strains (too makes sure compliance is 100 percen)

Front 3

Isoniazid

1)What is it
2)Is the only drug used to treat?
3)MOA
4)What are the enzyme needed to make mycolic acid?

Back 3

1)First line agent, Most Potent of Anti TB drugs
2)Latent Infections (no symptoms) (not dividing and not risk for spread)

3)Needs to be activated by Catalase-peroxidase (thus resistance is high, beacuse anything that can mutate enzyme, will cause resistance)->targed enzymes involved in making Mycolic Acid (part of cell TB wall)

4)Enoyl Acyl Carrier Protein Reductase (AcpM)
Beta Ketoacyl ACP Synthase (KatG)

Front 4

Isoniazid

5)Bacteriostatic or Cidal
6)If use alone on non latent orgs, what happens?

7)How does resistance develop?
8)If resistant to Isoniazid, does that mean are resistant to other drugs?

Back 4

5)Bacteriostatic when bacilli in stationary phase
Bacteriocidal when bacilli in diving stage

6)Resistant organisms rapidly emerge

7)Mutation or deletion of KatG
Mutation of Acyl Carrier Proteins
Overexpression of inhA

8)NO; Cross resistance between other anti TB drugs does not occur

Front 5

Isoniazid

9)Absorption impaired by...
10)How is it given

11)How is it metabolized

Back 5

9)food and aluminum containing Antacids
10)Oral, IV, IM

1)it undergoes N-acetylation and hydrolysis to become inactive (thus depending if u are fast or slow acetylator, half life of drug changes)(THUS EVERY PATIENT RESPONDS TO THIS DRUG DIFFERENTLY)

Front 6

Isoniazid

12)AE
13)What does it do to CYP 450
14)Any special AE

Back 6

12)Inc aminotransferases
Peripheral Neuritis (Parathesis of hands and Feet)(d/t dec Pyroxidine->THUS GIVE PYROXIDINE SUPP)
Hepatitis (elderly)
CNS Effects)
Hypersensitivity

13)Inhibits

14)Lupus Like Syndrome (anti-ANA antibodies in 20 percent)

Front 7

Rifamycins

1)What are the 3 of them?
2)What are they

Back 7

1)Rifampin, Rifabutin, Rifapentine
2)First Line Drugs (Used in Combo)

Front 8

Rifampin

1)Cidal or STatic?
2)MOA for all 3 in Category
3)Bugs it works against?

Back 8

1)Cidal

2)blocks transcription of bacterial DNA depended RNA polymerase -> inhibits RNA synthesis (thus specific for bacteria, not human)
3)M.tuberculosis, M.kansasii

Front 9

Rifampin

4)How does resistance develop

5)Effect on CYP P450

6)AE

7)Effect on Pregnant?

Back 9

4)point mutations in rpoB (gene for RNA polymerase) -> decreased affinity of bacterial DNA depended RNA polymerase for Drug

5)STRONG INDUCER (if give with isoniazid, still get induction, not inhibition)

6)Hepatotoxicity (more like when used with isoniazid)
Harmless Orange Color in Body Fluids (can stain ur contacts orange)

7)SAFE in pregnancy (isoniazid has inc risk of hepatotoxicity and thus need to give pyroxidine supps)

Front 10

Rifampin
8)CU
9)DOC

Back 10

8)TB, Latent TB(as sole drug), Leprosy
9)Prophylaxis for Meningitis (DOC)

Front 11

Rifabutin

1)CU
2)AE
3)Pregnancy?

Back 11

1)Preferred drug for TB in HIV patients (d/t no strong induction effect on CYP P450)

2)Similar adverse to Rifampin
Also, Uveitis, Skin Hyperpigmentation, Neutropenia

3)Dont use, because not enough data on it

Front 12

Rifapentine

1)CU
2)Should it be used alone
3)Pregnancy?

Back 12

1)Longer Half life then other 2, so permits weekly dosing

2)No only in COMBO
3)Dont use, not enough data

Front 13

Ethambutol

1)What is it?
2)What bugs does it work on
3)MOA

4)Use in combo with what?

Back 13

1)First Line agent (only use when kno TB is suscpetible)

2)M. tuberculosis, M. kansasii

3)inhibits arabinosly transferases (normally makes part of mycobacterial cell wall)

4)Pyrazinamide, Izoniazid, and Rifampin

Front 14

Ethambutol

5)How does resistance develop?

6)is its metabolism affected by other drugs?

7)AE
8)Pregnancy?

Back 14

5)mutation in EMB gene (occurs rapidly if drug used alone)

6)Not really, large fraction eliminated unchanged in urine

7)DOSE DEPENDENT Visual Problems (dec visual acuity, Red Green color blindness, Retinal Damage)
Decreased Urate Excretion ->Gout
8)Safe for Use

Front 15

Pyrazinamide

1)What is it?
2)Use in combo with which drugs
3)Must be enzymatically activated to what?
4)How do strains become resistant?

Back 15

1)First Line Agent

2)Isoniazid, Rifampin, and Ethambutol
3)Pyrazinoic Acid
4)lack Pyrazinamidse
Increased Efflux of Drug

Front 16

Pyrazinamide

5)AE
6)Pregnancy?

Back 16

Hepatotoxicity (more at risk when use with other drugs that also cause it)
Nongouty Polyarthralgia
Use When benefits outweight risk

Front 17

Streptomycin

1)What is it?

2)CU

3)AE
4)Contra

Back 17

1)second line (used for drug resistant strains)

2)used in combo for Life Threatening TB (meningitis, miliary spread, Severe Organ TB)

3)Ototoxicity
Nephrotoxicity
Neurotoxicity (reversible)
Vertigo and Hearing Losee (most common, permanent)

4)Pregnancy

Front 18

Amikacin

1)What is it?
2)CU
3)AE
4)Contra

Back 18

1)Second Line
2)For Streptomycin or Multi Drug Resistant Strains

3)Similar to Streptomycin
4)Teratogenic (DONT GIVE TO PREGNANt)

Front 19

Levofloxacin

1)what is it?
2)CU
3)Contra

Back 19

1)Second Line

2)First Line Drug Resistant Strains

3)Teratogenic (Dont give to pregnant)

Front 20

Ethionamide

1)What is itt?
2)AE
3)Contra

Back 20

1)Second Line, Used Last

2)Severe GI Irritation
Neuro
Hepatotoxicity
endocrine

4)Teratogenic (Dont give to pregnant)

Front 21

1)How to treat Latent TB

2)What 2 drugs can you give and for how long

Back 21

1)Can give solely one drug

2)Isoniazid for 6 to 9 months
Rifampin for 4 months

Front 22

Regiment for Empiric Treatment of TB

4 Drugs Therapy:
-Initiation Phase:
1)4 drug combo and duration
-Continuation Phase:
2)2 Drug Combo and duration

3 Drug Therapy
-Initiation Phase:
3)3 Drug Combo and Duration
-Continuation Phase:
4)2 Drug Combo and Duration

5)If no strain susceptible to isoniazid or rifampin, what do you do?

Back 22

1)Isoniazid, Rifampin, Pyrazinamide, Ethambutol for 8 weeks

2)Isoniazid and Rifampin for 18 weeks

3)Isoniazid, Rifampin, and Ethambutol for 8 weeks

4)Isoniazid and Rifampin for 31 weeks

5)Can knock off ethambutol from therapy (start with 3 or 2 drugs)

Front 23

1)Give if know resistant to Isoniazid (+/-Streptomycin) and Duration

2)Give if know resistant to Isoniazid and Rifampin (+/- Streptomycin)

Back 23

1)Rifampin, Pyrazinamide, Ethambutol for 6 months

2)Fluoroquinolone, Pyrazinamide, Ethambutol, and Injectable Agent (eg: streptomycin)
+/- Second Lines for 2 Years

Front 24

3)Give if know resistant to Isoniazid, Rifampin (+/-Streptomycin) AND other First Line Drugs

Back 24

3)Fluoroquinolone, Streptomycin,
+/- 2 Second Lines for 2 Years

4)Isoniazid, Ethambutol, Fluoroquinolone for 12-18 months
Supplement Pyrazinamide for first 2 months

Front 25

Leprosy (Hansen's Disease)

1)Caused by and 70 percent in
2)effectS?

3)What 3 drugs are recommended for treatment and how do you give?

Back 25

1)mycobacterium leprae and mycobacterium lepromatis; India

2)granulomatous disease of peripheral nerves and mucosa of upper RT (WHO provides free treatment for this)

3)Dapsone, Clofazimine, and Rifampin; IN COMBINATION d/t resistance

Front 26

Dapsone

1)Static or Cidal?
2)MOA
3)CU
4)Metabolized?
5)What is Acedapsone

Back 26

1)Static
2)inhibits folate synthesise

3)Leprosy
p. jiroveci in HIV Positive

4)Hepatic Acetylations (so effected by slow and fast acetylators)
5)Repository form (longer half life)

Front 27

Dapsone

6)AE

Back 27

6)Hemolysis
Erythema nodosum Leprosum (prevent with steroids)

Front 28

Clofazimine

1)Cidal or Static

Back 28

1)Bactericidal to M. Leprae

2)binds to DNA and inhibits replication

3)Red Brown Discolored Skin
Eosinophilic Enteritis
(NO ERYTHEMA MARGINOSUM DEVELOPS, because drug is anti inflam)

Front 29

How to treat

1)Pauci Bacillary (PB, 1 to 5 Skin lesions)

2)Multi Bacillary (>5 skin lesions)

Back 29

1)2 drugs: Rifampin and Dapsone for 6 months

2)3 drugs: Rifampin, Clofazimine, and Dapsone for 12 months

Front 30

Treat Atypical Mycobacteria:

1)M. kansaii (resembles TB)
2)M. marinum
3)M. avium (Pumonary)

4)M. chelonae (Abscess)
5)M. fortuitum

Back 30

1)Isoniazid, Rifampin, and Ethambutol

2)Any of these 2 drugs: Rifampin, Ethambutol. Clarithromycin, Minocycline, Doxycycline, Sulfonamides)

3)Clarithromycin, Rifampin, Ethambutol

4)Clarithromycin
5)Amikacin, Cefoxitin, Levolfoxacin, Sulfonamides, Imipenem