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RHS > L22- Mycobacterial Antibiotics > Flashcards

L22- Mycobacterial Antibiotics Flashcards

1
Q

Mycobacteria is difficult to treat because of:

  • (1) location
  • (2) intrinsic property
  • (3) required therapy
A

1- intracellular location

2- resistance to most antibiotics + ability to develop resistance quickly

3- combination therapy for mos-yrs

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2
Q

Tb is caused by (1), described as a (2- size, shape, respiration, motility) type bacteria. TB is a serious infection of the (3) organs.

A

1- mycobacterium tuberculosis
2- small, aerobic, non-motile, bacillus (divides every 16-20 hrs)
3- lungs, GUT, skeleton, meninges

Note- believed 1/3 of population is infected, latent or active

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3
Q

list the 1st line Tb drugs (hint- 5)

A
  • isoniazid
  • rifampin
  • rifabutin* (1st line in HIV pts)
  • ethambutol
  • pyrazinamide
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4
Q

list the 2nd line Tb drugs (hint- 4)

A
  • streptomycin
  • ethionamide
  • levofloxacin
  • amikacin
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5
Q

list the 3 goals of Tb therapy (include generally what it takes to accomplish them)

A

1) kill bacilli
2) prevent emergence of drug resistance
3) eliminate persistent bacilli from host tissue –> prevent relapse

-multiple drugs for a significant period in time is required to meet these goals

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6
Q

Tb therapy:

  • (1) is required before therapy
  • (2) is required in therapy
  • (3) is recommended for difficult patients
A

1- antibiotic susceptibility testing

2- 3-4 drug combination regimen

3- DOT, directly observed therapy: for non-compliant Pts or highly resistant strains

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7
Q

what are the 2 categories of high risk Tb patients (Latent Tb, since it effects recommended therapy)

A
  • recently infected Tb patients

- Pts with medical conditions that weaken the immune system

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8
Q

what are the criteria for high risk Tb patients for those that have been recently infected

A
  • close contact with infected Tb person
  • person who has emigrated from an area with high Tb rate
  • children <5y/o w/ +Tb test
  • groups with high Tb transmission rates
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9
Q

what are the common conditions that weaken the immune system and put a person at high risk for Tb

A
  • HIV+
  • substance abuse
  • DM
  • organ transplants
  • severe kidney disease
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10
Q

(1) is a synthetic agent of pyridoxine. It is a (1st/2nd)-line Tb drug for (mono-/combination) therapy in active infections and (mono-/combination) therapy in latent infections.

A

1- Isoniazid
2- 1st line
3- combination (active)
4- monotherapy (latent)

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11
Q

______ is the sole drug of choice for latent Tb infections

A

isoniazid

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12
Q

Isoniazid is a pro-drug activated by (1). It aims to target (2) and (3) enzymes which function to (4).

A

1- myobacterial catalase peroxidase (KatG)
2- enoyl acyl carrier protein reductase (InhA)
3- β-ketoacyl-ACP synthase (KasA)
4- mycolic acid synthesis

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13
Q

Isoniazid uses:

  • (1) effects against bacilli in stationary phase
  • (2) effects against rapidly dividing bacilli
  • specific for (3)
  • if used alone for (3), (4) is almost guarantee to occur
A

1- bacteriostatic effects (prevents growth, stagnant)
2- bacteriocidal effects (destroys bacteria)
3- M. tuberculosis (active infection)
4- resistant organisms rapidly emerges

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14
Q

Isoniazid Resistance results from one of the following…. (discuss its tendency for cross-resistance)

A

Chromosomal mutations:

  • deletion of KatG
  • mutation of acyl carrier proteins
  • InhA overexpression

Note- no cross-resistance for other Anti-Tb drugs developed

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15
Q

discuss administration and distribution of Isoniazid

A
  • oral, IV, IM

- diffuses into all body fluids, cells, *caseous material

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16
Q

list the AEs for isoniazid

A
  • peripheral neuritis (correct with pyridoxine supplementation)
  • hepatotoxicity (clinical idiosyncratic hepatitis)
  • CYP450 inhibitor (inc effect of other drugs)
  • lupus-like syndrome, rare
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17
Q

discuss Isoniazid use in pregnancy

A

-generally safe

  • hepatitis risk is inc
  • pyridoxine supplementation use is recommended (prevent peripheral neuritis)
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18
Q

Rifamycins:

  • (1) list the drugs
  • (1st/2nd) line therapy for active Tb
  • (1st/2nd) line therapy for latent Tb
A

1- rifampin, rifabutin
2- 1st line, in combination
3- 2nd line, monotherapy (isoniazid is 1st)

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19
Q

Rifampin uses:

  • (1) type effects against bacilli
  • if used alone for Tb, (2) is almost guarantee to occur
A

1- bactericidal (antimicrobial, antimycobacterial)

2- resistant strains rapidly emerge (therefore usually given in combination)

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20
Q

Rifampin MOA

A

-binds β-subunit of bacterial DNA-dependent RNA polymerase

–> blocks transcription // inhibition of RNA synthesis

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21
Q

list the organisms Rifampin is used against in therapy

A
  • Intracellular and Extracellular Mycobacteria: M. tuberculosis, M. kansasii
  • Gram+/- organisms
  • MRSA
22
Q

Rifampin resistance:
-(1) mutation is required in (2) gene of (3) protein, causing (4)
OR
-decrease in (5) in bacteria

A

1- point mutation
2- rpoB gene
3- β-subunit of bacterial DNA-dependent RNA polymerase
4- dec affinity of β-subunit for Rifampin

5- dec permeability

23
Q

Rifampin clinical applications:

  • (1) discuss uses in Tb
  • (2) discuss its use in Leprosy
  • prophylaxis use in (3) and (4) patients
  • used in (5) infections along with (6); hint- a very common highly resistant infection
A

1- 1st line combination for active infections, 2nd line (for isoniazid intolerant Pts) for latent infections

2- delays resistance to Dapsone

3- those exposed to Menigintis
4- those in contact with H. influenza (children)

5- MRSA
6- vancomycin

24
Q

Rifampin pharmacokinetics:

  • (1) route of administration
  • (2) distribution
  • (3) excretion mechanism
  • (4) other metabolism effects
A

1- oral, parenteral
2- well distributed, including CSF
3- feces mainly
4- strong CYP450 inducer (dec levels of other drugs)

25
Q

Rifampin AEs:

  • (1) are common effects
  • (2) are occasional effects
  • (3) noticeable harmless effect
  • (4) metabolism effect
  • (5) use in pregnancy
A

1- light chain proteinuria, GI distress
2- thrombocytopenia, rashes, nephritis, liver dysfunction
3- orange-red body fluid colors (urine mainly noticed)
4- strong CYP450 inducer (dec levels of other drugs)
5- safe in pregnancy

26
Q

Rifabutin:

  • (1) and (2) are why it would be used over Rifampin
  • (3) are its recommendations during pregnancy
A

1- preferred for HIV Pts b/c less CYP induction
2- Pts intolerant to Rifampin
3- no data for use in pregnancy

27
Q

Ethambutol is used to treat (1) in combination with (2). If used in monotherapy for (1), (3) is almost guaranteed to occur due to mutations in (4).

A

1- all susceptible forms of Tb
2- (ethambutol), isoniazid, pyrazinamide, rifampin
3- acquired resistance
4- emb gene

28
Q

Ethambutol MOA

A
  • inhibits arabinosyltransferase

- decreased carbohydrate polymerization of cell wall

29
Q

Ethambutol AEs:

  • (1) is an important dose-dependent effect, therefore not is used in (2) patients
  • (3) are the observed AEs
  • (4) use in pregnancy
A

1- visual disturbances, e.g. red-green color blindness
2- children too young for vision testing
3- HA, confusion, hyperuricemia, (rarely peripheral neuritis)
4- safe in pregnancy

30
Q

Pyrazinamide is activated by (1) process into (2). It is used as (1st/2nd) line treatment for Tb.

A

1- hydrolyzed
2- pyrazinoic acid
3- 1st line Tb Tx in combination (RIPE drugs)

31
Q

list the methods mycobacteria have for Pyrazinamide resistance

A
  • lack pyrazinamidase

- inc drug efflux

32
Q

Pyrazinamid pharmacokinetics:

  • (1) discuss absorption and distribution
  • dose adjustments are needed in (2) patients
A

1- well absorbed (high F), well distributed (including CSF)

2- renal or hepatic insufficient patients

33
Q

Pyrazinamide AEs:

  • (1) is the common AE
  • (2) is a similar AE to (1) because (3) is also an AE, but rare because it usually requires a predisposition
  • (4) are the other AEs
  • (5) use in pregnancy
A

1- nongouty polyarthralgia (40% Pts)
2- acute gouty arthritis
3- hyperuricemia
4- hepatotoxicity, myalgia, GI irritation, porphyria, rash, photosensitivity
5- only used in pregnancy if the benefits outweigh the risks

34
Q

Streptomyocin is a (1) type antibiotic, with a (2) MOA.

A

1- aminoglycoside

2- binds ribosome –> inhibits protein synthesis

35
Q

Streptomyocin AEs (include use in pregnancy)

A
  • ototoxicity
  • nephrotoxicity

-category D for pregnancy: only used if benefits outweigh the risks

36
Q

Streptomyocin is used for (1) type bacteria, usually in a (2) regimen for the following diseases, (3).

A 
1- drug-resistant
2- combination
3: (life-threatening Tb disease)
-meningitis
-miliary dissemination
-severe organ tuberculosis
37
Q

Levofloxacin is a (1) type antibiotic, with a (2) MOA.

A

1- fluoroquinolone

2- inhibits bacterial DNA replication

38
Q

Levofloxacin AEs (include use in pregnancy)

A
  • Connective Tissue problems: avoid in pregnancy, nursing mothers <18 y/o – Black Box Warning
  • photosensitivity
39
Q

2nd line Tb drugs:

  • (1) are aminoglycosides used for (2) situations
  • Levofloxacin is always is used in combination for (3) situations
  • Ethionamide is similar to (4) drugs, has (5) AEs

-Note- all have significant (6) effects

A

1- streptomycin, amikacin
2- MDR strains (+ streptomycin resistance for amikacin use)
3- 1st-line drug resistant strains
4- isoniazid
5- GI irritation, neurological effects, hepatotoxicity, endocrine effects
6- **teratogenic

40
Q

describe the Drug Regimens for Latent Tb

A

1st line) Isoniazid, 6-9 mos

2nd line) rifampin, 4 mos

41
Q

discuss the standard Drug Regimens for Active Tb (hint- 2 regimens)

A

1:
i) initial phase 8 wks: RIPE combination (rifampin, isoniazid, pyrazinamide, ethambutol)
ii) continuation phase 18 wks: rifampin, isoniazid

2:

i) initial phase, 8 wks: rifampin, isoniazid, ethambutol
ii) continuation phase 31 wks: rifampin, isoniazid

42
Q

Leprosy, aka (1) disease, is caused by (2). It mainly causes (3). Most cases are found in (4) part of the world.

A

1- Hansen’s disease
2- Mycobacterim leprae, M. lepromatis
3- primary granulomatous disease of peripheral nerves and URT mucosa
4- India, 70% cases

43
Q

what is the pharmacological recommendation for Leprosy (by the WHO)

A
  • dapsone
  • clofazimine
  • rifampin
44
Q

(1) is a Leprosy drug structurally related to sulfonamides. It has a (2) effect on mycobacterium growth. Besides leprosy treatment, it also is used to treat (3) infections.

A

1- dapsone
2- bacteriostatic (prevents growth –> stagnant)
3- pneumonia due to P. jiroveci in HIV pts

45
Q

dapsone MOA

A
  • inhibits dihydropteroate synthertase

- -> inhibits folate synthesis

46
Q

Dapsone pharmacokinetics:

  • (1) discuss absorption and distribution
  • (2) is respiratory form of dapsone
A

1- well absorbed (high F), well distributed (high levels in skin)
2- acedapsone

47
Q

Dapsone AEs:

  • (1) is key effect, especially in susceptible patients
  • (2) other AEs
  • (3) metabolism effects
A

1- hemolysis (especially in G6PD deficiency)
2- GI irritation, fever, hepatitis, methemoglobinemia
3- CYP450 inhibitor (elevated levels of other drugs)

48
Q

Clofazimine AEs:

  • (1) properties allow it to generate (2)
  • (3) hallmark AE
  • (4) other AEs
A

1- redox properties
2- cytotoxic oxygen radicals
3- Red-Brown discoloration of skin
4- GI irritation, eosinophillic enteritis

49
Q

Describe Leprosy Tx recommendations based on type

A

Pauci-bacillary (PB): 1-5 skin lesions
-2 drug regimen, dapsone + rifampin for 6 mos

Multi-bacillary: >5 skin lesions
-3 drug regimen, dapsone + rifampin + clofazimine for 12 mos

50
Q

Describe Leprosy Tx recommendations based on type

A

Pauci-bacillary (PB): 1-5 skin lesions
-2 drug regimen, dapsone + rifampin for 6 mos

Multi-bacillary: >5 skin lesions
-3 drug regimen, dapsone + rifampin + clofazimine for 12 mos

51
Q

Atypical Mycobacteria:

  • (1) communicability
  • drug susceptibility is in relation to (2) disease
  • (3) therapy is requires (include why)
A

1- not transmission person-to-person, although present in environment
2- M. tuberculosis drugs
3- combination therapy b/c of drug resistance

RHS (35 decks)

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