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Respiratory 2 > Sulfas, Antifolates, Fluoros - Fitzpatrick > Flashcards

Sulfas, Antifolates, Fluoros - Fitzpatrick Flashcards

1
Q

Sulfamethoxazole-Trimethoprim (TMP-SMZ) - Main uses in this section (3)

A
  • PREVENTING or treating Toxoplasmosis in immunosuppressed patients
  • PREVENTING or treating Pneumocystis jiroveci pneumonia in immunosuppressed patients
  • H. influenza sinusitis
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2
Q

Adverse effects of TMP-SMZ (5)

Seen ESPECIALLY in who?

A
  • Rash (Steven-Johnson) - LIFE THREATENING
  • Kernicterus (and jaundice) - NEWBORNS
  • Hemolysis in G6PD deficiency patients

Especially seen in AIDS patients

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3
Q

Sulfadiazine-Pyrimethamine is used clinically for what?

A

TOXOPLASMOSIS

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4
Q

Sulfonamide drugs - MoA

A

Competitive inhibition of DIHYDROPTEROATE SYNTHASE (resembles PABA) –> inhibits bacterial folic acid synthesis –> inhibits nucleic acid synthesis and replication

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5
Q

TMP-SMZ is a classic example of _____

A

Antibiotic synergy

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6
Q

Trimethoprim - MoA

How is this synergistic w/ Sulfamethoxazole?

A

Dihydrofolate reductase inhibitor

This is the 2nd enzyme in the folic acid synthesis pathway in bacteria. Thus, the TMP-SMZ combo inhibits BOTH of the steps.

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7
Q

Organisms that are sensitive to Sulfonamides must do what?

Are humans sensitive? Why or why not?

A

Build folic acid DE NOVO

NO - we get our folate from diet

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8
Q

Organisms sensitive to TMP-SMZ (+ condition caused) (7)

A
  • E. coli (cystitis, prostatitis)
  • Proteus (cystitis, prostatitis)
  • Salmonella (diarrhea)
  • Shigella (diarrhea)
  • H. influenza (sinusitis)
  • Pneumocystis jiroveci (pneumonia)
  • Toxoplasma (encephalitis)
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9
Q

3 ways for resistance to TMP-SMZ

A
  • Dihydropteroate synthase mutation
  • DHFR mutation
  • DHFR overexpression
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10
Q

Can you use TMP-SMZ for MRSA?

A
  • Yes, but only in the community in areas where it is known that the MRSA strain is susceptible to it
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11
Q

A pregnant woman takes TMP-SMZ for an infection. At birth, the baby appears yellow and shows signs of neurologic deficit. Explain.

A

SMZ displaces bilirubin from albumin. In baby, bilirubin cannot be broken down, thus builds up in skin (jaundice) and brain (kernicterus).

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12
Q

SMZ is contraindicated in who?

A

Near-term pregnant women, neonates

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13
Q

A patient is taking a Sulfonamide for an infection, and soon develops weakness, hematuria, jaundice, etc. The patient remembers that she has a deficiency in G6PD. Explain.

A

Sulfonamides cause increased reactive oxidants (oxidative stress). In G6PD deficiency, glycolysis cannot be used to turn NADP+ into NADPH, and thus glutathione. As a result, the oxidants and H2O2 build up, causing hemolytic anemia.

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14
Q

TMP is contraindicated in who? Why?

A

Pregnant women at months 2-3 (end of 1st trimester)

  • High folate need by fetus at that time
  • Without it –> CV defects and oral clefts
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15
Q

Fluoroquinolones - MoA

A

DNA gyrase (topoisomerase 2) and topoisomerase 4 inhibition –> DNA dysruption

- DNA gyrase = gram (-)
- Topoisomerase 4 = gram (+)
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16
Q

Mechanisms of resistance to Fluoroquinolones (3)

A
  • DNA gyrase / topoisomerase mutation
  • Cellular membrane efflux mechanisms
  • Decreased porins - MULTI-DRUG RESISTANCE
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17
Q

3 ways that porins can be decreased and lead to multi-drug resistance in a bacterial strain

A
  • Loss completely
  • Mutation (non-functional)
  • Decreased expression of the porin
18
Q

Difference in a bacterial strain being COMPLETELY resistant to a Fluoroquinolone vs. being PARTIALLY resistant

A 
Complete = no active porins
Partial = decreased expression/production of porins
19
Q

2nd generation Fluoroquinolone - drug

A

Ciprofloxacin

20
Q

3rd generation Fluoroquinolone - drug

A

Levofloxacin

21
Q

4th generation of Fluoroquinolone - drug

A

Moxifloxacin

22
Q

Choosing a fluoroquinolone, even for an unusual bacteria, is often due to what characteristic of the infection?

A

Localized in BONE

23
Q

Due to its penetration into bone, Fluoroquinolone is used to treat what?

A

Osteomyelitis

24
Q

Atypical organisms covered by Fluoroquinolones

A
  • Mycoplasma
  • Chlamydia
  • Mycobacteria
  • Legionella
25
Q

Ciprofloxacin, in addition to the usual Gram (-)’s and the atypical organisms, also is used to treat what 2 other things?

A
  • E. coli

- ANTHRAX

26
Q

Levofloxacin, in addition to the usual Gram (-)’s and the atypical organisms, also is used to treat what other thing?

A

Strep. pneumoniae

27
Q

Moxifloxacin, in addition to the usual Gram (-)’s and the atypical organisms, also is used to treat what 3 other things?

A
  • Gram + cocci
  • Gram + bacilli
  • ANAEROBES
28
Q

In the treatment of _____, Cipro or Levo would be ok choices, but Moxi would NOT.

A

Pseudomonas

29
Q

Treatment of community acquired pneumonia with which Fluoroquinolones?

A

ANY of them

30
Q

Treatment of a pneumonia that is resistant to penicillins and cephalosporins (or hypersensitive, etc.) = ____

A

Fluoroquinolones (any)

31
Q

Treatment of exacerbation of chronic bronchitis

A

Levo, Moxi, or Gemifloxacin

32
Q

Treatment of acute bacterial rhinosinusitis

A

Cipro, Levo, or Moxi

33
Q

Treatment of Nosocomial pneumonia

A

Cipro or Levo

34
Q

Foods/drugs that should be taken SEPARATELY from Fluoroquinolones (3)

Why?

A
  • Antacids w/ Mg or Alum.
  • Calcium foods (dairy)
  • Vitamins w/ iron or zinc

Impaired oral absorption of Fluoroquinolones

35
Q

Compare excretion of the 3 Fluoroquinolones

A
  • Cipro = more urinary, little hepatic
  • Levo = MOSTLY urinary, very little hepatic
  • Moxi = More hepatic, little urinary
36
Q

In a urinary tract infection, which Fluoroquinolones are best based on excretion? Why?

A

Levo and Cipro = better

- More urinary excretion = more action in GU system

37
Q

Contraindications of Fluoroquinolones (2) - Explain them

A

Kids arthritis)
Adults > 60 (accumulation in tendons –> rupture)
Adult gymnasts or climbers (see reason above)

38
Q

Adverse effects of fluoroquinolones

A
  • Bone/tendon/lung accumulation
  • Phototoxicity
  • QT prolongation (inadvertent binding to K+ channels)
39
Q

Fluoroquinolone with the most QT prolongation

A

Moxifloxacin

40
Q

Fluoroquinolones applied _____ do not carry the adverse effects

Ex. infections of the eye can be treated with these via ____

A

Topically

Eye drops (topical)

Respiratory 2 (15 decks)

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