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Pharmacology Antimicrobials > UTI & Miscellaneous > Flashcards

UTI & Miscellaneous Flashcards

1
Q

Sulfonamide Mechanism of Action

A

STATIC
-Interfere w/ microbial FOLIC ACID SYNTH (DHF)
> Competes w/ PABA
> Humans can use preformed folic acid

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2
Q

Sulfonamide Mechanism of RESISTANCE

A
  1. Mutation- produce increased PABA

2. R-Factor- decreased drug permeability

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3
Q

Sulfonamide Available Agents

A

Sulfisoxazole
Sulfamethoxazole
Sulfadiazine

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4
Q

Sulfonamide Half-Life

A

5+ hours

Sulfisoxazole< Sulfmethoxazole< Sulfadiazine (17hrs!)

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5
Q

Sulfonamide Route(s) of Administration

A 
Oral and IV
Except sulfiMETHOXAZOLE (Oral Only!).
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6
Q

Sulfonamide Pharmocokinetics

A
  • Wide & excellent distribution, even CSF
  • Met by liver (acetylation and glucuronidation)
  • Metabolites & free drug excreted in urine
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7
Q

Sulfonamide Spectrum

A

Wide!
Strep, N. meningitis, Nocardia, Chlamydia, E. coli (urine)

Cheap too! Yay.

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8
Q

Sulfonamide Indications

A
  • Uncomplicated UTI
  • Nocardiosis (usually w/ trimethoprim)
  • Toxoplasmosis (w/ pyrimethamine)
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9
Q

Sulfonamide Toxicities

A
  • Crystalluria
  • Kernicterus (displace albumin-bound substance)
  • GI upset
  • ALLERGIC: Stevens-Johnson/rash, Fever, (rare: Hepatic necrosis, Hemolytic anemia, Agrnulocytosis, Aplastic anemia)
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10
Q

This sulfonamide is used orally for ULCERATIVE COLITIS

A

Salicylazosulfapyridine (Azulfidine) or Sulfasalazine

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11
Q

These Sulfonamides are used topically for BURNS

A

Mafenide acetate

Silver Sulfadiazine

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12
Q

This Sulfonamide is used topically-ophthalmic for BACTERIAL CONJUNCTIVITIS

A

Sulfacetamide

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13
Q

Trimethoprim Mechanism of Action

A

STATIC

-Inhibit bacterial DIHYDROFOLATE REDUCTASE (which converts DHF to Tetrahydrofolic Acid)

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14
Q

Trimethoprim Mechanism of RESISTANCE

A

Mutation

R-Factor

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15
Q

Trimethoprim Pharmokinetics

A
  • Wide & Excellent Distribution, CSF too; may concentrate in prostate
  • Most excreted unchanged in urine
  • T1/2= 10 hrs
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16
Q

Trimethoprim Route of Administration

A

Oral

IV (as TMP-SMX)

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17
Q

Trimethoprim Spectrum

A

-fairly wide for susceptible micro-organisms

Pretty cheap

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18
Q

Trimethoprim Indications

A

UTI due to most common urinary pathogens

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19
Q

Trimethoprim toxicity

A

Minimal

-Mimics Folic Acid Deficiency (hematologic)–give folic acid to pts!

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20
Q

Trimethoprim-Sulfamethoxazole Mechanism of Action

A

1: 5 Fixed Ratio
- Sequential blocking in FOLIC ACID SYNTH, synergistic
- Often CIDAL

Super cheap ($4 oral)

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21
Q

TMP/SMX toxicity

A

-same as individual agent

50% rate of adverse effects in AIDS PATIENTS

22
Q

TMP/SMX Spectrum

A

Wide

Includes Strep pneumo, H. flu, most aerobic Gram (-) rods…but NOT PSEUDOMONAS

23
Q

TMP/SMX Indications

A
  1. **UTI!!’*
  2. OM (esp for penicillinase-producing H. flu or w/ beta-lactam allergy)
  3. Acute exacerbations of chronic bronchitis
  4. Enteric infx–salmonella, shigella
  5. Nocardiosis
  6. P. jiroveci pneumonia (tx & px)
  7. Soft tissue & skeletal infx (gram -)
  8. Prophylaxis in neutropenic pts
24
Q

Pyrimethamine Mechanism of Action

A

-Blocks DIHYDROFOLATE REDUCTASE (same as trimethoprim)

25
Q

Pyrimethamine Indications

A

Toxoplasmosis (with sulfadiazine)

Malaria (with sulfadoxine)

26
Q

Quinolone Indication

A

Only for UTI
Weak activity & poor pharmacokinetic profiles
Nalidixic Acid & Cinoxacin

27
Q

Fluoroquiolone advantages over older quinolones

A

-Less toxicity
-Greater antimicrobial activity
>Broader bacterial spectrum
>Lower Inhibitory concentrations
>Lower freq of resistant mutants
>Prob involves increased interactions
w/ target site
-Better GI absorption
-Longer half-lives
-Good for systemic use

28
Q

Fluoroquinolone Agents

A 
Nor
Cipro
O
Levo
Moxi

-floxacin
In order of Older to Newer

29
Q

Fluoroquinolone Mechanism of Action

A
  • Inhibits bac DNA GYRASE (which maintains neg supercoil of xsome & facilitate DNA replication)
  • Rapidly BACTERICIDAL
30
Q

Fluoroquinolone Mechanisms of RESISTANCE

A
  • R-Plasmid
  • Spontaneous mutation»cross-resistance among quinolones, but not w/ other antimicrobials
  • Alteration of DNA gyrase subunit
  • Alteration of permeability (resist other antibiotics)
  • Rate of mutation differs b/w bac= Pseudomonas>E. coli
31
Q

Fluoroquinolone Spectrum

A

Good activity against most GRAM NEG

  • Enterobac
  • Proteus
  • Pseudomonas!
  • H. flu
  • Salmonella, Shieglla, Campylobacter
  • Newer fluoroquinolones increasingly active against GRAM +.
  • Variable activity against mycobac, mycoplasma, Chlamydia, legionella (newer ones are better against Atypical Pneumonia)
  • Not good for Anaerobes
32
Q

These two antimicrobials are nicknamed “Respiratory Quinolones” because they have good activity against STREP PNEUMO (even PCN-resistant strains)

A

Levo & Moxi

These are newer drugs

33
Q

Flouroquinolone Half-Lives

A

Older (Nor & Cipro): 3-6, lower absorption

Newer (O, Levo, Moxi): 10-12, high absorption

34
Q

Fluoroquinolone Route of Administration

A 
Oral 
IV (except for Nor)
35
Q

Flouroquinolones Pharmacokinetics

A
  • Absorption decreased w/ antacids (Mg salts), Iron & Zinc supplements, H2 blockers, milk products
  • Most eliminated in urine through glomerular clearance plus tubular secretion
  • Variably (<50%) met by liver & excreted into bile
  • **Adjust dosage in RENAL FAILURE!
  • Penetrate CSF, PROSTATE, & BILIARY TRACT very well
36
Q

Norfloxacin Indications

A

UTI

Enteric Infx

37
Q

Cipro, O, Levo, Moxi Indications

A

-UTI & enteric infx, like Nor
-Various GRAM NEG infx (incl. pseudomonas)
>DOC for Prostatitis
>Osteomyelitis, soft tissue infx: esp staph
> Resp tract-esp atypicals**
> Prophylaxis in neutropenic hosts
>Comm. resp infx due to S. pneumo, legionella, mycoplasma (esp levo & moxi)
>Moxi: mixed aerobic/anaerobic infx
**Cipro=most active against pseudomonas

38
Q

This Fluoroquinolone is more active against Strep pneumo and less active against Pseudomonas

A

Moxi

39
Q

Fluoroquinolone Toxicities

A
  • Neurotoxicity (seizure @ high levels) in older quinolones
  • *Contraindicated in PEDS & PREG (articular cartilage injury)
  • Tendon rupture (esp Achilles): Black box warning esp in elderly
  • GI
  • CNS
  • Skin rash
  • Elevated liver enzymes
  • Eosinophilia
  • Sleep Disturbance
  • QT prolongation (some quinolones)
  • Superinfection incl. C. diff
  • **Hinder elimination of theophyllines and caffeine!
40
Q

This is the most widely used fluoroquinolone (esp for UTI) and is the most active drug for the most resistant GRAM NEG, esp Pseudomonas. It interacts w/ theophylline. Generic for this drug is available for very cheap.

A

Cipro

41
Q

This drug is the L-isomer of ofloxacin and is good for resp infx (except Pseudomonas–cipro is preferred). It has a low side effect/drug interaction profile and has 1x/day dosing

A

Levo

42
Q

This flouroquinolone is most active against S. pneumo and has fair activity against ANAEROBES

A

Moxi

43
Q

Metronidazole Mechanism of Action

A

-Acts as “electron sink” by depriving cell of reducing equivalents
> metro’s nitro group is reduced by e-transport proteins w/ low redox potential
-CIDAL action against ANAEROBIC bac
-Aerobes are resistant!

44
Q

Metronidazole Route of Administration

A

Oral

IV

45
Q

Metronidazole Pharmacokinetics

A
  • Good absorption
  • T 1/2=8 hrs
  • Met partially by liver (oxidation & glucuronidation)
  • Metabolites and free drug excreted in urine
  • Excellent BRAIN & CSF concentration!
46
Q

Metronidazole Spectrum/Indications

A
  1. Protozoal Infx (esp Trichomoniasis, amebiasis, giardiasis)
  2. Anaerobic Infx of all types incl. BRAIN ABSCESSES (combine w/ another agent for aerobic orgs)
  3. Antibiotic-assoc colitis due to C. diff
  4. NO ACTIVITY AGAINST AEROBIC!
47
Q

Metronidazole Toxicities

A
  • GI upset, metallic taste
  • Central & Peripheral neuropathy (occasional)
  • Neutropenia
    4. Disulfiram-like rxn (acetaldehyde syndrome)
    5. Mutagenic in bac, possibly carcinogenic
    6. Relatively contraindicated in PREG, AVOID IN KIDS
48
Q

Nitrofurantoin Mechanism of Action

A

STATIC

-Cellular enzyme reduces drug, which then DAMAGES DNA

49
Q

Nitrofurantoin Pharmacokinetics

A
  • Rapid, excellent GI absorption
  • Rapidly met to inactive drug in many tissues
  • About 1/2 cleared into urine rapidly by glom. filtration
  • No sig levels in serum
  • SHORT 1/2 life!! (20 mins)
  • Macrocrystalline form has slower absorption, more prolonged urine levels
50
Q

Nitrofurantoin Spectrum

A

Good for E. coli…poor for others

51
Q

Nitrofurantoin Indications

A

Uncomplicated, non-severe UTI
Prophylaxis of UTI
Cannot use in systemic cases/ sepsis, only local

low cost

52
Q

Nitrofurantoin Toxicities

A

-GI upset
-Hypersensitivity (can be severe):
>Fever/chills
>Hematologic-leukopenia, hemolytic aemia
> Rashes
> Liver: cholestatic jaundice, hepatitis
> ACUTE ALLERGIC PNEUMONITIS
> SUBACUTE PULM. INTERSTITIAL FIBROSIS
> SEVERE POLYNEUROPATHIES

Pharmacology Antimicrobials (4 decks)

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