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Pharmacology Exam 2 > Fluoroquinolones and Drugs for UTI > Flashcards

Fluoroquinolones and Drugs for UTI Flashcards

1
Q

Fluoroquinolone Drugs

A 
Ciprofloxacin
Ofloxacin
Levofloxacin
Moxifloxacin
Gatifloxacin
Gemifloxacin
"COLe Might Get Goals"
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2
Q

Fluoroquinolone MOA

A

Inhibition of DNA GYRASE (main target) - prevents relaxation of supercoiled DNA for transcription/replication
BACTERICIDAL

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3
Q

Fluoroquinolone Spectrum

A

Aerobic G- rods
Good G+ coverage
Exception: Moxifloxacin and Gemifloxacin are effective against ANAEROBES

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4
Q

Fluroquinolones effective against anaerobes

A

Moxifloxacin and Gemifloxacin

Only fluoroquinolones with “m” in the name

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5
Q

Ciprofloxacin Use

A

UTIs (2nd line, Bactrim is DOC), ANTHRAX prophylaxis, P. aeruginosa, systemic infections

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6
Q

Ofloxacin Use

A

PROSTATITIS, STDs (except syphilis), TB

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7
Q

Levofloxacin Use

A

CAP alternative (Macrolide is DOC)

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8
Q

CAP treatment

A

Macrolide (DOC) > Levofloxacin (or Gemifloxacin) > Telithromycin (has severe hepatotoxicity)

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9
Q

Moxifloxacin

A

PCN-resistant S. pneumoniae

ANAEROBES

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10
Q

Gatifloxacin

A

OCULAR application only

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11
Q

Gemifloxacin

A

PCN-resistant S. pneumonia
ANAEROBES
CAP alternative (Macrolide is DOC)

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12
Q

Fluoroquinolone Pharmacokinetics

A

Well absorbed ORALLY
Decreased absorption with CA, Mg, Al (antacids)
Widely distributed, EXCELLENT TISSUE PENETRATION
Poor CNS penetration
Excreted through kidney (can be blocked by probenecid)

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13
Q

Fluoroquinolone Adverse Effects

A 
GI disturbances
QT PROLONGATION
Cartilage erosions
Tendon rupture (more likely in men >50 w/ previous use of inhaled corticosteroids)
Photosensitivity
etc...
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14
Q

Fluoroquinolone Contraindication

A

Pregnant
Nursing
Children <18 years old (cartilage damage)

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15
Q

Fluoroquinolone Resistance

A

Plasmid mediated resistance:
Target site mutations (DNA gyrase/topoisomerase IV)
Reduced permeability
MDR efflux pump over-expression

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16
Q

What is a prodrug?

A

Drug that must be metabolized or altered to be effective

17
Q

Antibiotics that are prodrugs

A

METRONIDAZOLE - non-enzymatically reduced by reacting with reduced ferredoxin (only in anaerobes).
NITROFURANTOIN - reduced in bacterial cells to a highly reactive intemediate
METHENAMINE - decomposes to formaldehyde and ammonia in the acid medium of the urinary tract

18
Q

Metronidazole Spectrum

A

ANAEROBES only! (G- and G+ bacilli)

19
Q

Metronidazole Uses

A 
Indicated for anaerobic or mixed intra-abdominal infections
VAGINITIS (bacterial vaginosis)
C diff (DOC, also oral vancomycin)
Endocarditis
RTI (respiratory tract infection)
H. pylori therapy (multi drug regimen)
20
Q

Metronidazole Administration

A

Oral, IV, or topical

21
Q

Metronidazole Metabolism

A

Liver metabolism

Eliminated in the urine

22
Q

Metronidazole Adverse Reactions

A 
DISULFIRAM-LIKE RXN
Disgeusia (Metallic taste)
GI disturbances
Central and peripheral nervous system toxicity: seizures and peripheral neuropathy with prolonged use
Hypersensitivity
23
Q

Exclusive UTI Drugs

A

Nitrofurantoin

Methenamine

24
Q

UTI Common Pathogens

A

E. coli (most community acquired infections: 70-80%)
Staph saprophyticus, G+ organism causes 10-15%
Proteus, Klebsiella, Seratia, Pseudomonas (G- from catheter-associated UTIs)

25
Q

Why are nitrofurantoin and methenamine good for UTIs?

A

Renally excreted (where infection is)

Concentration-dependent cidal activity:
Achieve high urinary concentrations
Bactericidal activity in the urine (do NOT achieve therapeutic concentrations anywhere else in body)

26
Q

Nitrofurantoin MOA

A

Reduced to highly reactive intermediate in bacterial cells to attack ribosomes, DNA, metabolism, and other macromolecules (PRODRUG)

27
Q

Nitrofurantoin Spectrum

A

WIDE Spectrum against G+ and G-: E. coli, S. pyogenes, Citrobacter, Klebsiella, Enterobacter, Salmonella, Shigella, Serratia, and indole positive Proteus
Most PROTEUS and PSEUDOMONAS organisms are resistant!

28
Q

Nitrofurantoin Use

A

Alternative uncomplicated UTI treatment (E. coli resistant to Bactrim and Fluoroquinolones)

29
Q

Uncomplicated UTI Treatment

A

Bactrim > Fluoroquinolones > Nitrofurantoin

30
Q

Nitrofurantoin Pharmacokinetics

A

Rapid and complete oral absorption
Acidic urine (pH<5.5) increases therapeutic action
Activity decreased when glomerular filtration impaired - can’t get to site of action.

31
Q

Nitrofurantoin Contraindication

A

Creatinine clearance is less than 50 mL/min
Impaired renal function (abx can’t get to site of infection)
End of term Pregnancy (don’t know babies G6PD status)
<1 month of age
Allergy

32
Q

Nitrofurantoin Adverse Effects

A

Colors the urine brown! (normal, but tell patient)
GI upset
Allergic reactions
HEMOLYTIC ANEMIA and hepatocellular damage in G6PD deficiency
Pulmonary fibrosis with chronic usage
Neurological disorders (demyelination and degeneration of neurons)

33
Q

Methenamine MOA

A

Decomposes to formaldehyde and ammonia in the acid medium of the urinary tract –> Must be in ACIDIC environment to work.

34
Q

Methenamine Administration

A

Oral. Well absorbed orally but some decomposition occurs in the stomach.

35
Q

Methenamine Resistance

A

NONE!!! Only drug with no resistance.

Bacterial resistance to formaldehyde does not develop.

36
Q

Methenamine Spectrum

A

Nearly all bacteria are SENSITIVE, but those that increase the pH of the urine inhibit the release of formaldehyde.
Therefore, PROTEUS is resistant - should combine with a weak organic acid (hippuric acid)

37
Q

Methenamine Toxicity

A

Essentially NON-TOXIC b/c little decomposition takes place until it is in the acidic urine.
May cause GI distress
Occasional Allergic Rxns

38
Q

Methenamine Contraindications

A

Hepatic insufficiency - Liver can’t deal with ammonia

Renal insufficiency - Can’t get to site of infection

Pharmacology Exam 2 (4 decks)

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