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Renal System > Pharmacotherapy of UTI > Flashcards

Pharmacotherapy of UTI Flashcards

1
Q

What are UTIs?

A

Infections of the upper or lower urinary tract, usually caused by bacteria

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2
Q

What are the common symptoms of UTIs? (7)

A

Can range depending on the site of infection:
1. Burning sensation during urination
2. Discharge to pelvic pressure
3. Lower abdomen discomfort
4. Frequent, painful urination
5. Hematuria
6. Upper back and side pain (pyelonephritis)
7. High fever (pyelonephritis)

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3
Q

What are the common pathogens that cause UTIs? (8)

A
  1. E. coli
  2. Staphylococcus sacrophyticus
  3. Proetus
  4. Klebsiella spp
  5. Pseudomonas
  6. Staphylococcus epidermidis
  7. Enterococcus faecalis
  8. Candida
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4
Q

What are the goals of the pharmacotherapy in UTI? (3)

A
  1. Eradicate the pathogen
  2. Prevent recurrence
  3. Symptomatic relief
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5
Q

What are examples of Urinary antiseptics?

A

Methenamine
Nitrofurantoin
Nalidixic acid

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6
Q

What is the purpose of Urinary antiseptics?

A

They concentrate mainly in the renal tubules –> inhibit growth of bacteria

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7
Q

What is a requirement of urinary antiseptics before presecribing?

A

Acidic urine

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8
Q

How are urinary antiseptics administered?

A

Orally

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9
Q

What are the therapeutic purposes of urinary antiseptics?

A

Mainly useful for lower UTIs
Not useful to treat systemic infections, effective concentrations not achieved in plasma with safe dose

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10
Q

What is Methenamine?

A

It is a prodrug, it decomposes in acidic urine to produce Formaldehyde, which is toxic to bacteria

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11
Q

What is the resistance to Methenamine like?

A

No resistance development

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12
Q

What is Methenamine usually administered with and why?

A

Generally given with a weak acid (mandelic/hippuric acid) in order to acidify the urine and have the best effect

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13
Q

Is Methenamine a bacteriostatic or bacteriocidal?

A

Bacteriostatic

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14
Q

What are the PK of Methenamine?

A

Orally taken
Contraindicated in hepatic insufficiency as ammonia can accumulate
Excreted in urine

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15
Q

How is ammonia related to Methenamine?

A

When Methenamine is converted to 6-Formaldehyde, ammonia is also released

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16
Q

What are the therapeutic uses of Methenamine?

A
  1. Chronic suppression therapy in recurrent UTI
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17
Q

When is Methenamine not advised?

A
  1. Not recommended in chronic catheterization-associated UTI
  2. Not recommended in upper UTI
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18
Q

Which kind of bacteria are resistant to Methenamine?

A

Bacteria that alkaline urine, like Proteus spp.

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19
Q

What are the side effects of Methenamine? (3)

A
  1. GI distress
  2. At high doses: hematuria, albuminuria, rashes
  3. Crystalluria
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20
Q

How is crystalluria a side effect of Methenamine?

A

Sulfonamides should not be used along with methenamine as they react and cause crystalluria

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21
Q

What is a contraindication of Methenamine?

A

Renal insufficiency

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22
Q

What is the mechanism of action of Nitrofurantoin?

A
  1. Enzymatic reduction by nitrofurantoin reductase in sensitive bacteria
  2. Formation of highly reactive intermediates
  3. Inhibition of various enzymes and damages ribosomal RNA, bacterial DNA, and other intracellular components
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23
Q

Is Nitrofurantoin bacteriostatic or bacteriocidal?

A

It can be both; bacteriostatic at ≤32μg/mL and bacteriocidal > 100μg/mL

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24
Q

What affects the activity of Nitrofurantoin?

A

pH, higher activity in acidic pH

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25
Q

What is the PK of Nitrofurantoin?

A
  1. Given orally; rapidly and totally absorbed from GIT
  2. Rapidly excreted by kidneys (40% unchanged in urine)
  3. Impaired glomerular function reduces excretion and increases plasma levels –> toxicity
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26
Q

What is the effect of Nitrofurantoin on the urine?

A

Colours it brown

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27
Q

What are the therapeutic uses of Nitrofurantoin?

A
  1. Useful against E.coli and Enterococci
  2. Gram + cocci (S. saprophyticus) are typically susceptible
  3. Recommended for lower UTIs
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28
Q

What species might be resistant to Nitrofurantoin?

A

Proteus
Pseudomonas
Many species of Enterobacter & Klebsiella

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29
Q

What UTIs is Nitrofurantoin not recommended for?

A

Pyelonpehritis & prostatitis

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30
Q

What are the contraindications for Nitrofurantoin?

A

Renal insufficiency and pregnancy

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31
Q

What are the side effects of Nitrofurantoin?

A
  1. GI disturbances, hypersensitivity reactions, acute pneumonitis, interstitial pulmonary fibrosis
  2. Higher risk for hemolytic anemia in those with G6PD deficiency, leukopenia and granulocytopenia
  3. Hepatotoxicity and neurologic problems (peripheral neuropathy)
  4. Headache, vertigo, drowsiness, muscular aches, nystagmus
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32
Q

Is Fosfomycin bacteriostatic or bacteriocidal?

A

Bacteriocidal

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33
Q

What is Fosfomycin?

A

Synthetic derivative of phosphonic acid

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34
Q

What is the MOA of Fosfomycin?

A
  1. Inhibits the enzyme UDP-N-acetylglucosamine enolpyruvul transferase (MurA)
  2. Inhibit the growth of bacteria
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35
Q

What is the function of MurA?

A

Catalyzes the first step in peptidoglycan synthesis

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36
Q

What is the PK of Fosfomycin?

A

Rapidly absorbed orally
Excreted in urine and feaces in its active form
High concentrations in urine are maintained over several days –> one-time-dose for UTI

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37
Q
A
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37
Q
A
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38
Q

What are the therapeutic uses of Fosfomycin?

A

Uncomplicated UTIs caused by E. coli or E. faecalis
Covers Proteus and Staphylococcus saphrophyticus

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39
Q

What is the resistance to Fosfomycin like?

A

Unique structure and mechanism so cross resistance with other antibiotics is unlikely

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40
Q

What are the adverse effects of Fosfomycin?

A

Diarrhea
Vaginitis
Nausea
Headache

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41
Q

What are examples of Folic acid/Folate antagonists or Antifolates?

A

Sulfonamides
Trimethoprim
Co-trimoxazole

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42
Q

What is an example of Sulfonamides?

A

Sulfamethoxazole

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43
Q

Are Sulfanonamides bacteriostatic or bacteriocidal?

A

Bacteriostatic

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44
Q

What is the MOA of Sulfonamides?

A

They are competitive inhibitors of dihydropteroate synthase enzyme
They interfere with the pathway responsible for the synthesis of folic acid and, thereby, nucleic acid synthesis in bacteria

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45
Q

What is characteristic to Sulfonamides?

A

Sulfonamide functional group

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46
Q

What is the PK of Sulfonamides? (4)

A
  1. Rapidly absorbed after oral administration
  2. Bind to plasma proteins; distributed into most body tissues and fluids
  3. Metabolized by the liver
  4. Excreted in unchanged and metabolized form through the kidneys
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47
Q

What are the therapeutic uses of Sulfonamides?

A

UTIs
Otitis media
Ocular infections
Burns

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48
Q

What is the resistance of Sulfonamides like?

A

Random mutation and selection of by transfer through plasmids, laeding to reduced affinity of the drug to the enzyme, permeability barrier, efflux pump

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49
Q

What are the adverse effects of Sulfonamides? (7)

A
  1. Anorexia
  2. Nausea
  3. Vomiting
  4. Headaches
  5. Jaundice
  6. Hypersensitivity reactions (sulfa allergies)
  7. Hemolytic anemia (rare)
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50
Q

Is Trimethoprim bacteriostatic or bactericidal?

A

Bacteriostatic

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51
Q

What is the MOA of Trimethoprim?

A

Interferes with pathway responsible for synthesis of DNA and RNA in bacteria

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52
Q

What is the spectrum of Trimethoprim similar to?

A

Sulfamethoxazole but trimethoprim is 20 to 100 fold more potent

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53
Q

What are the therapeutic uses of Trimethoprim?

A

UTI
Bacterial prostatitis

54
Q

What is the PK of Trimethoprim like?

A

Rapidly absorbed following oral administration
Reaches a higher concentration in relatively acidic prostatic and vaginal fluids
Widely distributed into body tissues and fluids
60 to 80% is excreted unchanged via kidneys

55
Q

What is the resistance of Trimethoprim like?

A

In gram-negative bacteria, due to an altered dihydrofolate reductase enzyme (lower affinity)
Decrease in permeability

56
Q

What are the adverse effects of Trimethoprim?

A
  1. Effects of folic acid deficiency, especially in pregnant patients and those having poor diets –> administration of folinic acid is required
57
Q

What are the effects of folic acid deficiency?

A

Megaloblastic anemia
Leukopenia
Granulocytopenia

58
Q

What is co-trimoxazole?

A

Sulfamethoxazole & Trimethoprim

59
Q

What is the MOA of co-trimoxazole?

A

Blockade of two sequential steps of THF biosynthesis
Better antibacterial activity than either one alone –> due to synergy

60
Q

What is the spectrum of co-trimoxazole like?

A
  1. Broader spectrum than sulfa drugs alone
  2. Effective in UTIs
61
Q

What is the PK of co-trimoxazole?

A
  1. Generally oral
  2. Distributed through the body (passes the BBB)
  3. Excreted in urine (both drugs and metabolites)
62
Q

When is co-trimoxazole given IV?

A

In cases of severe pneumonia

63
Q

What are the therapeutic uses of co-trimoxazole?

A

Prostatitis and UTI
Other uses; MRSA, respiratory infections, septicaemia, meningitis, GI infections

64
Q

What are the two penicillin-binding proteins?

A

Transpeptidase that cross-links amino acid side chains
Glucosyltransferase that links subunits of the glycopeptide polymer

65
Q

Are penicillins in UTI bacteriostatic or bacteriocidal?

A

Bacteriocidal

66
Q

What are examples of penicillins used to treat UTIs?

A

Amoxicillin
Ampicillin
Clavulanic acid (in case of resistant organisms)
Piperacillin/Tazobactam

67
Q

What is the MOA of penicillins?

A

Inhibit cell wall peptidoglycan synthesis (transpeptidase enzyme)

68
Q

What are the PK of penicillins?

A

Administered orally or parenterally
Distributed throughout body tissues and fluid
Bound mainly to albumin
Eliminated via the kidney primarily by tubular secretion

69
Q

What are the therapeutic uses of Penicillins in UTI?

A

Uncomplicated cases of UTIs of susceptible organisms
Generally suitable in case of UTI in pregnancy

69
Q

What are cephalosporins similar to and in what ways?

A

Penicillins, chemically, in MOA and toxicity

69
Q

What is the resistance of penicillin-like?

A

Alteration in target (PBP) structure, efflux pumps and permeability barrier can cause resistance

69
Q

What are the adverse effects of penicillins?

A

Hypersensitivity reactions to analphylaxis
GI
Cross sensitivity

69
Q

What is the difference between cephalosporins and penicillins?

A

Cephalosporins are more stable against beta-lactamase which allows for a broad spectrum of activity

70
Q

Are cephalosporins bacteriostatic or bacteriocidal?

A

Bacteriocidal

71
Q

What are examples of cephalosporins?

A

Ceftriaxone
Cefepime

72
Q

What is the MOA of cephalosporins?

A

Similar to penicillins, inhibit cell wall peptidoglycan synthesis

73
Q

What are the PK of cephalosporins?

A

P/O mostly or IV
Distribute well into most body fluids
Eliminated through tubular secretion and/or glomerular filtration

74
Q

Which cephalosporin is the exception when it comes to their elimination?

A

Ceftriaxone, eliminated in bile and feaces

75
Q

What are the therapeutic uses of cephalosporins?

A

Uncomplicated cases of UTI of susceptible organisms (PO)
3rd generation cephalosporins in complicated UTIs (Ceftriaxone, IV)

76
Q

What is the resistance to cephalosporins like?

A

Mechanisms similar to penicillin; not susceptible to staphylococcal penicillinase, may be susceptible to extended spectrim beta lactamase producing enterobacteriaceae

77
Q

What are the adverse effects of cephalosporins?

A

Hypersensitivity to anaphylaxis
Nausea/vomiting
Cross sensitivity
Bleeding disorders
Nephrotoxicity

77
Q

What are examples of Fluoroquinolones?

A

Ciprofloxacin
Norfloxacin
Levoflaxacin

78
Q

Are fluoroquinolones bacteriostatic or bactericidal?

A

Bactericidal

79
Q

What is the MOA of fluoroquionolones?

A

Enter the bacterium by passive diffusion through porins in the outer membrane
Inhibit DNA gyrase (topoisomerase II) & topoisomerase IV
Inhibit replication of DNA
Bacterial cell death

80
Q

What are the characteristics of fluoroquinolones?

A

Selectivity: does not affect human topoisomerase

81
Q

What is the spectrum of fluoroquinolones like?

A

Broad gram -
Some gram +
Mycobacteria

82
Q

What are the first-generation fluoroquinolone drugs, and what is their spectrum?

A

Nalidixic acid,
Spectrum: gram - organisms
Exception: Pseudomonas spp

83
Q

What are the second-generation fluoroquinolone drugs, and what is their spectrum?

A

Ciprofloxacin
Norfloxacin
Ofloxacin

Spectrum: improved activity against gram - (Pseudomonas spp included), some activity against gram + and atypical pathogens, aerobic

84
Q

What are the fourth-generation fluoroquinolone drugs, and what is their spectrum?

A

Moxifloxacin
Spectrum: increased activity against gram + organisms, broad anaerobic coverage

84
Q

What is the resistance of fluoroquinolones like?

A

Altered target: mutations in bacterial genes –> reduced affinity

Decreased accumulation: porin channels –> reduce
Efflux pumps –> increased

85
Q

What are the third-generation fluoroquinolone drugs, and what is their spectrum?

A

Levofloxacin
Spectrum: same as 2nd generation & improved activity against gram + and atypical organisms

86
Q

What are the PK of fluoroquinolones?

A

Orally or IV
Antacids/iron/zinc can reduce absorption
Most are cleared predominantly by the kidneys

87
Q

What are the adverse effects of fluoroquinolones?

A

Nausea, vomiting, diarrhea, headache, dizziness and phototoxicity
Possibly articular cartilage erosion/ tendon rupture!!!!!

88
Q

What are the indications for fluoroquionolones?

A

Uncomplicated and complicated UTIs: pyelonephritis, and bacterial prostatitis

Other uses: respiratory, skin and soft tissue, GI and into-abdominal and sexually transmitted infections

89
Q

What are aminoglycosides used to treat?

A

Serious infections due to aerobic gram (-) bacilli

90
Q

What are examples of aminoglycosides?

A

Gentamicin
Tobramycin
Streptomycin
Amikacin

91
Q

What limits the clinical utility of aminoglycosides?

A

Serious toxicity

92
Q

Are aminoglycosides bacteriostatic or bactericidal?

A

Bactericidal

93
Q

What is the MOA of aminoglycosides?

A

Inhibit bacterial protein synthesis: bind to 30s ribosomes inside the cell, interfere with the assembly of the functional ribosomal apparatus, and/or cause the 30S subunit of the completed ribosome to misread the genetic code

94
Q

What is the PK of aminoglycosides?

A

Mostly IV, except for neomycin –> nephrotoxicity
Mostly excreted in urine

95
Q

What are the therapeutic uses of aminoglycosides?

A

effective for the majority of aerobic gram (-) bacilli, including multi-drug resistant pathogens

Often combined with a beta-lactam for synergistic effect

96
Q

What is the resistance of aminoglycosides like?

A

Efflux pumps, decreased uptake and/or modification and inactivation by plasmid-associated synthesis of enzymes

97
Q

What are the adverse effects of aminoglycosides?

A

Ototoxicity,
Nephrotoxicity
Neuromuscular paralysis
Allergic reactions

98
Q

What are examples of carbapenems?

A

Imipenem
Meropenem
Ertapenem

99
Q

What is the MOA of carbapenems?

A

Bacterial cell wall synthesis inhibitor

100
Q

When are carbapenems used?

A

As a last resource

101
Q

What is the spectrum of carbapenems like?

A

Has a broader spectrum of activity than many other beta-lactams
Highly resistant to hydrolysis by beta-lactamases

102
Q

What are the PK of carbapenems?

A

IV
When co-administered with cilastatin, up to 70% of a dose of imipenem is excreted unchanged in the urine

103
Q

What are the adverse effects of carbapenems?

A

Nausea
Vomiting
Diarrhea
Seizures (rare)

104
Q

What is Vancomycin?

A

Tricyclin glycopeptide antibiotic
Produced by Streptococcus orientalis

105
Q

Is Vancomycin bacteriostatic or bactericidal?

A

Bactericidal

106
Q

What is the MOA of Vancomycin?

A

High affinity binding to the d-alanyl-d-alanine terminus of peptidoglycan precursors –> prevents transpeptidase action on NAM & NAG –> disrupts polymerization and cross linking

It also inhibits transglycolase

107
Q

Which organisms is Vancomycin most effective towards?

A

Gram +

108
Q

What is the PK of Vancomycin?

A

Poorly absorbed after oral administration
Given slow IV
Renal excretion by glomerular filtration –> drug accumulates if renal impairment –> dose adjustment

109
Q

What are the adverse effects of Vancomycin ?

A

Nephrotoxicity
Ototoxicity
Rapid IV infusion –> erythematous or urticarial reactions –> red man syndrome
Hypersensitivity reactions

110
Q

What is Phenazopyridine?

A

Not a urinary antiseptic
It has an analgesic action on the urinary tract
Alleviates symptoms of dysuria, burning, and urgency
COlours the urine orange/red

111
Q

What are the PK of Phenazopyridine?

A

Orally absorbed,
Rapid excretion by kidneys directly into urine

112
Q

What is Phenazopyridine usually combined with?

A

Sulfonamides

113
Q

What are the adverse effects of Phenazopyridine?

A

GI upset
Headache
Dizziness
Overdose –> methemoglobinemia

114
Q

What are the contraindications of Phenazopyridine?

A

Renal insufficiency
Liver disease
G6PD deficiency

115
Q

What is the treatment of UTIs in pregnant women like?

A
  1. May be asymptomatic and requires prompt treatment to avoid complications
  2. Penicillins and cephalosporins ae suitable
  3. Sulfonamides and trimethoprim must be avoided
  4. Nitrofurantoin may be used –> should be avoided at term
116
Q

What is the treatment of UTIs in patients with renal impairment like?

A
  1. Use aminoglycosides with great caution
  2. Methanamine and nitrofurantoin must be avoided
117
Q

What is the first-line treatment for uncomplicated UTIs?

A

Nitrofurantoin
Fosfomycin
Pivmecillinam

118
Q

What is the second-line treatment for uncomplicated UTIs?

A

Cephalosporins

119
Q

What are alternative regimens for uncomplicated UTIs?

A

If local resistance for E. coli is < 20% include trimethoprim/sulfamethoxazole

120
Q

What is the symptomatic treatment for uncomplicated UTIs?

A

NSAIDs and analgesics

121
Q

Which antibiotics are not recommended for uncomplicated UTIs?

A

Fluoroquinolones
Aminopenicillins

122
Q

What is the first-line treatment for uncomplicated pyelonephritis?

A

Oral: cephalosporins, trimethoprim-sulfamethoxazole, fluoroquinolones

IV: for patients who require hospitalization
Cephalosporins, fluoroquinolones

123
Q

What is the second-line treatment for uncomplicated pyelonephritis?

A

Beta-lactams and aminoglycosides

124
Q

What are the recommended regimen for complicated UTIs?

A

Amoxicillin & aminoglycoside
A 2nd generation cephalosporin & aminoglycoside
A 3rd generation cephalosporin IV as empiric treatment of a complicated UTI with systemic symptoms

125
Q

When is ciprofloxacin recommended in the treatment of complicated UTIs?

A

If local resistance is < 10%

126
Q

Which antibiotics are not recommended for the treatment of pyelonephritis?

A

Nitrofurantoin
Oral fosfomycin
Pivmecillinam

127
Q
A

Renal System (24 decks)

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