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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
What is the PK of Nitrofurantoin?
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
26
What is the effect of Nitrofurantoin on the urine?
Colours it brown
27
What are the therapeutic uses of Nitrofurantoin?
1. Useful against E.coli and Enterococci 2. Gram + cocci (S. saprophyticus) are typically susceptible 3. Recommended for lower UTIs
28
What species might be resistant to Nitrofurantoin?
Proteus Pseudomonas Many species of Enterobacter & Klebsiella
29
What UTIs is Nitrofurantoin not recommended for?
Pyelonpehritis & prostatitis
30
What are the contraindications for Nitrofurantoin?
Renal insufficiency and pregnancy
31
What are the side effects of Nitrofurantoin?
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
32
Is Fosfomycin bacteriostatic or bacteriocidal?
Bacteriocidal
33
What is Fosfomycin?
Synthetic derivative of phosphonic acid
34
What is the MOA of Fosfomycin?
1. Inhibits the enzyme UDP-N-acetylglucosamine enolpyruvul transferase (MurA) 2. Inhibit the growth of bacteria
35
What is the function of MurA?
Catalyzes the first step in peptidoglycan synthesis
36
What is the PK of Fosfomycin?
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
37
37
38
What are the therapeutic uses of Fosfomycin?
Uncomplicated UTIs caused by E. coli or E. faecalis Covers Proteus and Staphylococcus saphrophyticus
39
What is the resistance to Fosfomycin like?
Unique structure and mechanism so cross resistance with other antibiotics is unlikely
40
What are the adverse effects of Fosfomycin?
Diarrhea Vaginitis Nausea Headache
41
What are examples of Folic acid/Folate antagonists or Antifolates?
Sulfonamides Trimethoprim Co-trimoxazole
42
What is an example of Sulfonamides?
Sulfamethoxazole
43
Are Sulfanonamides bacteriostatic or bacteriocidal?
Bacteriostatic
44
What is the MOA of Sulfonamides?
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
45
What is characteristic to Sulfonamides?
Sulfonamide functional group
46
What is the PK of Sulfonamides? (4)
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
47
What are the therapeutic uses of Sulfonamides?
UTIs Otitis media Ocular infections Burns
48
What is the resistance of Sulfonamides like?
Random mutation and selection of by transfer through plasmids, laeding to reduced affinity of the drug to the enzyme, permeability barrier, efflux pump
49
What are the adverse effects of Sulfonamides? (7)
1. Anorexia 2. Nausea 3. Vomiting 4. Headaches 5. Jaundice 6. Hypersensitivity reactions (sulfa allergies) 7. Hemolytic anemia (rare)
50
Is Trimethoprim bacteriostatic or bactericidal?
Bacteriostatic
51
What is the MOA of Trimethoprim?
Interferes with pathway responsible for synthesis of DNA and RNA in bacteria
52
What is the spectrum of Trimethoprim similar to?
Sulfamethoxazole but trimethoprim is 20 to 100 fold more potent
53
What are the therapeutic uses of Trimethoprim?
UTI Bacterial prostatitis
54
What is the PK of Trimethoprim like?
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
What is the resistance of Trimethoprim like?
In gram-negative bacteria, due to an altered dihydrofolate reductase enzyme (lower affinity) Decrease in permeability
56
What are the adverse effects of Trimethoprim?
1. Effects of folic acid deficiency, especially in pregnant patients and those having poor diets --> administration of folinic acid is required
57
What are the effects of folic acid deficiency?
Megaloblastic anemia Leukopenia Granulocytopenia
58
What is co-trimoxazole?
Sulfamethoxazole & Trimethoprim
59
What is the MOA of co-trimoxazole?
Blockade of two sequential steps of THF biosynthesis Better antibacterial activity than either one alone --> due to synergy
60
What is the spectrum of co-trimoxazole like?
1. Broader spectrum than sulfa drugs alone 2. Effective in UTIs
61
What is the PK of co-trimoxazole?
1. Generally oral 2. Distributed through the body (passes the BBB) 3. Excreted in urine (both drugs and metabolites)
62
When is co-trimoxazole given IV?
In cases of severe pneumonia
63
What are the therapeutic uses of co-trimoxazole?
Prostatitis and UTI Other uses; MRSA, respiratory infections, septicaemia, meningitis, GI infections
64
What are the two penicillin-binding proteins?
Transpeptidase that cross-links amino acid side chains Glucosyltransferase that links subunits of the glycopeptide polymer
65
Are penicillins in UTI bacteriostatic or bacteriocidal?
Bacteriocidal
66
What are examples of penicillins used to treat UTIs?
Amoxicillin Ampicillin Clavulanic acid (in case of resistant organisms) Piperacillin/Tazobactam
67
What is the MOA of penicillins?
Inhibit cell wall peptidoglycan synthesis (transpeptidase enzyme)
68
What are the PK of penicillins?
Administered orally or parenterally Distributed throughout body tissues and fluid Bound mainly to albumin Eliminated via the kidney primarily by tubular secretion
69
What are the therapeutic uses of Penicillins in UTI?
Uncomplicated cases of UTIs of susceptible organisms Generally suitable in case of UTI in pregnancy
69
What are cephalosporins similar to and in what ways?
Penicillins, chemically, in MOA and toxicity
69
What is the resistance of penicillin-like?
Alteration in target (PBP) structure, efflux pumps and permeability barrier can cause resistance
69
What are the adverse effects of penicillins?
Hypersensitivity reactions to analphylaxis GI Cross sensitivity
69
What is the difference between cephalosporins and penicillins?
Cephalosporins are more stable against beta-lactamase which allows for a broad spectrum of activity
70
Are cephalosporins bacteriostatic or bacteriocidal?
Bacteriocidal
71
What are examples of cephalosporins?
Ceftriaxone Cefepime
72
What is the MOA of cephalosporins?
Similar to penicillins, inhibit cell wall peptidoglycan synthesis
73
What are the PK of cephalosporins?
P/O mostly or IV Distribute well into most body fluids Eliminated through tubular secretion and/or glomerular filtration
74
Which cephalosporin is the exception when it comes to their elimination?
Ceftriaxone, eliminated in bile and feaces
75
What are the therapeutic uses of cephalosporins?
Uncomplicated cases of UTI of susceptible organisms (PO) 3rd generation cephalosporins in complicated UTIs (Ceftriaxone, IV)
76
What is the resistance to cephalosporins like?
Mechanisms similar to penicillin; not susceptible to staphylococcal penicillinase, may be susceptible to extended spectrim beta lactamase producing enterobacteriaceae
77
What are the adverse effects of cephalosporins?
Hypersensitivity to anaphylaxis Nausea/vomiting Cross sensitivity Bleeding disorders Nephrotoxicity
77
What are examples of Fluoroquinolones?
Ciprofloxacin Norfloxacin Levoflaxacin
78
Are fluoroquinolones bacteriostatic or bactericidal?
Bactericidal
79
What is the MOA of fluoroquionolones?
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
What are the characteristics of fluoroquinolones?
Selectivity: does not affect human topoisomerase
81
What is the spectrum of fluoroquinolones like?
Broad gram - Some gram + Mycobacteria
82
What are the first-generation fluoroquinolone drugs, and what is their spectrum?
Nalidixic acid, Spectrum: gram - organisms Exception: Pseudomonas spp
83
What are the second-generation fluoroquinolone drugs, and what is their spectrum?
Ciprofloxacin Norfloxacin Ofloxacin Spectrum: improved activity against gram - (Pseudomonas spp included), some activity against gram + and atypical pathogens, aerobic
84
What are the fourth-generation fluoroquinolone drugs, and what is their spectrum?
Moxifloxacin Spectrum: increased activity against gram + organisms, broad anaerobic coverage
84
What is the resistance of fluoroquinolones like?
Altered target: mutations in bacterial genes --> reduced affinity Decreased accumulation: porin channels --> reduce Efflux pumps --> increased
85
What are the third-generation fluoroquinolone drugs, and what is their spectrum?
Levofloxacin Spectrum: same as 2nd generation & improved activity against gram + and atypical organisms
86
What are the PK of fluoroquinolones?
Orally or IV Antacids/iron/zinc can reduce absorption Most are cleared predominantly by the kidneys
87
What are the adverse effects of fluoroquinolones?
Nausea, vomiting, diarrhea, headache, dizziness and phototoxicity Possibly articular cartilage erosion/ tendon rupture!!!!!
88
What are the indications for fluoroquionolones?
Uncomplicated and complicated UTIs: pyelonephritis, and bacterial prostatitis Other uses: respiratory, skin and soft tissue, GI and into-abdominal and sexually transmitted infections
89
What are aminoglycosides used to treat?
Serious infections due to aerobic gram (-) bacilli
90
What are examples of aminoglycosides?
Gentamicin Tobramycin Streptomycin Amikacin
91
What limits the clinical utility of aminoglycosides?
Serious toxicity
92
Are aminoglycosides bacteriostatic or bactericidal?
Bactericidal
93
What is the MOA of aminoglycosides?
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
What is the PK of aminoglycosides?
Mostly IV, except for neomycin --> nephrotoxicity Mostly excreted in urine
95
What are the therapeutic uses of aminoglycosides?
effective for the majority of aerobic gram (-) bacilli, including multi-drug resistant pathogens Often combined with a beta-lactam for synergistic effect
96
What is the resistance of aminoglycosides like?
Efflux pumps, decreased uptake and/or modification and inactivation by plasmid-associated synthesis of enzymes
97
What are the adverse effects of aminoglycosides?
Ototoxicity, Nephrotoxicity Neuromuscular paralysis Allergic reactions
98
What are examples of carbapenems?
Imipenem Meropenem Ertapenem
99
What is the MOA of carbapenems?
Bacterial cell wall synthesis inhibitor
100
When are carbapenems used?
As a last resource
101
What is the spectrum of carbapenems like?
Has a broader spectrum of activity than many other beta-lactams Highly resistant to hydrolysis by beta-lactamases
102
What are the PK of carbapenems?
IV When co-administered with cilastatin, up to 70% of a dose of imipenem is excreted unchanged in the urine
103
What are the adverse effects of carbapenems?
Nausea Vomiting Diarrhea Seizures (rare)
104
What is Vancomycin?
Tricyclin glycopeptide antibiotic Produced by Streptococcus orientalis
105
Is Vancomycin bacteriostatic or bactericidal?
Bactericidal
106
What is the MOA of Vancomycin?
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
Which organisms is Vancomycin most effective towards?
Gram +
108
What is the PK of Vancomycin?
Poorly absorbed after oral administration Given slow IV Renal excretion by glomerular filtration --> drug accumulates if renal impairment --> dose adjustment
109
What are the adverse effects of Vancomycin ?
Nephrotoxicity Ototoxicity Rapid IV infusion --> erythematous or urticarial reactions --> red man syndrome Hypersensitivity reactions
110
What is Phenazopyridine?
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
What are the PK of Phenazopyridine?
Orally absorbed, Rapid excretion by kidneys directly into urine
112
What is Phenazopyridine usually combined with?
Sulfonamides
113
What are the adverse effects of Phenazopyridine?
GI upset Headache Dizziness Overdose --> methemoglobinemia
114
What are the contraindications of Phenazopyridine?
Renal insufficiency Liver disease G6PD deficiency
115
What is the treatment of UTIs in pregnant women like?
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
What is the treatment of UTIs in patients with renal impairment like?
1. Use aminoglycosides with great caution 2. Methanamine and nitrofurantoin must be avoided
117
What is the first-line treatment for uncomplicated UTIs?
Nitrofurantoin Fosfomycin Pivmecillinam
118
What is the second-line treatment for uncomplicated UTIs?
Cephalosporins
119
What are alternative regimens for uncomplicated UTIs?
If local resistance for E. coli is < 20% include trimethoprim/sulfamethoxazole
120
What is the symptomatic treatment for uncomplicated UTIs?
NSAIDs and analgesics
121
Which antibiotics are not recommended for uncomplicated UTIs?
Fluoroquinolones Aminopenicillins
122
What is the first-line treatment for uncomplicated pyelonephritis?
Oral: cephalosporins, trimethoprim-sulfamethoxazole, fluoroquinolones IV: for patients who require hospitalization Cephalosporins, fluoroquinolones
123
What is the second-line treatment for uncomplicated pyelonephritis?
Beta-lactams and aminoglycosides
124
What are the recommended regimen for complicated UTIs?
Amoxicillin & aminoglycoside A 2nd generation cephalosporin & aminoglycoside A 3rd generation cephalosporin IV as empiric treatment of a complicated UTI with systemic symptoms
125
When is ciprofloxacin recommended in the treatment of complicated UTIs?
If local resistance is < 10%
126
Which antibiotics are not recommended for the treatment of pyelonephritis?
Nitrofurantoin Oral fosfomycin Pivmecillinam
127

Renal System (24 decks)

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