PHARMACOLOGY

Case Management - GROUP 11

Atienza, Joseph Rigo M. San Buenaventura, Maria Phoebe J.

Bagsit, Bienelle B. Tagra, Mine C.
Bertos, Aron Glenn A. Tiburcio, Marianne Cyril H.
Galano, Rhealyn Mae C. Umali, Christine H.
Garcia, Gielen Nikki Q. Vila, Kathleen Kay O.
Morte, Maria Ysabel T.

Case 1: URINARY TRACT INFECTION

1. What signs and symptoms of an uncomplicated UTI does the patient have?
● Commonly seen in the young - patient is 18 years old
● Sexually active
● Dysuria
● Urinary frequency
● Suprapubic pain/ tenderness

2. What risk factors does the patient have for uncomplicated UTIs?
● Risk factors:
○ Shorter urethra of female
○ non-Pregnant,
○ no known structural or functional abnormalities
○ history of sexual intercourse
○ variety of virulence factors are present
○ smoking history of the patient

3. What are the treatment goals?

● For our patient, the goal is to treat the symptoms of uncomplicated UTI which
are dysuria, urgency and frequency and also to eradicate the organism causing
the infection. We have to provide the suitable antibiotic for the patient by
determining the agent through urine culture. Proper antibiotic treatment will also
prevent the early recurrence of UTI with the same organism.
● To prevent the recurrence of UTI, it is also recommended that our patient who is
sexually active to do post coital urination and post coital washing.

4. If any, which antibiotic treatment options including duration of therapy should be

considered in this patient?
● Empiric antibiotics should be given such as Nitrofurantoin macrocrystal 100 mg to
be given 4 times a day for 5 days PO or Fosfomycin trometamol 3g given as a
single dose.
 5. If any, which antifungal treatment options including duration of therapy should be
considered in this patient?
● Fluconazole 200mg/day for 7-14 days
● If resistance to fluconazole is suspected, bladder irrigation with amphotericin B at
a dose of 0.3-1.0 mg/kg per day for 1-7 days is recommended.
● For organisms resistant to amphotericin B, sometimes Flucytosine is added
which may be given orally 50-150 mg/kg/day in 4 divided doses or intravenously
200 mg/kg/day in 4 divided doses; given with amphotericin B or fluconazole

6. What risk and adverse effects of therapy should be discussed with this patient?
● Antibiotic therapy
○ The patient may experience nausea, anorexia, vomiting, abdominal pain,
diarrhea, headache, pseudomembranous colitis, exfoliative dermatitis,
erythema multiforme (including Stevens-Johnson syndrome),
maculopapular rash, rash erythematous. The patient should also be
advised that there will be discoloration of urine and may cause false
positive in the urine test for glucose.

● Antifungal therapy
○ Patient may experience nausea, vomiting, diarrhea, upset stomach,
headache, dizziness, hair loss. The patient is at risk for liver disease
when overdose occur.

A previous culture showed Escherichia coli and she responded well to the combination of
TMP-SMX. After obtaining the appropriate cultures and sensitivities, you decide to treat her
again with this combination.

7. What is unique about the mechanism of action of this combination that make it effective
in treating bacterial infections?
● The combination of Trimethoprim - Sulfamethoxazole makes a synergistic effect
in interfering with the bacterial folic acid synthesis which is necessary for the
survival of the bacteria. This works with the Sulfonamides inhibiting the bacterial
synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA)
via inhibiting dihydropteroate synthase; and Trimethoprim works by blocking the
tetrahydrofolate acid production by inhibiting dihydrofolate reductase.

8. Since both combinations affects folate synthesis, does it induce folate deficiency in
humans? Of what untoward effects should this patient be warned?
● As was mentioned earlier, the mechanism is to inhibit the folate synthesis and a
direct competitor of dihydrofolate reductase. In a normal person, giving a
recommended dose of this drug won't’ have any effect on human cells instead it
would affect only the bacteria. However in an individual who has a folate
 deficiency, even at the recommended dose, it may be toxic to humans. It may
precipitate some reactions on diseases like megaloblastosis, leukopenia, or
thrombocytopenia. (​Reference: Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor
(eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th
ed. New York, NY. Pergamon Press, 1990., p. 1055)

If the patient is treated with Ciprofloxacin, but a repeat culture shows that the organism is now
resistant.

9. What is the mechanism of action of the quinolones?

● Quinolones interfere with bacterial DNA unwinding and replicating via
○ Inhibiting topoisomerase II (DNA gyrase) - prevents relaxation of DNA
supercoiling required for replication
○ Inhibiting topoisomerase IV - prevents separation of bacterial DNA after
replication during cell division

10. How does resistance develop in quinolones?

● Resistance to Quinolones develop through mutations in one or both of the target
enzymes: DNA gyrase and DNA topoisomerase IV
● Both can be seen in the localized domain of the GyrA and ParE subunits of each
enzyme and reduce drug binding to the enzyme-DNA complex
● Other resistance mutations can happen in regulatory genes that controls the
expression of native efflux pumps localized in the bacterial membrane

Patient is now treated with nitrofurantoin chronically to suppress E. coli which has been the
organism most commonly cultured for her urinary tract.

11. What kind of drug is nitrofurantoin and what is its mechanism of action?
● it is a bacteriostatic drug but can be bactericidal in high dose.
● MOA: It interferes with carbohydrate metabolism of the organism by inhibiting
bacterial acetyl coenzyme-A inhibitor. protein synthesis, aerobic energy
metabolism, DNA, RNA, and bacterial cell wall synthesis.

12. What are the common untoward effects of nitrofurantoin?

● The most common untoward effects of Nitrofurantion (1% to 10%) includes
headache, increased serum phosphatase, nausea, flatulence, decreased
hemoglobin, eosinophilia, increased serum alanine transferase, and increased
serum aspartate aminotransferase.

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