Download Case 18 - Caangay

Clinical Case 18
Presenter: LIN,HUEI-HSIU(Caroline)
LIN,I-CHEN(Tina)
Pharmacology A
October/5th, 2006
Case 18
J.V., a 23 y/o female, single was
seen at the OPD because of
dysuria, frequency, urgency and
suprapubic pain.
Urinalysis revealed UTI.
(Urinary tract infection)
1) What antimicrobial combination could be
given?
2) State the drug interaction exhibited and
the mechanism of action.
3) What alternative drug can be given?
4) Mode of action of the alternative drug.
5) Adverse effects of the alternative drug.
Urinary tract infection
 UTI (most commonly uncomplicated acute
cystitis and pyleonephritis )in women of child
bearing age and in the elderly are one of the
most common problems seen by primary care
physicians
 Escherichia coli is the most common pathogen,
causing about 8percent of uncomplicated upper
and lower UTIs
 Staphylococcus saprophyticus is the second
most common bacterial pathogen causing UTIs
with other common cause including Klebsiella
pneumoniae and Proteus mirabilis
1.What antimicrobial combination could
be given?
Bladder infections, kidney infections, and other
urinary tract infections are often treated with
antibacterial drugs.
The type of drug used and the duration of treatment
depend on the type of bacteria.
Most UTIs are treated with :
-trimethoprim-sulfamethoxazole (e.g., Bactrim®,
Cotrim®, Septra®)
The infection may improve within a couple of days,
but 1 to 2 weeks of medication may be prescribed to
prevent a kidney infection.
2.State the drug interaction exhibited and
the mechanism of action.
 The synergistic antimicrobial activity of cotrimoxazole (TMP/SMX) results from its inhibition of
two sequential steps in the synthesis of
tetrahydrofolic acid :
 sulfamethoxazole inhibits the incorporation of PABA
into folic acid
 trimethoprim prevents reduction of dihydrofolate to
tetrahydrofolate
Adverse effect
 Dermatologist : reactions involving the skin are very
common and may be severe in the elderly
 Gastrointestinal : nausea,vomiting ,as well as
glossitis and stomatitis are not unusual
 Hematologic : megaloblastic anemia, leukopenia and
thrombocytopenia may occur. All these effects may be
reversed by the concurrent administration of folinic
acid ,which protects the patient and does not enter the
microorganism. Hemolytic anemia may occur in
patients with glucose 6-phosphate dehydrogenase
deficiency due to the sulfamethoxazole
3) What alternative drug can be given?
4) Mode of action of the alternative drug.
5) Adverse effects of the alternative drug.
 Question 3, 4, 5 - We combine together
to discuss.
Quinolones, Folate antagonists, and
urinary tract antiseptics
A. Fluoroquinolone
B. Inhibitors of Folate Synthesis
C. Inhibitors of Folate Reduction
D. Combination of Inhibitors of Folate and
Reduction (TMP/SMX)
E. Urinary tract Antiseptics
A. Fluoroquinolone
First
generation
Second
generation
Third
generation
Fourth
generation
Nalidixic acid Ciprofloxacin Gatifloxacin Trovafloxacin
Norfloxacin
Levofloxacin
Ofloxacin
Moxifloxacin
Sparfloxacin
UTI often use Second generation….
Fluoroquinolone : mechanism
The fluoroquinolone enter the bacterium
by passive diffusion through water-filled
protein channels (porins) in the outer
membrane.
Once inside the cell inhibit the replication
of bacterial DNA by interfering with the
action of DNA gyrase (Topoisomerase II)
during bacterial growth and reproduction.
Fluoroquinolone : adverse effects
 Gastrointestinal (most common): Nausea,
Vomiting and Diarrhea
 Headache
 Dizziness
 Nephrotoxicity
 Phototoxicity : Patient are advised to avoid
excessive sunlight (drug should be discontinued
at the first sigh of phototoxicity )
 Liver toxicity : Trovafloxacin
Folate antagonists
B. Inhibitors of
Folate Synthesis
C. Inhibitors of
Folate Reduction
Mafenide
Pyrimethamine
Trimethoprim (TMP)
Silver sulfadiazine
Succinylsulfathiazole
Sulfacetamide
Sulfadiazine
Sulfamethoxazole (SMX)
Sulfasalazine
Sulfisoxazole
Folic Acid Antagonists : mechanism
 Coenzyme containing folic acid are required for the
synthesis of purines and pyrimidines (precursors of RNA
and DNA) and other compounds necessary for cellular
growth and replication.
 Human cannot synthesize folic acid, must obtain
preformed folate as a vitamin from the diet.
 Bacteria are impermeable to folic acid, must rely on
ability to synthesize folate de novo.
 Sulfonamides are inhibit the synthesis of folic acid.
 Second type folic acid antagonists (Trimethoprim) –
prevent the conversion of folic acid to its active,
coenzyme form (tetrahydrofolic acid)
Folic Acid Antagonists : adverse effect
 Pyrimethamine: hemolytic anemia,
agranulocytosis and eosinophilic alveolitis.
in high doses, pyrimethamine may inhibit
mammalian dihydrofolate reductase and cause a
megaloblastic anemia.
 Trimethoprim (TMP) : megaloblastic anemia
(because inhibitor dihydrofolate reductase,
inhibitor folic acid synthesis), leukopenia
Sulfonamides : adverse effect
 Crystalluria : Nephrotoxicity develops as a result
of crystalluria.
 Hypersensitivity : rash, angioedema, StevensJohnson syndrome, are fairly common.
 Hemolytic anemia : is encountered in patient
with glucose 6-phosphate dehydrogenase
deficiency.
 Kernicterus : This disorder may occur in
newborns because sulfa drug displace bilirubin
from binding sites on serum albumin.
D. Combination of Inhibitors
of Folate and Reduction
E. Urinary tract
Antiseptics
Co-trimoxazole
(TMP/SMX)
Methenamine
Nitrofurantoin
Urinary tract Antiseptics : mechanism
 1. Methenamine : In order to act, methenamine
must decompose at an acidic pH of 5.5 or less in
the urine, thus producing formaldehyde, which is
toxic to most bacteria.
 2. Nitrofurantoin (bacteriostatic) : Not known
(Sensitive bacteria reduce the drug to an active
agent that inhibits various enzymes and
damages DNA.)
 These drug do not achieve antibacterial levels in the
circulation, but because they are concentrated in the
urine, microoganisms at that site can be effectively
eradicated.
Urinary tract Antiseptics : adverse effect
1. Methenamine : major side effect is
gastrointestinal distress (high dose),
albuminuria, hematuria, and rash.
2. Nitrofurantoin : gastrointestinal
disturbances (most common), acute
pneumonitis and neurologic problem.
Others
Doxycycline
Ampicillin
Third generation – Cephalosporins
Aminoglycosides
Azithromycin
Fluconazole
Ceftriaxone