Drug for Urinary Tract Infections

Mustofa
Bagian Farmakologi & Toksikologi, FK, UGM
 remove liquid waste

Kidney keep balance of salts dan

others substances
produce hormone

Ureters carry urine from the kidneys

Urinary
tract
Bladder store urine

Urethra carry the urine to leave body

 An infection anywhere in the urinary tract
it occurs when bacteria enter the UT
Definition
UTIs can be painful and also become a
serious health problem

A strong, persistent urge to urinate

A burning sensation when urinating
Symptoms
Passing frequent, small amounts of urine
Urinary
Blood in the urine, strong-smelling urine
tract
infections Escherichia coli (E. coli)
(UTIs) Chlamydia
Cause Mycoplasma
Herpes simplex virus
Gonorrhea

Pyelonephritis : infection of the kidneys

Type Cystitis : infection of the bledder
Urethritis : infection of the urethra
 Test an urine sample
Diagnosis A urine culture

Women have more UTIs than men

One of five women will develop a UTI
Urinary Sexual intercourse seems to trigger
tract Risk
Menopause women are at a higher risk
infections factors
Any abnormality of UT that block urine flow
(UTIs) People with diabetes
Other disorder that suppresses immune system

Rarely lead to complications

Complication Acute or chronic pyelonephritis
Permanently damage the kidneys
Low birth weight or premature infants
 Drug for Urinary Tract Infections

Identification of organism

Antimicrobial susceptibility of
organism
Factors to consider
when selecting
antibiotic for
therapy in UTIs Host Status
Allergy history
Age
Pharmacokinetic factors
Renal function
Hepatic function
Pregnancy status
Genetic & metabolic abnormalities
Anatomical site of infection
Host defense
Susceptibility of Infecting Microorganisms

Disk diffusion method Dilution method

susceptible
intermediate MIC
resistence MBC
 Sulfanilamide
Sulfonamides Sulfadiazine
Sulfamethoxxazole

Trimethoprim
Benzylpyrimidine
Pyrimethamine

Drug for UTIs

Ampicilin
-lactame
Amoxicilin

Furan Nitrofurantoin
Sulfonamides
H

H
N SO2 NH2 Sulfanilamide

H3C CH3
H
N SO2 NH N Sulfisoxazole
H O

H
N SO2 NH
H Sulfadiazine
N CH3
O

N
H

H
N SO2 NH
Sulfamethoxxazole
N
Antimicrobial Activity of Sulfonamides

Active to both gram-positive and gram negative

bacteria, Nocordia, Chlamydia trachomatis some
protozoa.
Some bacteria are inhibited but not Pseudomonas,
Serratia, Proteus.
Many strains of meningococci, pneumococci,
streptococci, staphylococci and gonococci are now
resistant.
Drug of choice in UTIs, nocardiosis and other
bacterial infections.
Mechanism of action of Sulfonamides & Trimethoprim

H O H
N C N SO2 NH2
H OH
H

P-aminobenzoid acid Sulfonamides

Folic acid
H O
N C
H2C NH
H
HOOC CH

H N N CH2

HOOC CH2
Dihydro folic acid N OH

(DHF) H2N
N

OCH3
H3CO OCH3

DHFReductase
CH2

N NH2

Tetrahydro-folic acid H2N

N
H
N

Trimethorprim
H2C
H

H N N

Human cell N OH

N
H2N

Synthesis purine &

DNA Bacterium
Clinical Used of Sulfonamides

1. First infections of the urinary tract

Dose : sulfisoxazole, 2-4 g initially and 0.5
1 g/4-6 hr (150 mg/kg/d for children in
divided doses)
2. Chlamydial infections
Chlamydia trachomatis infections of the
genital tract, eye or respiratory tract
Tetracyclines and erythromycins are drug of
choice
3. Bacterial infections
Nocordia, beta hemolytic streptococci,
meningococci
Dose : 6-8 g/d
Adverse Reactions
1. Allergic reaction
Occur in 5% of patients
2. Commonest side effect
Fever, skin rashes, photosensitivity, urticaria,
nausea, vomiting or diarrhea
3. Urinary tract disturbance
Crystalluria, hematuria, nephrosis or alergic
nephritis.
4. Hematopoietic disturbances
Anemia, granulocytopenia, thrombocytopenia,
leukemoid reaction.
5. Others
Stomasitis, conjuctivitis, arthritis
Benzylpyrimidine

OCH3
H3CO OCH3

NH 2
N
CH2
H2N Cl

N
N NH2
C2H5
N
H2N

Trimethoprin Pyrimethamine
 Benzylpyrimidine
OCH3
H3CO OCH3

Stucture CH2

N NH2

Antimicrobial activity H N N
2

Inhibit DHFR bacteria 10.000 x than mamal cells

Have more active in prostatic and vaginal fluids

Absorption, distribution and excretion

Absorbed well from gut & distributed widely in
Trimethoprin body fluids and tissues
65-70% drug is proteinbound
50-60% are excreted in urine within 24 hr

Clinical uses
used alone in acute UTIs
dose : 100 mg every 12 hours

Adverse effect
anemia, leukopenia, granulocytopenia
 NH 2
N

Stucture H2N Cl

N
C2H5
Antimicrobial activity
Inhibit DHFR of protozoa more than mamal cells

Absorption, distribution and excretion

Absorbed well from gut & distributed widely in
Trimethoprin body fluids and tissues

Clinical uses
leishmaniasis, toxoplasmosis in combination with
sulfonilamides

Adverse effect
anemia, leukopenia, granulocytopenia
Trimethoprim-sulfamethoxazole combination (TMP-SMX)

Name
Bactrim, Septra, Cotrim, Kotrimaksazole

(TMP-SMX) Ratio of combination

dispensed in a 1 : 5 ratio
80 mg TMP : 400 mg SMX or 160 : 800 mg

Clinical uses
in recurrent infections of the lower or upper
urinary tract
Pneumocytis carinii pneumonia
Symptomatic Shigella enteritis
Systemic Salmonella infections
-lactamase (ampicillin and amoxicillin)

O
S CH3
R1 C HN
CH3
N
COOH
O

R= CH2 Penicillin G

CH Ampicillin
NH2

HO CH Amoxycillin
NH2
Antimicrobial activity of ampicillin and amoxicillin
have greater activity than penicillin G against
gram-negative bacteria
active to Salmonella infections e.g. typhoid

Clinical uses of ampicillin and amoxicillin

500 mg orally every 6-8, is used to treat common
UTI with gram negative bacteria or mixed secondary
bacteria infections of the respiratory tract
acute uncomplicated gonorrhea with penicillin G or
probenecid
bacterial meningitis in children (H. influenzae)

Adverse reactions
Allergic reactions
Gastrointestinal disturbance (nausea, vomiting,
diarrhea)
Nitrofurantoin
O
O
NH
O2N CH=N N

Antimicrobial activity
bacteriostatic & bactericidal for many gram-negative
and gram-positive bacteria
the mechanism of actios is not known.

Absorption, metabolism and excretion

nitrofurantoin is rapidly and completely absorbed
from gastrointestinal tract
nitrofurantoin is also metabolized and excreted
rapidly
the concentration in lymph and renal is high.