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185
Antibiotics
was effective in the treatment of hemolytic streptococcal infections in the mice. For this work, he
was awarded Nobel Prize in medicine in 1938.
N
N
SO
2
NH
2
NH
2
H
2
N
This discovery led to the synthesis of at least 5500 congeneric substances which are known
as sulfonamides. The term sulfonamide is usually employed as a generic name for the derivatives
of para amino benzene sulfonamides. Sulfanilamide is the basic skeleton of this category.
NH
2
S
O
O
H
2
N
History
Sulfonamide drugs were the first antibiotics to be used systematically and paved the way for
the revolution in medicine. The first sulfonamide was Prontosil and was a prodrug. Experiments
with Prontosil began in 1932 in the laboratories of Bayer.
Prontosil, as Bayer named the new drug, was the first medicine ever discovered that could
effectively treat a range of bacterial infections.
In the body, it gets metabolized to a colorless active compound called Sulfanilamide.
Development in the Subject
The drug has very low water solubility and therefore gets crystallized in the kidney, due to
its first pKa of around 10. Therefore newer analogs having lower pKa of around 5-6 and higher
solubility were synthesized to prevent this complication.
Mechanism of Action
Sulfonamides compete with p-aminobenzoic acid (PABA) for the enzyme dihydropteroate
synthetase (DHPS) and inhibit it which is important in the formation of folic acid in the bacteria.
Sulfonamides are bacteriostatic.
Potential Adverse Effect
Kernicterus (Bilirubin induced brain dysfunction).
Stevens-Johnson syndrome (epidermal necrolysis of skin).
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Chemistry
Contraindication
Contraindicated in the children below the age of twelve.
They are classified as follows:
(a) Short Acting Sulfonamides
Sulfadiazine
(b) Intermediate Acting Sulfonamides
Sulfamethoxazole
(c) Long Acting Sulfonamides
Sulfadoxine
Sulfamethopyrazine
(d) Miscellaneous Sulfonamides
Sulfacetamide sodium
Sulfasalazine
Silver sulfadiazine
Mafenide
Sulfadiazine
Structure:
O
S
NH
N
N
NH
2
O
Chemical name: 4-Amino-N-pyrimidin-2-yl-benzenesulfonamide
Uses: It is commonly used to treat urinary tract infections, burns, infection in otitis media
and prevention of rheumatic fever.
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Antibiotics
Formulations: Capsule, Gel and Ointment.
Brand names: Lantrisul, Neotrizine, Sulfa-Triple#2, Sulfadiazine and Sulfaloid.
Sulfamethoxazole
Structure:
O
S
NH
NH
2
O
N
O
Chemical name: 4-Amino-N-(5-methylisoxazol-3-yl)-benzenesulfonamide
Uses: It is commonly used to treat urinary tract infections, bronchitis, and prostatitis.
Adverse effect: Potential adverse allergic condition urticaria/hives (skin rashes).
Formulations: Tablet and Capsule.
Brand name: Gantanol.
Sulfacetamide
Structure:
O
S NHH
2
N
O
H
3
C
O
Chemical name: N-[(4-Aminophenyl)sulfonyl]-acetamide
Uses: It is commonly used to treat urinary tract infections, burns, acne and dermatitis.
Formulations: Tablet, Lotion and Ointment.
Brand names: Klaron, Ovace (Plexion: when combined with 5% sulfur)
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Chemistry
Mafenide
Structure:
O
S NH
2
O
H
2
N
Chemical name: 4-(Aminoethyl)-benzenesulfonamide
Uses: It is commonly used to treat infections during second and third-degree burns.
Formulations: Cream, Ointment and Gel.
Brand name: Sulfamylon.
Co-trimoxazole
It is the best well-known combination of Sulfamethoxazole and Trimethoprim in the ratio of
(5:1). It provides a synergistic effect.
Mainly useful in the treatment of urinary tract infections, respiratory tract infections,
gastrointestinal tract infections, septicemia, cholera and to prevent pneumonia in HIV patients.
14.2 DRUGS USED IN URINARY TRACT INFECTION
Many drugs are used to treat urinary tract infections mainly because of their ability to
develop required concentration in the urinary bladder, adequate to inhibit the growth or kill the
infective organisms.
Urinary tract infections don’t always cause signs and symptoms, but when they do they may
include:
A strong, persistent urge to urinate.
A burning sensation when urinating.
Passing frequent, small amounts of urine.
Urine that appears cloudy.
Urine that appears red, bright pink, or cola-colored - a sign of blood in the urine.
Strong smelling urine.
Pelvic pain, in women – especially in the center of the pelvis and around the area of the
pubic bone.
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Antibiotics
Types of Urinary Tract Infections
1. Kidneys (Acute pyelonephritis): It causes upper back and side pain, high fever, nausea,
and vomiting.
2. Bladder (Cystitis): It causes pelvic pressure, lower abdomen discomfort, frequent
painful urination, and sometimes blood in the urine.
3. Urethra (Urethritis): It causes a burning sensation with urine discharge.
The most common UTIs occur mainly in women and affect the bladder and urethra. Infection
of the bladder (cystitis) is usually caused by E. coli, a type of bacteria commonly found in the
gastrointestinal (GI) tract. However, sometimes other bacteria are also responsible.
Classification of Anti-UTI Agents
(a) Non-Fluorinated quinolines
Nalidixic acid
(b) Fluoroquinolones
(i) First-generation
Norfloxacin
Cinoxacin
Ofloxacin
Pefloxacin
Ciprofloxacin
(ii) Second-generation
Moxifloxacin
Lomefloxacin
Sparfloxacin
Levofloxacin
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Chemistry
Nalidixic acid
Structure:
N N
O
HO
O
Chemical name: 1-Ethyl-7-methyl-4-oxo-[1,8]-naphthyridine-3-carboxylic acid.
Uses: Used in the treatment of UTI caused by gram-negative bacteria.
Formulations: Tablet and Suspension.
Brand names: Diarlop, Gramoneg, and Win-18.
Cinoxacin
Structure:
N
N
O
HO
O
O
O
Chemical name: 1-Ethyl-1,4-dihydro-4-oxo-[1,3]-dioxolo-[4,5-g]-cinnoline-3-carboxylic
acid.
Uses: Used in the treatment of UTI caused by gram-negative bacteria.
Formulation: Tablet.
Brand names: Mecicon and Cinobac.
191
Antibiotics
Ciprofloxacin
Structure:
O
N
F
N
NH
O
HO
Chemical name: 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic
acid.
Uses: It is useful in a wide variety of infections including infections of bones and
joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections,
cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid (Infection that causes open
sores on or around the genitals of men and women).
Formulations: Tablet and Eye drop.
Brand names: Ciplox and Quintor.
Ofloxacin
Structure:
NN
F
O
OH
O
N O
Chemical name: (RS)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-
1azatricycltrideca-5(13), 6, 8, 11-tetraene-11-carboxylic acid.
Uses: Useful in the treatment of
Acute bacterial exacerbations of chronic bronchitis
Community-acquired pneumonia.
Uncomplicated skin and skin structure infections.
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Chemistry
Nongonococcal urethritis and cervicitis.
Mixed Infections of the urethra and cervix.
Acutepelvic inflammatory disease.
Uncomplicated cystitis.
Formulations: Tablet, Eye drop, and Injectable.
Brand names: Oflox, Exocin, and Zanocin.
Norfloxacin
Structure:
NN
F
O
OH
O
HN
Chemical name: 1-Ethyl-6-fluoro-4-oxo-7piperazin-1-yl-1H-quinoline-3-carboxylic acid.
Uses: Useful in the treatment of
Acute bacterial exacerbations of chronic bronchitis
Uncomplicated urinary tract infections (including cystitis)
Complicated urinary tract infections (restricted use)
Uncomplicated urethral and cervical gonorrhea
Prostatitis due to Escherichia coli.
In Syphilis treatment
Formulations: Tablet, Eye drop and Suspension.
Brand names: Uroflox and Bacigyl.
193
Antibiotics
Sparfloxacin
Structure:
NN
F
O
OH
O
HN F
NH
2
Chemical name: 5-Amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimehtylpiperazin-1yl]-6,8-
difluoro-4-oxo-quinoline-3-carboxylic acid.
Uses: It is used for treating community-acquired lower respiratory tract infections (acute
sinusitis, exacerbations of chronic bronchitis caused by susceptible bacteria, community-acquired
pneumonia).
Formulations: Tablet and Eye drop.
Brand names: Sparquin, Spardac, and Zospar.
Lomefloxacin
Structure:
NN
F
O
OH
O
HN F
Chemical name: (RS)-1-Ethyl-6,8-difluoro-7-(3-mehtylpiperazin-1-yl]-4-oxoquinoline-3-
carboxylic acid.
Uses: It is useful in the treatment of community-acquired lower respiratory tract infections
(acute sinusitis, exacerbations of chronic bronchitis).
Formulations: Tablet and Eye drop.
Brand names: Lomibact and Lox-400.
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Chemistry
14.3 PENICILLINS
Penicillins are obtained from the fungus Penicillium notatum and Penicillium chrysogenum.
It is composed of the β-lactam ring and thiazolidine ring structures. It mainly inhibits the cell wall
synthesis of bacteria.
N
S
H
CH
3
CH
3
O
H
N
O
OH
R
O
(a) Natural Penicillin
Penicillin-G (Benzylpenicillin)
(b) Semi-synthetic Penicillin
(i) Acid-resistant penicillin
Penicillin-V (Phenoxymethylpenicillin)
(ii) Penicillinase (β-lactamase) resistant
Methicillin
Nafcillin
Oxacillin
Flucloxacillin
Cloxacillin
Dicloxacillin
(iii) Broad-spectrum penicillins (Aminopenicillins)
Ampicillin
Amoxicillin
Bacampicillin
Piperacillin
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