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Anti-infective Agents 317
Nomenclature: N-[(4-Aminophenyl) sulfonyl]acetamide; acetyl-(4-aminophenyl)
sulfonylazanide.
Properties: It occurs as the monohydrate; white, odorless, crystalline powder with slightly bitter
taste. It is slightly soluble in 96% ethanol, sparingly soluble in acetone, and practically insoluble
in ether and chloroform.
Uses:
➢ Sulfacetamide is used in the treatment of pityriasis versicolo and rosacea.
➢ It also has anti-inflammatory properties when used to treat blepharitis or conjunctivitis (in
eye-drop solution).
➢ It is also used for the treatment for mild forms of hidradenitis suppurativa.
➢ Sulfacetamide has antibacterial activity and is used to control acne.
➢ There are several prescription of topical products containing sulfacetamide, such as
foams, shampoos, cream and washes.
Dosage Forms:
➢ Sulfacetamide sodium ointment USP, 10%, is a sterile, topical anti-bacterial agent for
ophthalmic use. Sulfacetamide Sodium USP, 100 mg in an ointment base of white
petrolatum and mineral oil.
➢ Sulfacetamide Sodium Ophthalmic Ointment USP, 10%, is supplied in 3.5 gram (1/8 oz)
sterile, tamper evident tubes.
➢ Sulphacetamide Eye Drop, 1 vial of 10 ml
Stability: Sulfacetamide is stable under normal temperatures and pressures. No dangerous
reactions occur under known conditions of normal use.
11.6.6 Mafenide Acetate
Brand Name: Sulfamylon (Sterling Winthrop)
Mafenide acetate (para-aminomethylbenzene sulfonamide) chemically designated as
α-amino-p-toluene sulfonamide monoacetate. It is a synthetic antimicrobial agent. It has the
following structural formula:
Nomenclature: 4-(amino methyl)-benzene sulphonamide
Properties: It occurs as white color, crystalline solid, soluble in DMSO 1 mg/mL, inert
atmosphere 2°C to 8°C.
318 Text Book of Pharmaceutical Chemistry
Uses:
➢ Mafenide acetate is a topical antibiotic used to treat wound infections.
➢ It is used topically as an adjunctive therapy for second- and third-degree burns.
➢ It works by destroying microorganisms that could cause an infection in an open wound.
Killing of bacteria cause wound healing and reduces the possibility of the bacteria
spreading to neighboring skin or blood, reducing the danger of a major blood infection
(sepsis).
➢ It is bacteriostatic against various gram-positive and gram-negative bacteria; comprises
Pseudomonas aeruginosa. Mafenide acetate is specifically effective against Clostridium
welchii in topical application and was used during World War II.
➢ Mafenide is more appropriate for non-facial burns, while chloramphenicol/prednisolone
or bacitracins are more appropriate for facial burns.
Dosage Forms: Mafenide acetate for 5% topical solution mafenide acetate is not effective orally.
Cream should be applied to the burned area at all times.
Storage: Store solution at 20°C to 25°C with excursions permitted to 15°C to 30°C at controlled
room temperature.
11.6.7 Cotrimoxazole
Brand Name: Bactrim, Bactrim DS, Bactrim IV, Septra IV, SMZ-TMP DS, Sulfatrim Pediatric
Cotrimoxazole is a combination of trimethoprim and sulfamethoxazole. It is a
synthetic antibacterial combination product. It is available in DS (double strength) tablets, each
containing 800 mg sulfamethoxazole and 160 mg trimethoprim; in tablets, each containing 400
mg sulfamethoxazole and 80 mg trimethoprim for oral administration.
Fig. 2: Cotrimoxazole
Sulfamethoxazole is N1-(5-methyl-3-isoxazolyl) sulphanilamide; Trimethoprim is 2,4-
diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine
Properties: Sulfamethoxazole occurs as a white to light yellow, odorless, tasteless bitter
compound. It is very slightly soluble in water, but is soluble in 1 in 50 of alcohol and 1 in 3 of
acetone. It is also soluble in alkali hydroxides. A 10% suspension in water has a pH of 4 to 6.
Anti-infective Agents 319
Uses: Cotrimoxazole is used to treat ear infections, urinary tract infections, bronchitis, traveler’s
diarrhea and shigellosis. It is also used to prevent and treat a certain type of pneumonia
(pneumocystis-type) and middle ear infections (otitis media). It is also used to prevent or treat
pneumocystis jiroveci pneumonia or pneumocystis carinii pneumonia (PCP), a very serious kind
of pneumonia.
Storage and Stability: Store Sulfamethoxazole/Trimethoprim tablets at room temperature, 68°F
to 77°F (20°C to 25°C). Store Sulfamethoxazole/Trimethoprim injection solution at room
temperature (20°C to 25°C). Protect from light. Sulfamethoxazole solution can be sterilized by
autoclaving. Do not refrigerate the injection solution.
Dosage Forms:
➢ Intravenous solution (80 mg-16 mg/mL)
➢ Oral suspension (200 mg-40 mg/5 ml)
➢ Oral tablet (400 mg-80 mg; 800 mg-160 mg)
The normal adult dose of co-trimoxazole to treat a UTI (urinary tract infection) is trimethoprim-
sulfamethoxazole 160 mg-800 mg (1 double-strength tablet) orally every 12 hours for 10 to 14
days.
11.6.8 Dapsone
Brand Name: Dapsone
Dapsone (DDS) is a primary treatment for dermatitis herpetiformis. It is an antibacterial drug
for susceptible cases of leprosy.
Nomenclature: DDS, (4, 4′-diaminophenyl sulfone)
Properties: It is a white, odorless crystalline powder that is slightly soluble in water and
sparingly soluble in alcohol. This compound in the pure form is light stable, but traces of
impurities, including water, make it photosensitive and thus susceptible to discoloration in light.
Uses:
➢ Dapsone belongs to a class of drugs called antileprosy agents. It is used to treat the
symptoms of dermatitis herpetiformis, leprosy, tuberculoid or lepromatous disease.
➢ It is also used with other drugs to treat Hansen’s disease.
➢ It is widely used for all types of leprosy, often in combination with Clofazimine and
Rifampin.
➢ Dapsone is also used for the treatment of dermatitis herpetiformis and is sometimes used
with pyrimethamine for treatment of malaria and with trimethoprim for PCP.
320 Text Book of Pharmaceutical Chemistry
Dosage Forms: 25 mg, 100 mg
➢ Dermatitis Herpetiformis: 50 mg to 300 mg
➢ Leprosy: 100 mg per day in combination with other antibiotics
➢ Tuberculoid diseases: 100 mg per day
➢ Pneumocystis: 100 mg per day in the initial stage the treatment includes Rifampin with
Dapsone, followed by Dapsone alone.
Storage: Dapsone tablets should be stored at 20°C to 25°C and protected from light. Store the
medicine in a closed container at room temperature, away from heat, moisture, and direct light.
Keep from freezing. Do not keep outdated medicine or medicine no longer needed.
11.7 EXERCISE
A. Long Answer Type Questions
1. What are antifungal agents? Classify them and give the structure and uses of
amphotericin-B.
2. Write a detail account on types of fungal infections.
3. What are antimalarial agents? Write the chemical structure, uses and important chemical
properties of Quinine Sulphate.
4. Write the classification of antimalarial agents on the basis of chemical structure.
5. Give the uses, chemical and physical properties of Mefloquine.
6. Write the dosage form and uses of Pyrimethamine.
7. Classify antimalarial agents on the basis of mechanism of action.
8. Explain in brief about sulphonamides. Write the chemical structure, uses and important
chemical properties of any three sulphonamide drugs.
9. Write short notes on:
(a) Cotrimoxazole
(b) Dapsone
10. Give the uses, chemical and physical properties of Sulfacetamide.
11. Classify Sulfonamide on the basis of duration of action.
B. Short Answer Type Questions
1. What are polene antibiotics?
2. Define fungal infections.
3. Give properties of Griseofulvin.
4. Give the uses of Amphotericin B.
Anti-infective Agents 321
5. Define antimalarial agents.
6. Explain in brief about the chemistry and structure of Mefloquine.
7. Write the structure of Quinine Sulphate.
8. Give uses of Cycloguanil.
9. Write the structure and uses of Primaquine Phosphate.
10. Write the chemical name of Pyrimethamine.
11. Write the brand name of Artemisinin.
12. Define sulfonamide.
13. Differentiate between short and long acting sulfonamides.
14. Write the structure of Sulfacetamide.
15. Give uses of Mafenide acetate.
16. Write the structure of Dapsone.
17. Write the chemical name of Sulfamethoxazole.
18. Define Sulfanilamide.
C. Fill in the Blanks
1. Amphotericin B belongs to the ___________ antibiotics.
2. Griseofulvin is used to treat ___________.
3. UTIs stand for ___________.
4. Basic nucleus of Miconazole is ___________.
5. Norfloxacin is mainly used in the treatment of ___________.
6. Ethambutol is a derivative of ___________.
7. Pretomanid is a nitroimidazole-based antibiotic used for the treatment of ___________.
8. Amantadine is an amino derivative and is a member of the class ___________.
9. Acyclovir is a synthetic analogue of the ___________ nucleoside.
10. Zidovudine is a synthetic dideoxynucleoside used to treat and prevent ___________.
11. Remdesivir is an RNA polymerase inhibitor with potent ___________ activity.
12. Primaquine is a ___________ derivative with antimalarial activity.
13. Mefloquine is used in the prophylaxis and treatment of malaria caused by ___________
and ___________.
14. Clotrimazole is the mixture of ___________ and ___________
15. Sulfamethoxazole is used for the treatment of ___________.
16. Sulphathiazole is used for the treatment of ___________.
322 Text Book of Pharmaceutical Chemistry
Answers:
1. Polyenes
2. Fungal infections
3. Urinary tract infections
4. Imidazole
5. Urinary Tract Infection
6. ethylenediamine
7. multi-drug-resistant pulmonary tuberculosis
8. Adamantanes
9. Purine
10. HIV/AIDS
11. Antiviral activity.
12. 8-aminoquinoline
13. Plasmodium falciparum and Plasmodium vivax
14. Sulfamethoxazole and Trimethoprim
15. Urinary tract infections
16. Vaginal infections
Chapter
12
ANTIBIOTICS
STRUCTURE
12.1 Introduction
12.2 Tetracyclines
12.3 Macrolid Antibiotics
12.4 Miscellaneous
12.5 Exercise
OBJECTIVES
Antibiotics: Penicillin G, Amoxicillin, Cloxacillin, Streptomycin, Tetracyclines: Doxycycline,
Minocycline,
Macrolides: Erythromycin, Azithromycin, Miscellaneous: Chloramphenicol, Clindamycin
12.1 INTRODUCTION
The term antibiotics are derived from the Greek word antibiosis, which means “against life”
(anti-against, bios-life). Antibiotics are chemical substances obtained from various species of
microorganisms (bacteria, fungi, actinomycetes) that suppress the growth of other
microorganisms and eventually may destroy them. Antibiotics are substances that inhibit the
growth and multiplication of bacteria or kill them completely. These are the antimicrobials that
are used to treat bacterial infections in (or on) the human body.
The major points of difference between the antibiotics are physical, chemical,
pharmacological properties, antibacterial spectra, and mechanism of action. They have made it
possible to cure diseases caused by bacteria, such as pneumonia, tuberculosis, and meningitis, and
they save the lives of millions of people around the world.
The antimicrobial spectrum of an antibiotic consists of a range of microorganisms it can kill
or inhibit. Based on their spectrum of activity, antibiotics are classified as broad-spectrum
antibiotics, extended-spectrum antibiotics, or narrow-spectrum antibiotics.
324 Text Book of Pharmaceutical Chemistry
➢ Broad-spectrum antibiotics: Antibiotic that is effective against a wide range of bacteria
or that acts on the two major bacterial groups, gram-positie and gram-negative are called
broad-spectrum antibiotics.
➢ Narrow-spectrum antibiotics: Antibiotics that kill just gram-positive or gram-negative
bacteria or could be specific to one type of bacteria. These are only effective against a
narrow range of bacteria. For example, Penicillin G is very effective at killing gram-
positive bacteria, but not very effective against gram-negative bacteria.
Classification of Antibiotics Based on Chemical Structure
1. β-lactam antibiotics: Penicillin, Cephalosporin, Monobactams, etc.
2. Tetracycline antibiotics: Oxytetracycline, Doxycycline, etc.
3. Aminoglycoside antibiotics: Stretomycin, Gentamycin, Neomycin, etc.
4. Macrolide antibiotics: Erythromycin, Clarithromycin, Azithromycin, etc.
5. Polypeptide antibiotics: Polymyxin B
6. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin, etc.
7. Nitrobenzene derivatives: Chloramphenicol
8. Other antibiotics: Clindamycin, Novobiocin, etc.
Penicillins are a group of antibiotics obtained from Penicillium moulds, principally
P. chrysogenum. Penicillin may be divided into two classes: the naturally occurring penicillins
(obtained naturally by mould) and the semi-synthetic penicillins (those in which the structure of a
chemical substance—6-aminopenicillanic acid) found in all penicillins.
Classification of Penicillin
➢ Natural Penicillins: Penicillin G, Penicillin V.
➢ Semi-synthetic Penicillinase/Resistant Penicillins: Methicillin, Nafcillin, Isoxazolyl
Penicillins (Cloxacillin/Dicloxacillin/Oxacillin/Flucloxacillin).
➢ Amino Penicillins: Ampicillin, Amoxicillin.
➢ Carboxy penicillins: Carbencillin, Carbencillin phenyl, Carbencillin indanyl, Ticarcillin.
➢ Ureidopenicillins: Piperacillin, Mezlocillin, Azlocillin.
Antibiotics 325
12.1.1 Penicillin G (Benzyl Penicillin)
Penicillin G or benzyl penicillin is a naturally occurring beta-lactam antibiotic. It is produced
by fermentation of Penicillium chrysogenum. The structure of benzyl penicillin contains a
6-aminopenicillanic acid as a penicillin nucleus that further consists of a β-lactam ring and
thiazolidine ring and benzyl side chain moiety. Penicillin G is metabolized to penicilloic acid
which is microbiologically inactive.
IUPAC Name: (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo
[3.2.0]heptane-2-carboxylic acid
Properties: It occurs as white or colorless, odorless crystalline, amorphous powder. It is
practically insoluble in water; soluble in peanut oil; freely soluble in methanol, benzene,
chloroform, and amyl acetate; sparingly soluble in water; insoluble in petroleum ether; soluble
in methanol, ethanol, ether, ethyl acetate, benzene, chloroform and acetone.
Mechanism of Action: Penicillin G acts by binding to specific penicillin-binding proteins (PBPs)
located inside the bacterial cell wall, inhibits the bacterial cell wall synthesis, cell lysis causes by
bacterial cell wall autolytic enzymes such as autolysins.
Uses:
➢ Penicillin is used for the treatment of bacterial infections, for treating pneumonia, strep
throat, staph infection, diphtheria, meningitis, gonorrhea (sexually-transmitted disease
(STD), and syphilis.
➢ It is used in neuro syphilis, congenital syphilis (presence of clinical signs in the neonate
and lack of adequate treatment in the mother), brain abscesses and pasteurellosis.
➢ It is used in gingivostomatitis, pulmonary infections, and genital disease produced by
synergistic action of fusobacterium nucleatum.
➢ It is used to prevent heart valve infection before dental procedures for people with certain
cardiac conditions.
➢ Penicillin G is effective against infections caused by some forms of Streptococcus
pyogenes, Streptococcus pneumoniae, Staphylcoccus, Clostridium bacteria, and many
others.
Dosage Forms:
➢ Diphtheria: Child: 50000 IU (30 mg)/kg every 6 hours (maximum 4 MIU or 2.4 g daily).
Adult: 1 MIU (600 mg) every 6 hours.
326 Text Book of Pharmaceutical Chemistry
➢ Neuro syphilis: Adult: 2 to 4 MIU (1.2 to 2.4 g) by IV injection every 4 hours.
➢ Congenital syphilis: 50000 IU (30 mg)/kg by IV injection every 12 hours from D1 to
D7, then 50000 IU (30 mg)/kg by IV injection every 8 hours from D8 to D10.
Storage: Penicillin G potassium or penicillin G sodium powders for injection may be stored at
room temp less than 15°C. It is moderately hygroscopic and dry powders of the drugs should be
protected from moisture to prevent hydrolysis.
Officials:
➢ Benzylpenicillin Potassium, I.P.
➢ Benzylpenicillin Injection, I.P.
➢ Benzylpenicillin Sodium, I.P.
12.1.2 Amoxicillin
Brand Names: Amoxil, Augmentin, Clavulin, Moxatag, Omeclamox, Prevpac, Talicia
Amoxicillin is anhydrous form of a broad-spectrum, semi-synthetic aminopenicillin antibiotic
with bactericidal activity. It is an amino-penicillin, in which the substituent at position 6 of
the penam ring is a 2-amino-2-(4-hydroxyphenyl) acetamido group.
IUPAC Name: 6β-[(2R)-2-amino-2-(4-hydroxyphenyl) acetamido]-2,2-dimethylpenam-3α-
carboxylic acid
Properties: It occurs as off-white crystalline powder/crystalline solid with melting point 194°C.
It is soluble in water.
Uses:
➢ Amoxicillin is used for the treatment of different types of bacterial infections such
as tonsillitis, bronchitis and pneumonia.
➢ It is used in infections of the ear, nose, throat, skin, or urinary tract.
➢ Used in genitourinary tract, skin, skin structure, and lower respiratory tract infection.
➢ Amoxicillin in combination with calvulanic acid used to treat acute bacterial sinusitis,
community acquired pneumonia, lower respiratory tract infections, acute bacterial otitis
media and urinary tract infections.
Storage: It should be stored in a tightly closed container in a dry and well-ventilated place at
temperature 2°C to 8°C. Amoxicillin capsules – 125 mg and 250 mg, chewable tablets, and
powder for oral suspension should be stored in tight containers at 20°C or lower.