Antibiotics

Subodh Dhakal

Defintion

Antibiotics are the drugs that are used to kill or inhibit the growth of microorganisms.

Penicillin is a β lactam antibiotic which consisting penam moiety.

Penicillin was first discovered by Alexander Fleming (1928-1929). It was originally extracted from the fungus Penicillium notatum.

Penicillins consist of penam ring which is formed by the fusion of β lactam with thiazolidine.

In presence of alkali , Penicillin hydrolysis to give penicilloic acid by opening β lactam ring.

In presence of strong acid, penicillin undergoes opening of both β lactam and thiazolidine.

Classification of Penicillin

Penicillinase susceptible penicillin (Natural penicilin)

Penicillin G (Benzyl penicilin), Penicillin V (Phenoxy methyl penicillin)

Penicillinase resistant penicillin

Oxacillin, Cloxacillin

Amino penicillin

Amoxycillin, Ampicillin

Carboxy penicillin

Carbenicillin, Ticarcillin

Ureidopenicillin

Mezlocillin, Piperacillin

General chemistry of penicillins

Penicillins consist of penam ring which is the fusion of β lactam and thiazolidine ring.

C3, C5 and C6 of the penam ring are chiral.

Penicillins are the derivatives of 6-amino penicillanic acid.

All natural penicillins are dextro rotatory.

Penicillins get decomposed with moisture or penicillinase or strong acid/base.

Amoxicillin

Chemistry

Consists of penam ring.

Dimethyl group at position 2.

Carboxylic acid group at position 3.

Position 7 contains keto group.

Acetamido group substituted by amino and hydroxyphenyl group present at position 6 as side chain.

Physical Properties

It is available as white crystalline powder.

It is practically odorless.

It is slightly soluble in water and methanol.

Official salt form (Amoxycillin trihydrate) is slightly soluble in water and ethanol.

Its melting point is 194 °C.

Its Specific optical rotation is +248 deg to +268 deg

It is affected by moisture.

Stability and Storage

The stability is greatly affected by moisture. Thus it should be stored in a tightly closed container in a cool and dry place protected from moisture.

Uses

Ear infection, Nose infection, Throat infection, Sinus infection

Genitourinary Tract Infections

Skin and skin structure infection

LRTI

H pylori infection (in combination with other antibiotics)

Anthrax

Prophylaxis of infective endocarditits

Ampicillin

Chemistry

2-amino, 2-phenyl acetamido group is present at position 6.

Consists of penam ring.

Dimethyl group at position 2.

Carboxylic acid group at position 3.

Position 7 contains keto group.

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Physical Properties

Ampicillin occurs as white crystalline powder.

Ampicillin is slightly soluble in water and practically insoluble in ethanol.

Ampicillin trihydrate is sparingly soluble in water and ethanol.

It is sensitive to moisture.

It is unstable at high temperature.

Melting point: 208 degree celsius

Optical rotation = +287.9 deg at 20 °C

Storage

It is stored in a tightly closed container in a cool place at a temperature not exceeding 30°C.

Uses

Bacterial meningitis

Genitourinary infections

Gonorrhea

Respiratory tract infections

Gastrointestinal infections

Dental, Oral, Respiratory tract, and gastrointestinal tract procedures

Benzyl penicillin

Chemistry

2-phenyl acetamido group is present at position 6.

Consists of penam ring.

Dimethyl group at position 2.

Carboxylic acid group at position 3.

Position 7 contains keto group.

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Physical properties

It is official as sodium or potassium salt.

Both are white, crystalline powder having faint characteristic odor.

Both the salt are hygroscopic and very soluble in water.

They are susceptible to alkaline and acidic degradation.

Melting point: 82–83 ºC

Solubility in water : 210 mg/L

Stability and Storage

The stability of benzyl penicillin depends upon the moisture content. If the moisture content is less than 0.5 %, then at room temperature, benzyl penicillin is stable for 2-3 years.

Hence, it is stored in a tightly closed container protected from moisture.

Uses

Benzyl penicillin is used to treat a number of bacterial infections. This include

Pneumonia

Syphilis

Diptheria

Tetanus

Necrotizing enterocolitis etc

Clavulanic acid

Clavulanic acid is antibiotic isolated from Streptomyces clavuligerus. It acts as a suicide inhibitor of bacterial beta-lactamase enzymes.

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Clavulanic acid

Clavulanic acid is antibiotic isolated from Streptomyces clavuligerus. It acts as a suicide inhibitor of bacterial beta-lactamase enzymes.

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Chemistry

• Contains the fusion ring of beta lactam and oxazolidine.
• hydroxyethylidene moiety is present in position 2.
• Carboxylic acid at position 3

Physical properties

• It occurs as white to off white crystalline powder.
• Potassium clavulanate is freely soluble in water, soluble with methyl alcohol with decomposition.
• 1% solution in water has pH of 5.5 to 8.
• It is moisture sensitive.
• Melting point: 117.5-118 degree celsius

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Stability:

Since it is moisture sensitive it must be stored in airtight container.

Uses:

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Clavulanic acid is a medication that can be used in conjunction with amoxicillin to manage and treat bacterial infections like

otitis

• tonsillitis
• throat infections (pharyngitis)
• laryngitis
• bronchitis
• sinusitis and
• pneumonia.

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Cephalosporins

Cephalosporins are the bactericidal beta lactam antibiotics derived from the fungus Cephalosporium acremonium.

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It contains cephem ring which is the fusion ring of beta lactam and dihydrothiazine.

General chemistry

• Cephalosporins consists cephem ring which is the fusion of β lactam ring and dihydrothiazine.
• Most cephalosporins are the derivatives of 7-amino cephalosporanic acid.
• Carboxyl group is present at position C4.
• Different substituents attached at R and X

Classification

Common uses of Cephalosporins

Skin infections

Ear infections

Pneumonia

Meningitis

Kidney infections

Bone infections

Strep throat and other throat infections

Sexually transmitted diseases like Gonorrhea

Cephalexin *

Chemistry

derivative of cephem moiety which is the fusion of beta lactam and dihydrothiazine.

C3 contains methyl group.

Position 7 of cephem consist of 2-amino, 2-phenyl acetamido group.

Properties

It is a white or cream colored crystalline powder.

It has characteristic odor.

It is sparingly soluble in water, slightly soluble in alcohol.

Its 0.5% solution gives pH of 3.5 to 4.5

It is discolored on exposure to light.

With the mixture of sulphuric acid and nitric acid, it gives yellow color

Storage

Since, Cephalexin is light sensitive, it should be stored in a tight resistant container. Besides, it should be stored in a tightly closed container in a cool place.

Uses

Genitourinary infections

Uncomplicated cystitis

Bone infections

Otitis media

Skin infections

RTIs

Cefadroxil

Chemistry

derivative of cephem moiety which is the fusion of beta lactam and dihydrothiazine.

2-amino 2-(4-hydroxy phenyl) acetamido group is present at C7 of cephem ring.

Methyl group is present at C3 of the cephem ring.

Physical properties

It is available in monohydrate form.

It is white to off white colored crystalline powder.

It is slightly soluble in water and practically insoluble in ethanol.

It is moisture and light sensitive.

Stability and Storage

It loses its potency when exposed to moisture, sunlight or high temperature. So it should be stored in a tightly closed light resistant container in a cool and dry place.

Uses

Respiratory Tract Infection

Skin and soft tissue infections

Otitis media

Dental infections

Genitourinary infections

Cefaclor

Chemistry

derivative of cephem moiety which is the fusion of beta lactam and dihydrothiazine.

Chloro group is present at C3 of the cephem ring

2-amino, 2-phenyl acetamido group is present at C7.

Properties

It is white or slightly yellow crystalline powder.

It is odorless or tasteless.

It is slightly soluble in water and practically insoluble in methanol.

It is sensitive to light, moisture and high temperature.

Its melting point is 327ºC.

Storage

It is unstable above 30°C so it should be stored in a tightly closed, light resistant container in a cool and dry place.

Uses

Otitis media

Lower respiratory tract infections

Sinusitis

Skin and soft tissue infections

Bone and joint infections

Cefixime

Chemistry

derivative of cephem moiety which is the fusion of beta lactam and dihydrothiazine.

Carboxy methoxy imino and 2-aminothiazol-4-yl groups are present at the terminal carbon carbon of the acyl side chain.

Vinyl group is present at position 3.

Properties

It is white to almost white crystalline powder.

It is hygroscopic in nature,

It is slightly soluble in water, soluble in methanol.

It has bitter taste.

It is odorless in nature.

Melting point: 218-225ºC.

Stability and Storage

Since it is a hygroscopic powder, it should be stored in a tightly closed container in a cool and dry place.

Uses

Acute exacerbation of acute bronchitis

Otitis media

Pharyngitis/Tonsillitis

Uncomplicated Gonorrhea

Uncomplicated UTI

Typhoid fever (Off label)

Infection of other susceptible organisms like Haemophilus influenzae, Neisseria gonorrhoeae, Proteus mirabilis etc

Ceftriaxone

Chemistry

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derivative of cephem moiety which is the fusion of beta lactam and dihydrothiazine.

Methoxy imino and 2-aminothiazole (4-yl) groups are present at the terminal carbon carbon of the acyl side chain.

2- methyl, 5,6 dioxo 1,2,4 triazine (3-yl) sulfanyl methyl group at position 3.

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Properties

A white to yellowish-orange crystalline powder.

Ceftriaxone sodium is freely soluble in water; very slightly soluble in alcohol; sparingly soluble in methyl alcohol.

Solubility of Ceftriaxone is 0.105 g/l (very slightly soluble)

It is sensitive to moisture.

Melting point: 155 degree celsius.

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Stability and storage:

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Ceftriaxone is stored in airtight container.

Uses

Intra-abdominal Infections

Acute Bacterial Otitis Media

Pelvic Inflammatory Disease

Prosthetic Joint Infection

Meningitis

Acute Uncomplicated Pyelonephritis

Surgical Prophylaxis

Uncomplicated Gonococcal Infections