PHARMACOLOGY BY BRIAN MUTHABALI (0777105427 / 0702843892 / mb42203@gmail.

com)

THE MACROLIDE ANTIBIOTICS

The Macrolide antibiotics are named so because they contain many member Lactose rings
to which are attached one or more Deoxysugars. The macrolides are a group of antibiotics
with a macrocyclic lactone structure to which one or more deoxy sugars are attached.
Erythromycin was the first of these drugs to find clinical application, both as a drug of first
choice and as an alternative to penicillin in individuals who are allergic to beta-lactam
antibiotics. The newer members of this family, clarithromycin (a methylated form of
erythromycin) and azithromycin (having a larger lactone ring), have some features in
common with, and others that improve on, erythromycin. Telithro mycin, a semisynthetic
derivative of erythromycin, is the first“ketolide” antimicrobial agent that has been approved
and is now in clinical use. Ketolides and macrolides have very similar antimicrobial
coverage. However, the ketolides are active against many macrolide-resistant gram positive
bacteria.
Note;
1. The macrocyclic lactones (avermectins and milbemycins) are products or chemical
derivatives of soil microorganisms belonging to the genus Streptomyces.
2. Deoxy sugars are sugars that have had a hydroxyl group replaced with a hydrogen
atom.
Structure of Macrolides

Mode of Action
The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus
inhibiting the translocation steps of protein synthesis. They may also interfere at other
steps, such as transpeptidation. Generally considered to be bacteriostatic, they may be
bactericidal at higher doses. Their binding site is either identical or in close proximity to
that for clindamycin and chloramphenicol.
The Macrolide antibiotics are active against gram positive bacteria like Streptococcus
Pneumonae. They have a moderate action against gram negative bacteria.
Macrolides may either be bactericidal or bacteristatice depending on the type of bacteria
being treated. They are bactericidal in a small number of rapidly dividing micro-organisms.

Note: Erythromycin and other macrolide antibiotics can interfere with the action of
Chloramphenicol because it also acts on the 50s Ribosomal subunits.

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Illustration of different mechanisms of action of antibiotics

Pharmacokinetics
Well absorbed orally and distributed adequately to most sites except the brain, macrolides
are inactivated by hepatic N-demethylation, 15% being eliminated unchanged in the urine.
Food delays absorption but may reduce gastro-intestinal side effects.

DNA methylation is a process by which methyl groups are added to the DNA
molecule. Methylation can change the activity of a DNA segment without changing the
sequence.
For example

Examples of Macrolide antibiotics include;

I. Erythromycin
II. Clarithromycin
III. Clindamycin
IV. Spectinomycin
V. Azithromycin

ERYTHROMYCIN

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This drug is effective against many of the same organisms as penicillin G; therefore, it may
be used in patients who are allergic to the penicillins.
Resistance to erythromycin is becoming a serious clinical problem. For example, most
strains of staphylococci in hospital isolates are resistant to this drug.

Pharmacokinetics of Erythromycin

1. It is absorbed from the upper part of the small intestines. It is partially destroyed
by gastric acid and it’s always prepared/ formulated with an enteric coat for this
reason.
2. It is widely distributed in body tissues except in the CNS because of its big
molcecular weight.
3. It’s concentrated and metabolized in the liver by Demethylation.
4. The non-ionized form of this drug enables it to penetrate the tissues; it is one of
the few antibiotics that penetrate the prostatic fluids.

Indications
1. It is a drug of choice for the treatment of Mycoplasma pneumonia
2. For treatment of legionella infections
3. Gastroenteritis caused by Campylobacter jujeni
4. It is the first choice drug in the treatment of Diptheria, Pertusis (whooping
cough) and Chlamydial infections.
5. Very useful alternative for penicillin allergic patients infected with
Staph.pyogens, staph.pneumoniae, and Treponema pallidum (Notorious for
causing Syphilis)
6. Used for the treatment of Gonorrhea and Gonococcal Urethritis.
7. Treatment of Acne
8. Sinusitis
9. Bronchitis
10. Urinary tract infections mostly during all trimesters of pregnancy

Dose and preparations

1. Enteric coated tablets of 250mg or as a film coated tablet containing 500mg.

2. Erythromycin estolate in capsules of 500mg and 250mg
3. Oral suspension of 125mg and 250mg/5ml
4. i.v infusion powder for reconstitution in 1g vial. The injection powders are
prepared either as Erythromycin Gluceptate or Erythromycin Lactobionate. 250mg
and 500mg vials are also available.

Dose; Adult 25omg -500mg 6 hourly

Child 50mg/kg/day divided into 4 portions 6 hourly.

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Food should not be given immediately or before oral administration of Erythromycin, the
drug is poorly absorbed with food.

By i.v infusion for adults and children give 50mg/ Kg daily by continuous infusion or by
divided doses given 6 hourly but it should be used in very severe infections.
The i.m administration of Erythromycin is not recommended because it’s very painful.

CLARITHROMYCIN
This antibiotic has a spectrum of antibacterial activity similar to that of erythromycin. It
has lesser side effects.
Indications
1. Helicobacter pyroli infection (gastritis and Peptic ulcer disease)
2. Skin and soft tissue infections
3. Respiratory tract infections
4. Otitis media
5. Mycobacterium avium complex infections

Preparations
1. Tablets of 250mg and 500mg
2. Pediatric suspension for reconstitution with water to 125mg/5ml and 250mg/5ml
3. Powder for reconstitution given i.v in 500mg vials

Dose
Orally 250mg-500mg 12 hourly for 7/7
<8kg= 7.5mg/Kg 12 hourly
8-11Kg (1-2years) 62.5mg BID
12-19Kg (3-6years) 125mg BID
20-29Kg (7-9 years) 187.5mg BID
30-40Kg (10-12 years) 250mg BID
By i.v infusion 500mg BID
Parenteral route not recommend in children.

AZITHROMYCIN
Although less active against streptococci and staphylococci than erythromycin,
Azithromycin is far more active against respiratory infections due to H. influenzae and
Moraxella catarrhalis. Azithromycin is now the preferred therapy for urethritis caused by
Chlamydia trachomatis. It also has activity against Mycobacterium avium-intracellulare
complex in patients with acquired immunodeficiency syndrome and disseminated
infections.

Preparations
I. Capsules of 250mg

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II. Oral suspension of 200mg/5ml after reconstitution

III. Ophthalmic drops

Dose: Adults 500mg O.D

Children; 10mg/Kg
Indications
I. RTIs (Respiratory Tract Infections)
II. Otitis media
III. Non-gonococcal urethritis
IV. Typhoid due to multiple drug resistance
V. Urinary Tract Infections
VI. Skin Infections

Comparing Erythromycin, Azithromycin and Clarithromycin

Each of these has greater activity than erythromycin against H. influenzae. Azithromycin is
less effective against Gram positive bacteria than erythromycin, but has a wider spectrum
of activity against Gram-negative organisms. Clarithromycin is an erythromycin derivative
with slightly greater activity than the parent compound; tissue concentrations are higher
than with erythromycin. It is given twice daily. Azithromycin and clarithromycin are more
expensive than erythromycin, but cause fewer gastro-intestinal side effects.

General side effects of Macrolide antibiotics

1. GIT irritation characterized by Nausea, Vomiting, abdominal discomfort and
diarrhea.
2. Urticaria rash
3. Reversible hearing loss especially in high doses.
4. Headache.
5. Drowsiness
6. Cholestatic jaundice has been reported following prolonged use of Erythromycin

Drug interactions

1. Erythromycin inhibits cytochrome P450 and causes accumulation of theophylline,

warfarin and terfenadine. This can result in clinically important adverse effects.
2. Macrolide antibiotics interact with Chloramphenicol because they compete for the
same receptors at the 50s ribosomal subunits.
Note: Cytochrome P450 enzymes are essential for the metabolism of many medications.
Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs.

Contraindications of Macrolide Antibiotics

 All Macrolide antibiotics are contraindicated in Liver impairement
 Confirmed or reported allergic reactions with Macrolide antibiotics.

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