Macrolides
Dr. Tejas K. Patel
Asst. Professor,
Department of Pharmacology,
GMERS Medical College, Gotri,
Vadodara
1/15/16
Macrolides
Erythromycin
Roxithromycin
Clarythromycin
Azithromycin
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Erythromycin
Isolated from streptomyces erythreus
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Mechanism of action
Acts by protein synthesis inhibition
Bacteriostatic at low concentration
Bactericidal at high concentration
Cidal action depends on
organisms concerned
Rate of multiplication
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Mechanism of action
Ribosomes are involved in protein
synthesis
Bacterial ribosomes consists of 50s
and 30s subunits
which combines to form 70s
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-lactam antibiotics
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-lactam antibiotics
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-lactam antibiotics
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-lactam antibiotics
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Mechanism of resistance
Modification of receptor (target) site
on 50s ribosome subunit
Alteration in permeability of
antibiotic
Efflux mechanism
Elaboration of esterase enzyme that
hydrolyze macrolides
Cross resistance seen between
macrolides and also with
clindamycin and chloramphenicol
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Pharmacokinetics
Absorption
Acid labile: Inactivated by gastric HCL
Enteric coated tablets
Acid stable esters available
Erythroycin stearate
Erythroycin estolate
Erythroycin ethylsucccinate
Distribution
Widely distributed into most tissues, except the brain
and CSF
Cross the placental barrier
Metabolism
Partly metabolized in liver and actively secreted in bile
(major route of excretion )
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Plasma half life: 1.5 hr
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Adverse effects
Remarkably safe drug
Gastointestinal ADRs
Mild to moderate epigastric pain
Diarrhoea
Due to stimulation of motilin receptor in GIT
Ototoxicity
Reversible hearing impairment on very
high doses
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Cholestatic hepatitis
High incidence in pregnant women
Mainly due to hypersensitivity to
estolate ester and not due to
erythromycin
Rarely allergic reactions
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Drug interactions
Erythromycin inhibits metabolism of
many drugs
Rise in plasma levels of theophyllin,
carbamazepine, phenytoin, warfarin
Prolong QT interval and serious
ventricular arrythmia
Due to inhibition of metabolism of
terfenadine, astemizole, cisapride
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Spectrum
Gm+ve cocci
Sterp. Pyogenes
Strep. Pneumoniae
Strep. Viridans
Staph. aureus
( PRSA)
Gm-ve cocci
N. Gonorrhoea
N. Meningitidis
Moraxella catarrhalis
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Gm+ve bacilli
C. diphtheriae
Clostridia
Bacillus anthracis
Listeria
monocytogenes
Spirochates
T. Pallidum
Leptospirae
Pharmacovigilance
Spectrum
Miscellaneous
Gm-ve bacilli
Bordetella pertussis
Bartonella henselae
Campylobacter
jejuni
Legionella
pneumophila
H. Influenzae
H. ducreyi
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Mycoplasma
pneumoniae
Ureaplasma
urealyticum
Gard. Vaginalis
Chlamydia
trachomatis
Chlamydia
Pneumoniae
Chlamydia psittaci
Pharmacovigilance
Not effective against
Enterobacteriae
Pseudomonas
Salmonella, Shigella
Bacteroid fragilis
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Therapeutic uses
Dose: 250-500 mg QDS
Alternative to penicillin in allergic pts
Streptococcal pharyngitis, tonsillitis,
mastoiditis, community acquired respiratory
infection
Prohylaxis of SABE & rhematic fever
Diptheria
Tetanus
Syphilis and gonorrhoea
Leptospirosis
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First choice drug for
Atypical pneumonia caused by mycoplasma
pneumonia
Whooping (Pertussis)
1-2 wk course
Incubation period
disease is prevented
Catarrhal stage (1 wk)
Abort the next stage or reduce the severity
Paroxysmal stage (2-4 wks)
Only eradicate the organism
No effect on duration & severity of croup
Convalscent stage (4-12 wks)
Not modified
Chancroid (as good as azithromycin/ceftriaxone)
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As a 2nd choice
Campylobacter gastroenteritis
Ciprofloxacin
Legionnaires pneumonia
Azithro or cipro
Chlamydial conjunctivitis and urethritis
Azithro single dose preferred
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Non-antimicrobial uses
Diabetic gastroperesis
Useful in management of rheumatoid
arthritis, cystic fibrosis, chronic sinusitis,
asthma
It has anti-inflammatory effects by proinflammatory
cytokines release from
phagocytes
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Roxithromycin
Semi synthetic long acting acid stable
macrolide
Antimicrobial spectrum same as erythromycin
It is more potent against Moraxella catarrhalis,
Legionella pneumophila, Gard. Vaginalis
Less active against Bordetella pertussis
Good oral absorption
Longer Half life 12 hr
Better gastric tolerability
Drug interactions are less
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Dose: 150 mg 12 hrly interval
Therapeutic uses
Similar to erythromycin
More preferred in otitis media, sinusitis
and pneumonia caused by Moraxella
catarrhalis and Legionella pneumophila
Genital tract infection
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Clarythromycin
Semi synthetic derivative
Acid stable
Food delay but does not interfere with its
oral absorption
Widely distributed, except brain and CSF
Metabolized by saturation kinetics
Half life: 3-6 hr at low dose & 6-9 hr on high dose
Active metabolite
Better gastric tolerance
Drug interactions are same as erythromycin
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Same spectrum as erythromycin
It is more potent against
Moraxella catarrhalis,
Legionella pneumophila,
H. Influenzae, H. Pylori,
Mycoplasma pneumoniae,
Mycobacterium avium complex and
intracellular,
Mycobacterium leprae,
Toxoplasma
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Therapeutic uses
Sinusitis, otitis media
Atypical pneumonia
Exacerbation of chronic bronchitis due
to H. Influenzae
Peptic ulcer caused by H. Pylori
amoxycillin 1 g +Clarythromycin 500 mg+
omeprazole 20 mg BD for 14 days
MAC infection in AIDS
Toxoplasmosis
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Azithromycin
Congener of erythromycin
Has extended spectrum
Improved pharmacokinetics
Better tolerability
Better drug interaction profile
Once a day dosing
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Extended spectrum compared to
erythromycin
It is more potent against
N. Gonorrhoeae,
Moraxella catarrhalis,
Legionella pneumonia, H. Influenzae, H.
ducryi, Campylobacter jejuni,
Calymmatobacterium granulomatis,
Mycoplasma pneumonia, Chlamydia
Mycobacterium avium complex
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Therapeutic uses
Pharyngitis, tonsilitis, Sinusitis, otitis media
Exacerbation of chronic bronchitis
Legionaires pneumonia
500 mg OD oral for 2 wks
Chlamydia infections
Non specific urethritis, cervicitis
Lymphogranuloma venerum,
Trachoma in eye
Chlamydia Pneumonia
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Donovanosis (Granuloma inguinale)
500 mg OD for 7 days
Chanchroid and Gonorrhoea (PPNG)
1 g OD single dose
MAC infection in AIDS
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