macrolides

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Faculty of Pharmacy
Macrolide Antibiotics
At the end of this lecture, the student will be able to:
• Describe the mechanism of action of macrolide
antibiotics
• Outline the pharmacokinetics of macrolides
• Explain the clinical uses of macrolides

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Faculty of Pharmacy
Contents
Macrolide antibiotics
• Mechanism of action
• Mechanism of resistance
• Pharmacokinetics
• Adverse effects
• Clinical uses

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Faculty of Pharmacy
Macrolides
• Multimembered lactone ring structure
• One or more deoxysugar molecules are attached
• Prototype – Erthromycin – 14 membrane lactone ring
attached with deoxysugar moiety
• Derived from Streptomyces erythreus
• Roxithromycin, clarithromycin and azithromycin –
semisynthetic derivatives of erythromycin

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Faculty of Pharmacy
©M. S. Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Macrolides
• Erythromycin
• Roxithromycin
• Clarithromycin
• Spiramycin
• Azithromycin
• Oleandomycin
• Troleandomycin

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Faculty of Pharmacy
Mechanism of Action
• Inhibits protein synthesis
• Broad spectrum antibiotics but more active against gram
positive
• Low concentration – Bacteriostatic
• High concentration – Bactericidal
• Binds to 50s ribosomal subunit
• Inhibit translocation of peptide chain

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Faculty of Pharmacy
Mechanism of Action
• Enter organism by active transport
• Entry is favored at alkaline pH
• Remain unionised at alkaline pH
• Penetration is 100 times more at alkaline pH
• Inhibits the action of action of chloramphenicol
• No affinity to mammalian ribosomes

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Faculty of Pharmacy
Mechanism of Action

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Faculty of Pharmacy
Mechanism of Resistance
• Presence of efflux pumps
• Ribosomal protection by enzyme – methylase
• Drug hydrolysis by esterase
• Chromosomal mutations altering 50s subunit

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Faculty of Pharmacy
Mechanism of Resistance

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Faculty of Pharmacy
Antimicrobial Spectrum
• Similar to that of β- lactam antibiotics
• Used as substitute for penicillins
• Gram positive organisms
– Streptococcus pneumoniae
– Streptococcus pyogenes
– Cornybacterium diptheriae
– Clostridium tetanii
• Gram negative organism
– Nesseria gonorrhea
– N. meningitis
– H. influenzae
– H. pylori

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Faculty of Pharmacy
Adverse Effects
• Available as Erthromycin base, Erythromycin estolate,
Erythromycin ethyl succinate and Stearate
• Oral – large dose – GI problems
• Erythromycin estolate – Cholestatic jaundice
• i.v- high dose – transient auditory impairment
• Infants – hypertonic pyloric stenosis
• Other macrolides causes minor GIT upsets

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Faculty of Pharmacy
Pharmacokinetics – Erythromycin
• Available as base and ester
• Ester used in oral formulations
• Parenteral - Erythromycin gluceptate and lactobionate
• i.m – pain
• Absorbed from upper part of small intestine
• Food interferes with absorption
• Incomplete absorption

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Faculty of Pharmacy
Pharmacokinetics – Erythromycin
Distribution
• Good but not in CSF
• Therapeutic concentration attained in tonsils, middle ear
fluid, lungs, prostrate fluid
Metabolism – liver
Excretion
• Major – bile
• Small amount – Urine
• Plasma half life – 1.5 h

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Faculty of Pharmacy
Pharmacokinetics
• Long acting
• Half life 12h; acid stable
• Better absorbed and good tissue
penetration
Roxithromycin
• Acid stable
• High concentration attained in prostrate,
lungs, stomach and inflammatory cells
Azithromycin
• Long acting; acid stable
• Wide distribution
• 60-70% protein bound
Clarithromycin

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Faculty of Pharmacy
Clinical Uses

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Faculty of Pharmacy
Clinical Uses
Erythromycin
• Streptococcal and pneumococcal infections
• Respiratory, neonatal and genital infection caused by clamydia
• Alternate drug for syphillis and gonorrhea
• Prophylactic for recurrence of rheumatic fever

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Faculty of Pharmacy
Clinical Uses
Roxithromycin
• Substitute of erythromycin in pharyngitis, tonsilitis, sinusitis,
acute bronchitis & pneumonia
Azithromycin
• Respiratory tract infection
• Urogenital infection
Clarithromycin
• Upper and lower respiratory tract infection

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Faculty of Pharmacy
Summary
• Macrolides are multimembered lactone ring structure
containing one or more deoxysugar molecules
• Inhibits protein synthesis, Binds to 50s ribosomal subunit and
inhibit translocation of peptide chain, Enter organism by
active transport , Entry is favored at alkaline pH
• Therapeutic concentration attained in tonsils, middle ear
fluid, lungs, prostrate fluid; Metabolism – liver ; Excretion –
bile, Urine
• Uses- Streptococcal and pneumococcal infections;
Respiratory, neonatal and genital infection caused by clamydia
• Alternate drug for syphillis and gonorrhea; Prophylactic for
recurrence of rheumatic fever