Mechanism of Action of Erythromycin

Introduction

Erythromycin is a macrolide antibiotic widely used in the treatment of infections caused by gram-positive cocci, atypical pathogens, and certain gram-negative organisms. It is a bacteriostatic agent that inhibits bacterial protein synthesis and serves as an important alternative in patients allergic to penicillin. From an exam perspective, erythromycin is high-yield due to its ribosomal binding site, drug interactions, and characteristic adverse effects.

Mechanism of Action (Step-wise)

Erythromycin inhibits bacterial protein synthesis by acting at the ribosomal level.

Step 1: Entry into bacterial cell
Erythromycin penetrates susceptible bacteria and reaches the ribosomal machinery.

Step 2: Binding to 50S ribosomal subunit
It binds reversibly to the 23S rRNA of the 50S ribosomal subunit.

Step 3: Inhibition of translocation
Erythromycin blocks the translocation step during protein elongation, preventing movement of the growing peptide chain from the A site to the P site.

Step 4: Suppression of protein synthesis
Inhibition of translocation halts bacterial protein synthesis, leading to impaired bacterial growth.

Step 5: Bacteriostatic effect
At usual therapeutic concentrations, erythromycin is bacteriostatic, though it may be bactericidal against highly sensitive organisms at high concentrations.

Pharmacokinetics

• Route of administration: Oral, IV, topical
• Oral absorption: Acid-labile (enteric-coated or ester forms used)
• Distribution: Widely distributed; poor CNS penetration
• Protein binding: High
• Metabolism: Hepatic (potent CYP3A4 inhibitor)
• Half-life: ~1.5–2 hours
• Excretion: Mainly via bile; small amount in urine

Clinical Uses

• Respiratory tract infections (Streptococcus pneumoniae, Mycoplasma pneumoniae)
• Atypical pneumonia (Mycoplasma, Chlamydia, Legionella)
• Diphtheria (alternative to penicillin)
• Pertussis
• Chlamydial infections
• Acne vulgaris (topical use)
• Gastroparesis (prokinetic action via motilin receptor stimulation)

Adverse Effects

Gastrointestinal:

• Nausea, vomiting
• Abdominal cramps
• Diarrhea (motilin receptor stimulation)

Hepatic:

• Cholestatic hepatitis (especially with estolate form)

Cardiac:

• QT interval prolongation
• Risk of torsades de pointes

Drug interactions:

• Increased levels of theophylline, warfarin, carbamazepine, statins (CYP3A4 inhibition)

Comparative Analysis

Erythromycin vs Azithromycin vs Clarithromycin

Explanation:
Erythromycin is associated with significant gastrointestinal intolerance and drug interactions due to strong CYP3A4 inhibition. Newer macrolides such as azithromycin offer improved tolerability and longer half-lives, making them preferable in many clinical situations.

MCQs

1. Erythromycin inhibits bacterial protein synthesis by binding to:
   a) 30S ribosomal subunit
   b) 40S ribosomal subunit
   c) 50S ribosomal subunit
   d) DNA gyrase

Answer: c) 50S ribosomal subunit

2. The specific step inhibited by erythromycin is:
   a) Initiation
   b) Peptide bond formation
   c) Translocation
   d) Termination

Answer: c) Translocation

3. Erythromycin is primarily bacteriostatic because it:
   a) Disrupts cell wall synthesis
   b) Inhibits folate metabolism
   c) Inhibits protein synthesis
   d) Causes DNA damage

Answer: c) Inhibits protein synthesis

4. Which enzyme system is inhibited by erythromycin?
   a) CYP2C9
   b) CYP1A2
   c) CYP3A4
   d) MAO

Answer: c) CYP3A4

5. Prokinetic action of erythromycin is due to stimulation of:
   a) Dopamine receptors
   b) Serotonin receptors
   c) Motilin receptors
   d) Histamine receptors

Answer: c) Motilin receptors

6. Which adverse effect is characteristic of erythromycin?
   a) Nephrotoxicity
   b) Ototoxicity
   c) QT prolongation
   d) Bone marrow suppression

Answer: c) QT prolongation

7. Erythromycin estolate is associated with:
   a) Renal failure
   b) Cholestatic hepatitis
   c) Hemolysis
   d) Photosensitivity

Answer: b) Cholestatic hepatitis

8. Compared to azithromycin, erythromycin has:
   a) Longer half-life
   b) Less GI intolerance
   c) More drug interactions
   d) Better gram-negative coverage

Answer: c) More drug interactions

9. Which organism is classically treated with erythromycin?
   a) Pseudomonas aeruginosa
   b) Mycoplasma pneumoniae
   c) Mycobacterium tuberculosis
   d) Proteus mirabilis

Answer: b) Mycoplasma pneumoniae

10. Erythromycin resistance most commonly occurs due to:
    a) Efflux pumps
    b) Enzyme activation
    c) Alteration of ribosomal binding site
    d) Increased permeability

Answer: c) Alteration of ribosomal binding site

FAQs

1. Why is erythromycin considered bacteriostatic?
It inhibits protein synthesis without directly killing bacteria.

2. Why is erythromycin poorly tolerated gastrointestinally?
Due to stimulation of motilin receptors in the gut.

3. Can erythromycin be used in penicillin allergy?
Yes, it is a common alternative.

4. Why does erythromycin cause drug interactions?
Because it strongly inhibits CYP3A4.

5. Is erythromycin effective against atypical organisms?
Yes, especially Mycoplasma, Chlamydia, and Legionella.

References

• Goodman & Gilman’s The Pharmacological Basis of Therapeutics
  https://accesspharmacy.mhmedical.com
• Katzung BG. Basic and Clinical Pharmacology
  https://accessmedicine.mhmedical.com
• Tripathi KD. Essentials of Medical Pharmacology
• Harrison’s Principles of Internal Medicine
  https://accessmedicine.mhmedical.com

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