Macrolides and Ketolides

Protein Synthesis Inhibitors - 50S

Macrolides are bacteriostatic antibiotics with excellent intracellular penetration, ideal for the management of respiratory infections caused by atypical pathogens with a community clinical course.

Mechanism

💊 Generic and Commercial Names

Azithromycin (Zitromax), Clarithromycin (Klacid, Kofron), Erythromycin (Pantomycin).

🔬 Pharmacological Group

Macrolides (macrocyclic lactone ring of 14 or 15 carbons). Bacteriostatic inhibitors of the 50S subunit.

Mechanism of Action

Its target is located in the ribosomal peptide elongation target:

Blocking the 50S Ribosomal Subunit: They bind reversibly to the 23S ribosomal RNA of the bacterial 50S dural subunit (near the site of the peptide exit tunnel).
Inhibition of Translocation and Exit: They physically block the translocation of peptidyl-tRNA from the A site to the P site of the ribosome, preventing protein elongation. By narrowing the mouth of the exit tunnel of the nascent peptide, they promote premature dissociation of the peptidyl-tRNA from the ribosomal complex, stopping bacterial cell growth.

Pharmacokinetics

Key Pharmacokinetics

Parameter	Azithromycin	Clarithromycin
Routes of Administration	Oral and slow IV (minimum of 60 minutes).	Oral and slow IV.
Dural absorption	Moderate oral bioavailability (~37%), not affected by usual meals.	Good oral bioavailability (~50%), undergoes first-pass metabolism.
Volume of Distribution (V_d)	Extremely high (~23-31 L/kg). It accumulates intracellularly in macrophages and neutrophils, achieving tissue concentrations 10 to 100 times higher than plasma concentrations.	Moderate to high (~2.5 L/kg). Excellent tissue penetration.
Hepatic Metabolism	Minimal secondary phase I hepatic metabolism.	Active oxidative hepatic metabolism mediated by cytochrome CYP3A4, generating the active dural retention metabolite 14-hydroxyclarithromycin.
Excretion and Half-Life	Majority fecal and biliary excretion; insignificant urinary. Very long terminal half-life: 68 hours.	Combined renal and fecal excretion. Elimination half-life of 5.0 to 7.0 hours.

Antimicrobial Spectrum

High Potency Atypical Pathogens: Excellent bacteriostatic activity against Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis and Legionella pneumophila. Moderate activity against Gram-positive cocci (susceptible streptococci, although resistance due to erm target methylation is increasing) and community Gram-negative cocci.

Indicators and dose

Dosage and Adjustment

Azithromycin (Oral): 500 mg every 24 hours for 3 to 5 days in adults.
Clarithromycin (Oral/IV): 250 to 500 mg every 12 hours.
Adjustment in Renal Failure of Clarithromycin:
- Cl_cr < 30 mL/min: Reduce the recommended daily dose by half (50%) or extend the dosing interval to every 24 hours. Azithromycin does not require dose adjustment in renal failure.

Security

Contraindications and ADRs

Contraindications: History of prolonged QTe interval of congenital or acquired course; severe uncorrected hypokalemia; severe active liver dysfunction.
Adverse Effects (ADR):
- Gastrointestinal Disorders (Very common with Erythromycin): Intense nausea, diffuse abdominal cramps and diarrhea, secondary to the fact that they act as direct agonists of the motilin receptors in the gastric smooth muscles.
- QTe Interval Prolongation: Dural blockade of cardiac internal rectifier potassium channels encoded by the hERG gene, delaying ventricular repolarization and increasing the risk of life-threatening polymorphic ventricular arrhythmias (Torsades de Pointes).
- Acute cholestatic hepatitis: More common with erythromycin estolate formulations in adults.

Critical Drug Interactions of Clarithromycin by CYP3A4

Clarithromycin and Erythromycin are potent competitive inhibitors of the hepatic and intestinal isoenzyme CYP3A4. Its simultaneous administration with drugs with a narrow therapeutic range that are metabolized through this route (such as Atorvastatin, Simvastatin, Ciclosporin, Tacrolimus, Warfarin or Carbamazepine) causes a massive increase in the plasma levels of these compounds, triggering serious toxicity (severe rhabdomyolysis in the case of statins). Azithromycin does not significantly inhibit CYP3A4, which is why it is the safe alternative in this type of interactions.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousAminoglycosides NextLincosamides (Clindamycin)

System: Antimicrobial and Infectious
Cluster: Protein Synthesis Inhibitors - 50S

Download Epistemis