MACROLIDES
MACROLIDES
Structure:
- Large cyclic lactone ring structure with attached sugars.
Drugs included:
- Erythromycin, azithromycin, roxithromycin, fidaxomicin, tacrolimus & clarithromycin.
- Tacrolimus –
- An immunosuppressant drug.
- FK-506 commonly known as Tacrolimus.
MOA:
- Drugs bind to 50S ribosome & block peptide chain translocation from A to P site.
- Ketolides & lincosamides have similar mechanism of action.
Pharmacokinetics:
- Well absorbed orally.
- Drug excretion:
- Excreted by biliary route – Erythromycin.
- Excretion of urinary excretion – Azithromycin.
- Excreted by both renal & biliary routes – Clarithromycin.
- Half-life:
- Azithromycin – Longest half-life; hence, administered as single daily dose.
- Note: Erythromycin requires administered four times a day.
General drug effects:
- An anti-inflammatory action:
- Due to effect on neutrophils & inflammatory cytokines.
- Hence, used in prevention of cystic fibrosis exacerbation.
Clinical Uses:
- DOC for Chancroid by Haemophilus ducreyi – Azithromycin (single dose).
- DOC for treatment of toxoplasmosis in pregnancy – Spiramycin.
- Against Corynebacterium (diphtheria), Campylobacter, Legionella infections, Atypical pneumonia, Whooping cough by Bordetella pertussis – As second choice drugs to penicillins.
- For treatment of C. difficile infection – Fidaxomicin.
- Used in prevention of cystic fibrosis exacerbation.
Individual drugs:
1. Azithromycin:
- More active against H. influenza & Neisseria.
- Long half-life – hence, single dose is effective.
- Not an enzyme inhibitor & free from drugs interactions.
- Uses:
- For treatment of urogenital infections, caused by chlamydia.
- For prophylaxis of MAC infections – once weekly.
2. Roxithromycin:
- Similar spectrum as of azithromycin.
3. Clarithromycin:
- Useful for prophylaxis & treatment of Mycobacterium avium complex.
- Treatment of peptic ulcer by H. pylori.
4. Fidaxomicin:
- Non-absorbed macrolide.
5. Tacrolimus:
- Indicated for prophylaxis of organ transplant rejection.
- Glucose intolerance – Well-recognized side effect.
General adverse effects:
- Gastro-intestinal effects – Most common for all macrolides.
Macrolide Toxicity:
- Mainly by Erythromycin.
- Erythromycin estolate implicated to cause acute cholestatic hepatitis, especially in pregnant females. Other salts of erythromycin are safe.
MOA: Erythromycin, roxithromycin & clarithromycin inhibit CYP3A4.
Toxicity effects:
- On administered to patients receiving terfenadine, astemizole or cisapride (substrates of CYP3A4):
- Lead to QT interval prolongation & serious polymorphic ventricular tachycardia (torsades de pointes).
- Intravenous erythromycin (not oral) – Cause dose-dependent reversible ototoxicity.
Other effects:
- Diarrhea – Due to motilin receptors stimulation.
Drug interactions:
- Erythromycin increases plasma theophylline concentration, by inhibiting CYP1A2.
Exam Important
- Erythromycin, azithromycin, roxithromycin, fidaxomicin, tacrolimus & clarithromycin are all macrolides.
- Erythromycin is given in decreased bowel motility (diarrhea) because it binds to motilin receptors stimulation.
- Tacrolimus is an immunosuppressant drug.
- Macrolides bind to 50S ribosome & block peptide chain translocation from A to P site.
- Azithromycin has longest half-life; hence, administered as single daily dose.
- Due to their anti-inflammatory action, macrolides are used in prevention of cystic fibrosis exacerbation.
- DOC for Chancroid by Haemophilus ducreyi is azithromycin (single dose).
- DOC for treatment of toxoplasmosis in pregnancy is Spiramycin.
- Macrolides are also effective against Corynebacterium (diphtheria), Campylobacter, Legionella infections, Atypical pneumonia, Whooping cough by Bordetella pertussis & are preferred as second choice drugs to penicillins.
- Macrolide antibiotic that is used for treatment of C. difficile infection is Fidaxomicin.
- Azithromycin is macrolide antibiotic more active against H. influenza & Neisseria.
- Azithromycin has a longer half-life & its single dose is effective.
- Azithromycin is not an enzyme inhibitor & free from drugs interactions.
- Erythromycin estolate implicated to cause acute cholestatic hepatitis, especially in pregnant females.
- Erythromycin, roxithromycin & clarithromycin inhibit CYP3A4.
- Erythromycin on administering to patients receiving terfenadine, astemizole or cisapride (substrates of CYP3A4), can lead to QT interval prolongation & serious polymorphic ventricular tachycardia (torsades de pointes).
- Intravenous erythromycin can cause dose-dependent reversible ototoxicity.
- Erythromycin increases plasma theophylline concentration, by inhibiting CYP1A2.
- Fk-506 is a macrolide antibiotic.
- FK-506 commonly known as Tacrolimus.
- Tacrolimus is indicated for prophylaxis of organ transplant rejection & its well-recognized side effect is glucose intolerance.
Don’t Forget to Solve all the previous Year Question asked on MACROLIDES