Pharmacology
Infections
What is the mechanism of action of macrolide antibiotics:
Answer:
Erythromycin inhibits protein synthesis by binding irreversibly to the bacterial 50S ribosomal subunit. It inhibits aminoacyl translocation and the formation of initiation complexes.Macrolides
Pharmacology / Infections
Last Updated: 26th March 2019
The macrolides have an antibacterial spectrum that is similar but not identical to that of benzylpenicillin (i.e. narrow spectrum, mainly active against Gram-positive organisms); they are thus an alternative in penicillin-allergic patients or for penicillin-resistant staphylococci. However, they are not effective in meningitis because they do not penetrate the CNS adequately.
Macrolides are usually given orally, but erythromycin and clarithromycin can be given intravenously if necessary.
Mechanism of Action
Erythromycin inhibits protein synthesis by binding irreversibly to the bacterial 50S ribosomal subunit. It inhibits aminoacyl translocation and the formation of initiation complexes.
Indications
Indications for the macrolides include campylobacter enteritis, respiratory infections (including pneumonia, whooping cough, Legionella, chlamydia, and mycoplasma infection), Lyme disease and skin infections. Erythromycin is also used in the treatment of early syphilis, uncomplicated genital chlamydial infection, and non-gonococcal urethritis but has poor activity against Haemophilus influenzae.
Clarithromycin is an erythromycin derivative with slightly greater activity than the parent compound. Tissue concentrations are higher than with erythromycin. It is given twice daily. Clarithromycin is also used in regimens for Helicobacter pylori eradication.
Cautions
Erythromycin is metabolised by the liver and dosage reduction in renal failure is usually unnecessary unless the renal failure is severe. Macrolides are very safe drugs.
Macrolides should be used with caution in myasthenia gravis, hepatic impairment or in electrolyte disturbances or conditions that predispose to QT-interval prolongation (as macrolides themselves can cause QT-interval prolongation).
Side Effects
Macrolides commonly cause nausea, vomiting, diarrhoea, and abdominal discomfort. Gastrointestinal side effects are mild and less frequent with azithromycin and clarithromycin than with erythromycin.
Less common side effects include hepatotoxicity, cholestatic jaundice, rash, reversible hearing loss (sometimes with tinnitus). Other adverse effects reported rarely or very rarely include pancreatitis, QT interval prolongation, arrhythmias, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Interactions
Erythromycin and clarithromycin inhibit cytochrome P450-mediated metabolism of warfarin, phenytoin and carbamazepine and may lead to accumulation of these drugs.
There is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) if erythromycin or clarithromycin is taken with atorvastatin or simvastatin.
Erythromycin increases plasma concentrations of theophylline, and theophylline may also reduce absorption of oral erythromycin.
All macrolides can prolong the QT-interval and concomitant use of drugs that prolong the QT interval is not recommended.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
