Pharmacology
Infections
Regarding gentamicin, which of the following statements is INCORRECT:
Answer:
Gentamicin is associated with ototoxicity and nephrotoxicity (acute tubular necrosis) at toxic doses.Aminoglycosides
Pharmacology / Infections
Last Updated: 26th March 2019
Mechanism of Action
Aminoglycosides interfere with bacterial protein synthesis; they bind to the bacterial 30S subunit and inhibit binding of the aminoacyl-tRNA, in addition to causing misreading of the mRNA so that non-functional proteins are synthesised .
Aminoglycosides are active against some Gram-positive and many Gram-negative organisms. The aminoglycosides are not absorbed from the gut and must therefore be given by injection for systemic infections.
Gentamicin is the aminoglycoside of choice in the UK and is used widely for the treatment of serious infections. It has a broad spectrum but is inactive against anaerobes and has poor activity against haemolytic streptococci and pneumococci. When used for the blind therapy of undiagnosed serious infections it is usually given in conjunction with a penicillin or metronidazole (or both).
Indications
Indications include:
- Gram-positive bacterial endocarditis or HACEK endocarditis (in combination with other antibiotics)
- Septicaemia
- Listeria meningitis (with amoxicillin)
- Biliary tract infection
- Peritonitis (with metronidazole or clindamycin)
- Hospital acquired pneumonia
- Surgical prophylaxis
Contraindications
Gentamicin is contraindicated in myasthenia gravis and should be used with caution in renal disease which may result in accumulation and a greater risk of toxic side effects.
Side Effects
The main adverse effects are:
- Ototoxicity (auditory and vestibular damage due to damage to CN VIII)
- Nephrotoxicity (acute tubular necrosis, occurs most commonly in elderly)
- Impaired neuromuscular transmission (may cause a transient myasthenic syndrome)
Serum Monitoring
Gentamicin has a narrow therapeutic index with toxic effects being dose dependent.
Loading and maintenance doses of gentamicin may be calculated on the basis of the patient’s weight and renal function; adjustments are then made according to serum gentamicin concentrations.
Serum concentration monitoring avoids both excessive and subtherapeutic concentrations thus preventing toxicity and ensuring efficacy. Serum-aminoglycoside concentrations should be monitored in patients receiving parenteral aminoglycosides and must be determined in the elderly, in obesity, and in cystic fibrosis, or if high doses are being given, or if there is renal impairment.
In patients with normal renal function, aminoglycoside concentrations should be measured after 3 or 4 doses of a multiple daily dose regimen and after a dose change.
For multiple daily dose regimens, blood samples should be taken approximately 1 hour after intramuscular or intravenous administration (‘peak’ concentration) and also just before the next dose (‘trough’ concentration). If the pre-dose (‘trough’) concentration is high, the interval between doses must be increased. If the post-dose (‘peak’) concentration is high, the dose must be decreased.
For once daily dose regimens, local guidelines on serum concentration monitoring should be consulted.
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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 |
