Pharmacology
Infections
Which of the following side effects is most likely attributed to doxycycline:
Answer:
Tetracyclines most commonly cause gastrointestinal adverse effects such as nausea, vomiting and diarrhoea. Less frequently, they may cause photosensitivity (patients should be advised to avoid exposure to sunlight or sun lamps). At high doses, most tetracyclines can cause hepatic damage. Severe adverse effects are unusual with a short course. However, benign intracranial hypertension has rarely been reported following treatment with a tetracycline; treatment should be discontinued in a patient complaining of headache and visual disturbance.Tetracyclines
Pharmacology / Infections
Last Updated: 26th March 2019
Mechanism of Action
Tetracyclines bind reversibly to the 30S subunit of bacterial ribosomes, preventing the binding of aminoacyl tRNA to the acceptor site on the mRNA–ribosome complex and addition of amino acids to the growing peptide, thus inhibiting bacterial protein synthesis.
The tetracyclines are orally active, broad spectrum antibiotics but increasing bacterial resistance and the development of safer drugs has reduced their usefulness. Absorption from the gut is variable and is reduced by calcium ions (e.g. milk), magnesium ions (e.g. antacids), food and iron preparations. They can also be administered parenterally.
Indications
They remain the treatment of choice for infections caused by chlamydia (trachoma, psittacosis, salpingitis, pelvic inflammatory disease, urethritis, and lymphogranuloma venereum), rickettsia (including Q-fever), brucella (doxycycline with either streptomycin or rifampicin), and the spirochaete, Borrelia burgdorferi (Lyme disease).
They are also used in respiratory and genital mycoplasma infections, in acne and rosacea, in destructive (refractory) periodontal disease, in exacerbations of chronic bronchitis (because of their activity against Haemophilus influenzae), in community acquired pneumonia, and for leptospirosis in penicillin hypersensitivity (as an alternative to erythromycin).
Doxycycline may also used for malaria prophylaxis and as an adjunct to quinine in the treatment of Plasmodium falciparum malaria.
Microbiologically, there is little to choose between the various tetracyclines, the only exception being minocycline which has a broader spectrum but is no longer recommended because of side effects including dizziness and vertigo.
Contraindications
Tetracyclines are contraindicated in children under 12 years (deposition in growing bone and teeth by binding to calcium causes staining and occasionally dental hypoplasia) and in pregnant women (may cause impaired skeletal development and discolouration of teeth). They should also be avoided in people with liver disease, systemic lupus erythematosus, myasthenia gravis and porphyria.
Side Effects
The most common are gastrointestinal adverse effects such as nausea, vomiting and diarrhoea. Less frequently, they may cause photosensitivity (patients should be advised to avoid exposure to sunlight or sunlamps). At high doses, most tetracyclines can cause hepatic damage. Severe adverse effects are unusual with a short course. However, benign intracranial hypertension has rarely been reported following treatment with a tetracycline; treatment should be discontinued in a patient complaining of headache and visual disturbance.
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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 |
