Pharmacology
Infections
A 75 year old man presents to the Emergency Department with a 3 day history of scrotal pain and swelling. You suspect epididymo-orchitis, likely due to an enteric organism, and prescribe ofloxacin. What is the mechanism of action of quinolone antibiotics:
Answer:
Quinolones interfere with bacterial nucleic acid synthesis.Quinolones
Pharmacology / Infections
Last Updated: 26th March 2019
Mechanism of Action
Quinolones interfere with bacterial nucleic acid synthesis. Ciprofloxacin is well absorbed orally and can be given intravenously. It is eliminated mainly by the kidneys.
Indications
Ciprofloxacin is active against both Gram-positive and Gram-negative bacteria. It is particularly active against Gram-negative bacteria, including salmonella, shigella, campylobacter, Neisseria, and pseudomonas. Ciprofloxacin has only moderate activity against Gram-positive bacteria such as Streptococcus pneumoniae and Enterococcus faecalis; it should not be used for pneumococcal pneumonia. It is active against chlamydia and some mycobacteria. Most anaerobic organisms are not susceptible.
Ciprofloxacin can be used for respiratory tract infections (but not for pneumococcal pneumonia), urinary tract infections (including acute pyelonephritis and prostatitis), biliary tract infections, infections of the gastrointestinal system (including typhoid fever), bone and joint infections, gonorrhoea and septicaemia caused by sensitive organisms.
CSM Advice
The CSM has warned that quinolones may induce convulsions in patients with or without a history of convulsions; taking NSAIDs at the same time may predispose to this. Convulsions may occur because the quinolones are GABA antagonists.
Tendon damage (including rupture) has also been reported rarely in patients taking quinolones, typically occurring within 48 hours of starting treatment. Quinolones are therefore contraindicated in patients with a history of tendon disorders related to quinolone use and should be used with caution in patients over 60 years of age (who are more prone to tendon damage) and in those taking concomitant corticosteroids (which also predispose to tendon damage). If tendinitis is suspected, the quinolone should be stopped immediately.
Contraindications
Quinolones are contraindicated in patients with a history of tendon disorders related to quinolone use.
Quinolones should be used with caution in:
- conditions that prolong the QT interval (including electrolyte disturbance)
- concomitant use with other drugs known to prolong the QT interval
- epilepsy or conditions that predispose to seizures
- G6PD deficiency
- myasthenia gravis
- renal impairment (reduce dose)
- children/adolescents (may be at risk of arthropathy)
Side Effects
Common side effects include diarrhoea, dizziness, headache, nausea and vomiting.
Ciprofloxacin can occasionally cause drowsiness and may impair the performance of skilled tasks such as driving.
Other adverse effects include:
- Tendon damage (including rupture)
- Seizures (in patients with and without epilepsy)
- QT-interval prolongation
- Photosensitivity
- Antibiotic-associated colitis
Interactions
Ciprofloxacin increases plasma concentrations of theophylline.
There is an increased risk of convulsions when quinolones are given with NSAIDs or theophylline.
There is an increased risk of tendon damage when quinolones are given with corticosteroids.
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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 |
