Pharmacology
Cardiovascular
A patient requires antibiotic treatment for an infection. You are aware that the patient is on long-term statin therapy. Which of the following antibiotics may increase the risk of myopathy in this patient:
Answer:
There is an increased incidence of myopathy if a statin is given with a fibrate, with lipid-lowering doses of nicotinic acid, with fusidic acid, or with drugs that increase the plasma-statin concentration, such as macrolide antibiotics (erythromycin and clarithromycin), imidazole and triazole antifungals, and ciclosporin; close monitoring of liver function and, if muscular symptoms occur, of creatine kinase is necessary.Statins
Pharmacology / Cardiovascular
Last Updated: 17th April 2019
Statins may be used for primary or secondary prevention of cardiovascular disease and for treatment of primary or familial hypercholesterolaemia.
Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration.
Mechanism of Action
Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis. Inhibition of HMG CoA reductase reduces low-density lipoprotein (LDL) cholesterol levels by slowing down the production of cholesterol in the liver and increasing the liver's ability to remove the LDL cholesterol already in the blood.
Indications
Statins should be offered to all patients, including the elderly, with cardiovascular disease such as those with coronary heart disease (including history of angina or acute myocardial infarction) or occlusive arterial disease (including peripheral vascular disease, non-haemorrhagic stroke, or transient ischaemic attacks). The use of statins should be considered in patients with a high risk of developing cardiovascular disease (primary prevention) which can be assessed using risk calculators.
Contraindications
Statins should be avoided in:
- People with active liver disease
- People with transaminase (alanine aminotransferase or aspartate aminotransferase) levels that are three or more times the upper limit of normal
- Pregnant or breastfeeding women (discontinue 3 months before attempting to conceive)
Cautions
Statins should be used with caution in people:
- With a history of liver disease
- Who consume high level of alcohol
- With predisposing factors for rhabdomyolysis such as older age (> 70 years), concomitant use with an interacting drug, renal impairment, hypothyroidism, and personal or familial history of hereditary muscular disorders
Side Effects
Adverse effects of statins include:
- Headache
- Epistaxis
- Gastrointestinal disorders (such as constipation, flatulence, dyspepsia, nausea, and diarrhoea)
- Musculoskeletal and connective tissue disorders (such as myalgia, arthralgia, pain in the extremity, muscle spasms, joint swelling, and back pain)
- Hyperglycaemia and diabetes
- Myopathy and rhabdomyolysis
- Interstitial lung disease
- Hepatotoxicity
Muscle Effects
The risk of myopathy, myositis, and rhabdomyolysis associated with statin use is rare. Although myalgia has been reported commonly in patients receiving statins, muscle toxicity truly attributable to statin use is rare.
Muscle toxicity can occur with all statins, however the likelihood increases with higher doses and in certain patients. Statins should be used with caution in patients at increased risk of muscle toxicity, including those with a personal or family history of muscular disorders, previous history of muscular toxicity, a high alcohol intake, renal impairment or hypothyroidism.
There is an increased incidence of myopathy if a statin is given with a fibrate, with lipid-lowering doses of nicotinic acid, with fusidic acid, or with drugs that increase the plasma-statin concentration, such as macrolide antibiotics (erythromycin and clarithromycin), imidazole and triazole antifungals, and ciclosporin; close monitoring of liver function and, if muscular symptoms occur, of creatine kinase is necessary.
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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 |
