Pharmacology
Central Nervous System
Regarding paracetamol, which of the following statements is CORRECT:
Answer:
Paracetamol is a non-opioid analgesic, similar in efficacy to aspirin, with antipyretic properties but no anti-inflammatory properties. It is well absorbed orally and does not cause gastric irritation. Paracetamol is a suitable first-line choice for most people with mild-to-moderate pain, and for combination therapy.Paracetamol
Pharmacology / Central Nervous System
Last Updated: 1st May 2023
Mechanism of Action
Paracetamol is a non-opioid analgesic, similar in efficacy to aspirin, with antipyretic properties but no demonstrable anti-inflammatory properties. It is well absorbed orally and does not cause gastric irritation. Paracetamol is a suitable first-line choice for most people with mild-to-moderate pain, and for combination therapy.
Contraindications and Cautions
There are no contraindications to the use of paracetamol.
Paracetamol should be used with caution in:
- Alcohol dependence
- Dehydration
- Chronic malnutrition
- Hepatic impairment
- People who weigh < 50 kg
Side Effects
Adverse effects are rare with paracetamol. However, paracetamol doses greater than the maximum daily dose of 4 grams can lead to hepatotoxicity (and, less frequently, acute kidney injury). In some people this may be fatal.
Overdose
Overdose with acetaminophen results in accumulation of a minor metabolite, N-acetyl-p-benzoquinone, which is responsible for hepatotoxicity. When the enzymes for glucuronide and sulfate conjugation of acetaminophen and the reactive metabolite become saturated, an alternative glutathione conjugation pathway (cytochrome P-450 dependent) becomes more important. If hepatic glutathione is depleted, such as may occur with alcohol consumption, the reactive metabolite accumulates and may cause hepatic damage by interaction with cellular macromolecules, such as DNA and RNA.
People who have taken an overdose of paracetamol (accidentally or intentionally) may require urgent admission to hospital, depending on the quantity of paracetamol taken and the presence of risk factors for liver damage, including: alcohol dependence, pre-existing liver disease, malnutrition, and the use of liver enzyme inducing drugs (such as rifampicin, carbamazepine, and phenytoin).
Early symptoms of paracetamol toxicity are nausea, vomiting, and abdominal pain which usually settle within 24 hours. Symptoms of liver damage include right subcostal pain and tenderness. Liver damage peaks 3 to 4 days after paracetamol ingestion. The person may develop encephalopathy, bleeding, hypoglycaemia, and cerebral oedema.
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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 |
