Pharmacology
Central Nervous System
Which of the following is a well recognised adverse effect of metoclopramide:
Answer:
Metoclopramide is commonly associated with extrapyramidal effects and hyperprolactinemia and thus its use must be limited to short-term use. Metoclopramide can induce acute dystonic reactions involving facial and skeletal muscle spasms and oculogyric crises. These dystonic effects are more common in the young (especially girls and young women) and the very old; they usually occur shortly after starting treatment with metoclopramide and subside within 24 hours of stopping it. Injection of an antiparkinsonian drug such as procyclidine will abort dystonic attacks.Antiemetics
Pharmacology / Central Nervous System
Last Updated: 3rd April 2020
Antiemetics should only be prescribed when the cause of the vomiting is known, as otherwise they may delay or mask an underlying diagnosis which should be treated first, particularly in children.
Antihistamines (Histamine-H1 receptor antagonists)
Antihistamines e.g. cyclizine, are effective against nausea and vomiting caused by many different conditions, including motion sickness and vertigo. These agents act by inhibiting histamine pathways, and cholinergic pathways involved in transmission from the vestibular apparatus to the vomiting centre.
There is no evidence that any one antihistamine is superior to another but their duration of action and incidence of adverse effects differ. Adverse effects include drowsiness and antimuscarinic effects such as blurred vision, dry mouth, urinary retention, constipation and confusion.
Phenothiazines
The phenothiazines e.g. prochlorperazine are dopamine-D2 receptor antagonists and act centrally by blocking the chemoreceptor trigger zone. They are of particular use in the treatment of nausea and vomiting caused by neoplastic disease, radiation sickness or by other drugs such as opioids, general anaesthetics, and cytotoxics.
Adverse actions include anticholinergic effects such as drowsiness, dry mouth, and blurred vision, extrapyramidal effects, and postural hypotension. Phenothiazines can all induce acute dystonic reactions such as facial and skeletal muscle spasms and oculogyric crises; children (especially girls, young women, and those under 10 kg) are particularly susceptible.
Some phenothiazines are available as rectal suppositories, which can be useful in patients with persistent vomiting or with severe nausea; prochlorperazine can also be administered as a buccal tablet which is placed between the upper lip and the gum.
Metoclopramide
Metoclopramide is an effective antiemetic and its activity closely resembles that of the phenothiazines (dopamine antagonist); it also acts directly on the gastrointestinal tract as a prokinetic and therefore may be superior in treating nausea associated with gastroduodenal, hepatic and biliary disease. It is contraindicated in gastrointestinal obstruction/perforation.
Metoclopramide is commonly associated with extrapyramidal effects and hyperprolactinemia and thus its use must be limited to short-term use. Metoclopramide can induce acute dystonic reactions involving facial and skeletal muscle spasms and oculogyric crises. These dystonic effects are more common in the young (especially girls and young women) and the very old; they usually occur shortly after starting treatment with metoclopramide and subside within 24 hours of stopping it. Injection of an antiparkinsonian drug such as procyclidine will abort dystonic attacks.
Domperidone acts at the chemoreceptor trigger zone. It has the advantage over metoclopramide hydrochloride and the phenothiazines of being less likely to cause central effects such as sedation and dystonic reactions because it does not readily cross the blood-brain barrier.
Ondansetron
Ondansetron is a serotonin-5HT3 receptor antagonist which acts both at the chemoreceptor trigger zone and peripherally. Because it has fewer unwanted actions, it is widely used to prevent or reduce nausea or vomiting associated with cancer chemotherapy and general anaesthesia. The most common adverse effects of these drugs are headache and mild constipation.
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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 |
