Abstract
Nausea and vomiting has many causes including drugs, motion sickness, fear, pregnancy, vestibular disease and migraine. In previous decades anaesthesia was almost synonymous with vomiting, but with the advent of new anaesthetic agents and more aggressive treatment the incidence of vomiting has decreased. However, even the latest agents have failed to eradicate this troublesome symptom encountered in the peri-operative period.
Nausea and vomiting has many causes including drugs, motion sickness, fear, pregnancy, vestibular disease and migraine. In previous decades anaesthesia was almost synonymous with vomiting, but with the advent of new anaesthetic agents and more aggressive treatment the incidence of vomiting has decreased. However, even the latest agents have failed to eradicate this troublesome symptom encountered in the peri-operative period.
Physiology
The vomiting centre (VC) coordinates vomiting. It has no discrete anatomical site but may be considered as a collection of effector neurones situated in the medulla. This collection projects to the vagus and phrenic nerves and also to the spinal motor neurones supplying the abdominal muscles, which when acting together bring about the vomiting reflex.
The VC has important input from the chemoreceptor trigger zone (CTZ), which lies in the area postrema on the floor of the fourth ventricle but is functionally outside the blood–brain barrier. The CTZ is rich in dopamine (D2) receptors and also serotonin (5-HT) receptors. Acetylcholine (ACh) is important in neural transmission from the vestibular apparatus. Other input is summarised in Figure 19.1.
Figure 19.1 Summary of the various neural inputs that result in vomiting.
The treatment of nausea and vomiting is aimed at reducing the afferent supply to the VC. While the administration of antiemetics forms a vital part of treatment, attention should also be given to minimising the administration of opioids by the use of non-steroidal anti-inflammatory drugs and avoiding unnecessary anticholinesterase administration. When propofol is used to maintain anaesthesia for minor surgery, where the use of opioids is limited, it may reduce the incidence of post-operative nausea and vomiting (PONV).
The following types of agents have been used:
Dopamine antagonists
Anticholinergics
Antihistamines
5-HT3 antagonists
Neurokinin (NK) antagonists
Miscellaneous.
Dopamine Antagonists
Phenothiazines
Phenothiazines are the main group of anti-psychotic drugs (neuroleptics) and have only a limited role in the treatment of vomiting. They are divided into three groups on the basis of structure, which confers typical pharmacological characteristics (see Table 19.1).
Chlorpromazine
Chlorpromazine’s proprietary name ‘Largactil’ hints at the widespread effects of this drug.
Uses
Chlorpromazine is used in schizophrenia for its sedative properties and to correct altered thought. Its effects on central neural pathways are complicated but are thought to involve isolating the reticular activating system from its afferent connections. This results in sedation, disregard of external stimuli and a reduction in motor activity (neurolepsy). It is sometimes used to control vomiting or pain in terminal care where other agents have been unsuccessful. It has also been shown to be effective in preventing PONV. It is occasionally used to treat hiccup.
Mechanism of Action
Chlorpromazine antagonises the following receptor types: dopaminergic (D2), muscarinic, noradrenergic (α1 and α2), histaminergic (H1) and serotonergic (5-HT). It also has membrane stabilising properties and prevents noradrenaline uptake into sympathetic nerves (uptake 1).
Effects
Central nervous system – extrapyramidal effects are due to central dopamine antagonism. The neuroleptic malignant syndrome occurs rarely. It has variable effects on hypothalamic function, reducing the secretion of growth hormone while increasing the release of prolactin (dopamine functions as prolactin release inhibitory factor). Temperature regulation is altered and may result in hypothermia.
Cardiovascular – it antagonises α-adrenoceptors resulting in peripheral vasodilation, hypotension and increased heat loss.
Anticholinergic – it has moderate anticholinergic effects.
Gut – appetite is increased and patients tend to gain weight (exacerbated by inactivity). While it has been shown to be an adequate antiemetic, its other effects have limited this role.
Miscellaneous – contact sensitisation. Direct contact should be avoided unless actually taking chlorpromazine. Cholestatic jaundice, agranulocytosis, leucopenia, leucocytosis and haemolytic anaemia are all recognised.
Kinetics
Absorption from the gut is good but, due to a large hepatic first-pass metabolism (limiting its oral bioavailability to about 30%), it is often given parenterally. The large number of hepatic metabolites is excreted in the urine or bile, while a variable but small fraction is excreted unchanged in the urine.
Prochlorperazine
Uses
Prochlorperazine is effective in the prevention and treatment of PONV and vertigo, as well as in schizophrenia and other psychoses.
Effects
Central nervous system – extrapyramidal effects are seen more commonly in this class of phenothiazine (Table 19.2). Acute dystonias and akathisia seem to be the most commonly encountered effects. Children and young adults are the most affected groups. When used peri-operatively it produces only mild sedation and may prolong the recovery time but the effects are not marked.
Group specific – in common with other phenothiazines, prochlorperazine may cause cholestatic jaundice, haematological abnormalities, skin sensitisation, hyperprolactinaemia and rarely the neuroleptic malignant syndrome.
| Sedation | Anticholinergic effects | Extrapyramidal effects | |
|---|---|---|---|
| Chlorpromazine | +++ | ++ | ++ |
| Droperidol | + | 0 | ++ |
| Metoclopramide | + | 0 | ++ |
| Domperidone | + | 0 | 0 |
| Prochlorperazine | + | + | +++ |
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