Palliative Care: Nausea and Vomiting Questions Flashcards
A 75 year old man with lung cancer, presenting with early morning headache and nausea, has had a CT brain, which confirms brain metastases with evidence of mild raised ICP. Turning his head exacerbates the nausea.
a) Which anti-emetic would you consider first line?
a) Cyclizine.
First consider which anti-emetic is first line for raised ICP.
A 75 year old man with lung cancer, presenting with early morning headache and nausea, has had a CT brain, which confirms brain metastases with evidence of mild raised ICP. Turning his head exacerbates the nausea.
b) Which receptors relevant to nausea and vomiting does this drug act at?
b) H1 receptors (+ muscarinic receptors) at the vomiting centre
A 75 year old man with lung cancer, presenting with early morning headache and nausea, has had a CT brain, which confirms brain metastases with evidence of mild raised ICP. Turning his head exacerbates the nausea.
c) Which potential side-effects would you be particularly vigilant about in this patient?
c) Drowsiness = falls risk + anti-muscarinic side-effects = confusion/urinary retention/constipation (factors in delirium/falls)
A 75 year old man with lung cancer, presenting with early morning headache and nausea, has had a CT brain, which confirms brain metastases with evidence of mild raised ICP. Turning his head exacerbates the nausea.
d) What other drug might you consider starting?
d) Dexamethasone (increased ICP)
A 45 year old lady with newly diagnosed resectable cholangiocarcinoma and T1DM complicated by stage 3 CKD and peripheral neuropathy, describes a 3 month history of nausea arising when she tries to eat her meals, early satiety and occasional vomiting of undigested food stuffs during or after meals.
a) Which anti-emetic would you consider first line?
a) Metoclopramide.
Look at the stem. She has a cholangiocarcinoma - think of the mass effect of obstructing the duodenum or causing an ileus. She has T1DM which can result in autonomic neuropathy and a resultant gastroparesis. We can additionally see that this is a proximal GI tract nausea as the food is undigested with early satiety.
With this in mind, consider metoclopramide’s MOA. It is gastroprokinetic (which is what we need here) - mediated by dopamine (D2) receptor antagonism and 5HT4 receptor agonist activity. Moreover, the anti-emetic effect is primarily mediated by antagonising the D2 receptor activity at the chemoreceptor trigger zone (CTZ) in the CNS.
A 45 year old lady with newly diagnosed resectable cholangiocarcinoma and T1DM complicated by stage 3 CKD and peripheral neuropathy, describes a 3 month history of nausea arising when she tries to eat her meals, early satiety and occasional vomiting of undigested food stuffs during or after meals.
b) What dose and how often?
b) 10 mg TDS before food
A 45 year old lady with newly diagnosed resectable cholangiocarcinoma and T1DM complicated by stage 3 CKD and peripheral neuropathy, describes a 3 month history of nausea arising when she tries to eat her meals, early satiety and occasional vomiting of undigested food stuffs during or after meals.
c) What side effects would she experience?
Extrapyramidal side-effects (D2 blocking):
- Akathisia (restlessness)
- Tardive dyskinesia
- Acute dystonia
- Parkinsonism
- Galactorrhoea (hyperprolactinaemia)
A 70 year old man with bowel cancer metastatic to the liver describes nausea that is exacerbated by the sight or smell of food. His LFTs are mildly deranged and his corrected calcium is 2.9 mmol/L (2.6 mmol/L upper range of normal).
a) What is the most likely mechanism causing his nausea?
a) Chemical nausea.
Constant not intermittent.
Could be increased [Ca2+] or his liver itself not breaking down toxins i.e. getting higher levels of drugs (or both).
A 70 year old man with bowel cancer metastatic to the liver describes nausea that is exacerbated by the sight or smell of food. His LFTs are mildly deranged and his corrected calcium is 2.9 mmol/L (2.6 mmol/L upper range of normal).
b) What drug would you consider first-line and why?
b) Haloperidol
Chemical nausea therefore we need to target the CTZ at the medulla oblongata. We require a potent dopamine (D2) receptor antagonist to achieve this. Haloperidol is more potent than metoclopramide.
A 70 year old man with bowel cancer metastatic to the liver describes nausea that is exacerbated by the sight or smell of food. His LFTs are mildly deranged and his corrected calcium is 2.9 mmol/L (2.6 mmol/L upper range of normal).
c) What other interventions would you consider?
c) We need to treated his hypercalcaemia.
Give IV 0.9% NaCl 1 L
+ zolendronic acid.
A 58 year old lady with metastatic ovarian cancer has widespread peritoneal and mesenteric disease causing sub-acute mechanical bowel obstruction at the ileum and transverse colon. She is on levomepromazine 25 mg, ranitidine 200 mg and hyoscine butylbromide 90 mg via CSCI/24 hours. She vomits every 48 hours but has ongoing persistent nausea.
a) What class of anti-emetic would you consider adding?
b) Why?
a) Ondansetron.
b) We need to think about what the mechanism of the nausea/vomiting. She has sub-acute bowel obstruction due to her metastatic cancer. Proximal to this, food is continuing to digest/begins fermenting and the intestine is absorbing this. These endothelial cells are then damaged and subsequently release 5HT3 (the same process happens in response to chemotherapeutic agents where ondansetron is required). Ondansetron itself is a highly specific and selective serotonin 5-HT3 receptor antagonist, with low affinity for dopamine receptors. The 5-HT3 receptors are present both peripherally on vagal nerve terminals and centrally in the CTZ in the medulla. Serotonin is released by the enterochromaffin cells of the small intestine in response to chemotherapeutic agents and may stimulate vagal afferents (via 5-HT3 receptors) to initiate the vomiting reflex.
A 58 year old lady with metastatic ovarian cancer has widespread peritoneal and mesenteric disease causing sub-acute mechanical bowel obstruction at the ileum and transverse colon. She is on levomepromazine 25 mg, ranitidine 200 mg and hyoscine butylbromide 90 mg via CSCI/24 hours. She vomits every 48 hours but has ongoing persistent nausea.
c) As an aside, outline briefly the MOA of levomepromazine, ranitidine, and hyoscine butylbromide.
c) Levomepromazine - D2 receptor antagonist/ACh receptor antagonist/H1-receptor antagonist. Sedative effects hence not used often.
Ranitidine - H2-receptor antagonist.
Hyoscine butylbromide - buscopan - anti-spasmodic at smooth muscle
A 36 year old man on second-line chemotherapy for metastatic bowel cancer is due a re-staging CT. He explains that on the last two occasions he underwent a CT he experienced nausea and vomiting. He describes feeling oberwhelming distress immediately after the first CT scan he ever had, when he was given the news of his diagnosis of cancer in the X-ray department. He asks if you could prescribe a medication to prevent this the next time.
a) What might be the mechanism of his nausea and vomiting?
a) Emotional.
A 36 year old man on second-line chemotherapy for metastatic bowel cancer is due a re-staging CT. He explains that on the last two occasions he underwent a CT he experienced nausea and vomiting. He describes feeling oberwhelming distress immediately after the first CT scan he ever had, when he was given the news of his diagnosis of cancer in the X-ray department. He asks if you could prescribe a medication to prevent this the next time.
b) What class of medications will you prescribe?
b) A benzodiazepine.
Lorazepam.
GABA at cerebral cortex - acts at higher centres.
