Nausea And Vomiting

Question 1

Common causes for nausea in palliative care

Answer 1

1. Constipation
2. Delayed gastric emptying and gastric distention - Gastroparesis associated with medication for example opioids
   - Gastric Outlet obstruction by tumor.
3. Severe pain
4. Ileus
5. Medications (opioids, ssri, nsaids, digoxin toxicity)
6. Malignant bowel obstruction
7. Metabolic and endocrine (hypercalcemia, hyponatremia, adrenal insufficiency)
8. Intracranial disease
9. Chemotherapy or radiation
10. Esophagitis
11. Poor oral intake
12. Infection
13. Vestibular apparatus stimuli

Question 2

Pathophysiology of emesis centers

Answer 2

Input from these stimuli
-Chemo receptor trigger zone (CTZ) is located in the floor of the 4th ventricle in the brain stem, exposed to both blood and csf.
-upper gi tract and pharynx :
Chemo R in intestines and liver, mechano R in viscera
-vestibular apparatus (histamine R H1, Ach m)
-brain cortex (GABA R, cannabinoid C1R)
All have pathways to the vomiting center (VC) in the center of the brain. (Ach m, H1, 5HT2)
VC has autonomic efferent pathways to upper GI, diaphragm and abdominal muscles.
Other brain center are also activated and creates tachycardia, sweating, pallor and salivation.

Question 3

Tell me more about CTZ? Chemoreceptor trigger zone

Answer 3

Many of the nausea causes triggers this Zone. Drugs such as opiates and ssris, metabolic causes, and infections tend to trigger nausea and emesis through this area. Dopeman is the dominant neurotransmitter here. Also serotonin (5HT3)
Substance p (neurokinin 1 r).

Question 4

What does Metoclopramide do? CI? SE?

Answer 4

Anti dopaminergic + pro kinetic (limited to the stomach, mediated through 5HT4 R, that stimulate acetylcholine release and promotes motility).
At very high doses acts as 5HT3 antagonist
CI - complete bowel obstruction, Parkinson
SE - eps (uncommon)
Duration of action 2-8 hours
Dosing - 10-20 mg po /sc TID - QID / q6hr.
In refractory cases, can use continuous sc infusion : 60-120 mg / day
Don’t combine with anticholinergic as will cancel out each other

Question 5

Domperidone..?

Answer 5

Similar profile to metoclopramide
Don’t cross BBB as well so less eps.
Only po.
Dosing 10 mg po tid (max 30mg /day)

Question 6

Quick pick for nausea

Answer 6

Opioid induced - metoclopramide, domperidone or Haldol
MBO - Haldol, dimenhydrinate or 5HT3 antagonist 2nd line
Chemo / radiotherapy induced - 5HT3 first line, cannabinoids 2nd line, steroids, metoclopramide
Anticipatory /anxiety related - benzodiazepine, hypnotherapy
Motion sickness - dimenhydrinate, prochlorperazine or hyoscine hydrobromide

Question 7

Haldol as antinausea

Answer 7

Potent central D2 antagonist, significantly more than metoclopramide. = more risk for EPS.
Low-moderate sedation.
Long duration of action, up to 24h. Plasma t1/2 is 13-35 hr. Thus usually given q8hr.
Usually start low 0.5 mg and monitor for eps (do you feel restless?)

Question 8

Methotrimeprazine as antinausea

Answer 8

Broad anti emetic,
Potent 5HT2 and D2 antagonist, to a lesser degree - H1 and ACHm R antagonist.
Sedating
2nd line option for nausea.
Very small dose as 2mg bid /tid up to 5-12.5 mg each dose.

Question 9

Other phenothiazines as antinausea

Answer 9

Chloropromazine (largactil) :
Modest antiemetic, causes SE and hypotension
Prochlorperazine strong antiemetic however eps more common. 5-10mg po/pr QID - q4hr usually safe.

Question 10

Atypical antipsychotic

Answer 10

Olanzapine
Broad mechanism of action: potent D1, D2, D4 R, 5HT2a, 5HT2c R antagonist. To a lesser degree binds to H1, A1 adrenergic and ACHm R.
Less EPS than other antidopaminergic agents.
Not much evidence for use in palliative settings.
Worth a trial if patient is also delirious.
2.5-10 mg po QHS /BID.
available as oral disintegration, absorbs in distal bowel so no role in small MBO.

Question 11

5HT3 antagonists

Answer 11

Expensive and only relevant in selective cases.
Considered a third line in palliative care, trial for 3 days and ineffective, discontinued.
Works on reducing vagal nerve activity.

Ondansetron: drug of choice for patients with chemo or radiotherapy induced nausea. Doze is 4-8 mg oral SC or IV TID.
May cause constipation.

Granisetron same as above, can be given OD/bid
1-2 mg po/sc/iv.
T1/2 4-9 hr

Question 12

Antihistamine

Answer 12

Useful for motion related nausea.
May also be useful in MBO when patient cannot receive prokinetic agents and cannot tolerate anti-doping agents.
May be useful as second line for nausea related to brain involvement.
Can be sedating.
Dimenhydrinate 25 mg - 50 mg po/pr / sc/ iv. Tid to QID.
Travamin Israel
Gravol Canada

Question 13

Anticholinergic agents

Answer 13

Hyoscine hydrobromide (scopolamine)
Second-line drug for motion induced nausea. Useful to reduce airway secretion and to a lesser degree secretions from bowel obstructions. 
Available and parenteral formulation for SC 0.2-0.6mg q2hr prn or ATC,  or transdermally 1.5 mg TD q3days. 

Hyoscine butylbromide (buscopan) 
Does not cross blood-brain barrier therefore does not cause drowsiness but also does not have Central antiemetic effect. 
Not use much for the management of nausea.
 Use more frequently for managing colic related to bowel or to genitourinary obstruction.

Question 14

Refractory nausea

Answer 14

1. reasse possible causes and agents tried.
2. considered metoclopramide by continuous subcutaneous infusion a dose of 60 - 120 mg a day or broad action antiemetic like nozinan.
3. corticosteroids- exact mechanism of action is unclear possibly on the brain cortex. Dexamethasone 4 to 8 mg OD to TID can be tried.