Nausea Flashcards by Caitlin L

Causes of nausea at EOL

GI Factors:

Pharyngeal Irritation (Oral/esophageal candidiasis, tenacious sputum/persistent cough)
Gastric irritation (PUD, gastritis)
Gastric stasis (Opioids or anticholinergics, hepatomegaly or GOO)
Stretching or distortion of the GI tract (Constipation, intestinal obstruction, mesenteric mets)
Infections of the GI tract (fungal, bacterial, parasitic infections - particularly in HIV/AIDS)

Meds:

Opioids, particularly intro or increase
Cytotoxic drugs
SSRIs
Antivirals or Antibiotics

Metabolic

Hypercalcemia
Renal failure
Liver failure
DM
Cytokine or other tumour factors

Cranial

Raised ICP secondary to brain mets or leptomeningeal involvement, post-rads
CNS infections (AIDS)

Psychosomatic
- Anxiety, pain, anticipator nausea

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Pathophysiology of emesis - Chemoreceptor Trigger Zone

Chemoreceptor Trigger Zone (area postrema in fourth ventricle)

 - No blood brain barrier
 - Bathed in CSF with chemoreceptors (D2, serotonin, and cannabinoid) responsive to drugs and electrolytes
 - Relays neurotransmitters to Vomiting Centre and vomiting reflex

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Pathophysiology of Emesis - Vomiting Centre

Vomiting Centre is a diffuse network in the medulla oblongata of the mid brainstem

  - Nausea without vomiting may be due to stimulation of the VC without enough amplification to trigger the vomiting cascade
   - H1, acetylcholine, serotonin receptors
   - Input from the CTZ, vestibular apparatus and cerebellum, higher cortex, gut chemoreceptors and mechanoreceptors, mechanoreceptors in viscera/serosa (head and neck, thorax, abdomen, pelvis)
   - Stimulation causes parasympathetic and sympathetic output as well as neurotransmitter cascade to induce vomiting

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Inputs to Vomiting Centre

CTZ (area postrema in fourth ventricle)
- D2, serotonin 5-HT3, opioid receptors, acetylcholine receptors, substance P reeptors

Vestibular system (via CN 8 - vestibulocochlear), motion sickness
- muscarinic and H1 receptors

CN X (vagal nerve)
- pharyngeal irritation (gag reflex)

Vagal and enteric nervous system (chemoreceptors, mechanoreceptors in gut, mechanoreceptors from viscera/serosa), D2 and Serotonin

CNS (psychiatric disorders, stress), H1 receptor

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Approach to Nausea/Vomiting

Identify likely cause(s) and evaluate for dehydration, potential for opioid neurotoxicity
Identify pathway by which each case triggers vomiting reflex
Identify neurotransmitter pathway
Choose most potent antagonist to the receptor identified (dictated by binding affinity)
Choose route (often not oral as patients may not be able to tolerate)
Titrate carefully
Give regularly
If symptoms persist - review likely cause and consider overlooked causes or other contributing causes
Consider combining antiemetics, but be mindful of interactions (antihistamines and anticholinergics may counteract prokinetics!)

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Rx for Opioid nausea, neurotransmitter and site

CTZ
D2 receptor
Haldol 1.5 - 5mg q8-12h, PO or SC (first line)
Levomepromazine 5 - 12.5mg q daily, PO or SC
Prochlorperazine 5-10mg (PO, SC, IV) BID-QID

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Rx for Gastric stasis, Ileus, neurotransmitter and site

Gastroinstestinal site
Serotonin (to a lesser extent, dopamine, histamine, Ach)
Prokinetics preferred
Domperidone 10-20mg PO q4-8H AC meals
Metaclopramide - 10-20 mg PO/SC/IV TID AC meals

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Rx for Gastric Obstruction, neurotransmitter and site

Gastroinstestinal site
Serotonin (to a lesser extent, dopamine, histamine, Ach)
Phenothiazines, antihistamines, anticholinergics
Levomepromazine 5-12.5mg/24hr PO/SC
Cyclizine 25-50mg PO/SC/PR q8h
Scopolamine 20mg PO/SC q6h (especially if colicky)
Dex 8mg qAM to try to relieve obstruction (trial for 4-5 days)

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Rx for Chemotherapy nausea, neurotransmitter and site

**Check guidelines from ASCO for this

CTZ (area postrema in fourth ventricle) and gastrointestinal site
CTZ = dopamine, GI site = serotonin (to a lesser extent for both, Ach and histamine)
5-HT3 antagonists, NK1 antagonist, prokinetics
Ondansetron 8mg PO/SC (consider addition of Dex to enhance efficacy)
Aprepitant 125mg PO 1hr prior to chemo, then 80mg OD for the next two days
Metoclopramide 10-20mg PO/SC q4h

Also consider haldol, and olanzapine 5-10mg q daily on days before and during chemo has been found to be effective, though evidence may be poor.

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Rx for raised ICP nausea, neurotransmitter and site

Cerebral Cortex
GABA, Histamine

-Use Phenothiazines (prochlorperazine 5-10mg/12.5-25m IM q8H) along with Dex for decreasing ICP

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Maxeran for Nausea (indications, dose, side effects, notes)

Metoclopramide 10-20mg PO/SC/IV q4H

CTZ and GI tract, D2. Note that metoclopramide potentiates 5-HT3 receptors (may be used with ondansetron, but watch QT) and can act on 5-HT3 at higher doses. Central antiemetic effect plus prokinetic effect and decreased pylorus activity - food passes through more quickly.

Indications: Gastric stasis, ileus (avoid in complete obstruction), may use for Chemotherapy

Do not combine with anticholinergics (scopolamine, hyoscine, diphenhydramine) due to counteracting effects. Note that olanzapine, levomepromazine also have anticholingeric effects and increase risk of EPS.

Side effects: EPS, restlessness, drowsiness, colic in GI obstruction. Risk of tardive dyskinesia, especially if used longer than 12 weeks, at higher doses, or in patients under 20 years old. Risk increased with combination with antipsychotics!

Prolonged half life in renal failure, long QTc. Caution in Parkison’s (may worsen symptoms as a dopamine antagonist)

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EPS with anti-nauseants - symptoms, pathophys, agents

Symptoms: Parkinsonism, dystonia, tardive dyskinesia, akathisia

Seen with Maxeran and prochlorperazine overdose (usually but not always reversible)

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Levomepromazine for nausea (indications, dose, side effects, notes)

5-12mg PO/SC over 24 hrs (BID or continuous SC infusion)

Receptors: D2, 5HT2, H1, acting on VC

Indications: Intestinal obstruction, peritoneal irritation, vestibular, raised ICP, unknown causes

Side effects: Long QTc, sedating, orthostasis, anticholinergic effects (esp in elderly) - confusion, hallucinations, EPS

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Non-pharm measures for nausea

Citrus
Ginger
Peppermint
Cold, lightly carbonated beverages
Hydration
Decrease odours

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Glucocorticoids for nausea (indications, dose, side effects, notes)

Exact mechanism unknown, likely glucocorticoid receptors in central nucleus.

Dexamethasone 4-8 mg PO qAm (higher doses if related to increased ICP)

Side effects: Hyperglycemia, Cushing syndrome, weight gain, PUD, infection, aseptic necrosis (femoral/humerol heads), impaired wound healing, steroid psychosis, adrenal suppression,

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Pearls:

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Antiemetics are better at vomiting control than nausea, but a higher dose may control nausesa better
Initially, use a single drug to maximum tolerated dose
Broader spectrum drugs (methotrimeprazine, olanzapine) may be as effective as multiple simultaneous antiemetics
Oral administration is preferred, but consider parenteral if the patient has vomiting, malabsorption, or stasis. After 3 days, consider converting to PO administration except in cases of mechanical obstruction

Combinations to avoid

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Prokinetics (maxeran) and anticholinergics (dimenhydrinate, scopolamine) as combination is illogical

Maxeran with antipsychotics (increased risk of EPS)

Cannabis for nausea - evidence

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No controlled clinical efficacy studies

Nabilone

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Antiemetic alternative

Nabilone 0.25 - 2mg PO BID (start low)

Acts on cannabinoid receptors (CB1) in CNS

Side effects: Drowsiness, dizziness, vertigo, euophoria, ataxia, xerosteomia

Approach to opioid nausea

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Antiemetics may be helpful, but no clear evidence for a preferred antiemetic choice
Switching opioids or route may help.
Note that most patients develop tolerance to the emetic effect of opioids after 5-7 days, and so anti-nauseants after that point can be PRN (or a half hour prior to meals if connected with eating)

Epidemiology of Nausea and Vomiting (cancer)

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Occurs in 50-70% of patients with advanced cancer

Epidemiology of Nausea and Vomiting (AIDS)

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43 - 49% of patients with AIDS

Epidemiology of Nausea and Vomiting (ESRD)

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30 - 43% ESRD

Epidemiology of Nausea and Vomiting (Advanced cardiac disease)

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17 - 48% Advanced Cardiac Disease

Epidemiology of Nausea and Vomiting (Multiple Sclerosis)

26% in MS

Antihistamines for vomiting - examples, receptors, site of effect, and side effects

- Dimenhydrinate 50-100mg PO/subcut q6h PRN, cyclizine 25-50mg PO/SC/PR q8H - H1 - Works at CTZ, GIT, CNS, VC, Vestibular nuclei - Useful for motion sickness - Side effects: Sedation, constipation (often avoided for these reasons)

Anticholinergics for vomiting - examples, receptors, site of effect, and side effects

- Scopoloamine 20mg PO/SC q6h - Targets ACh - Works at VC, GIT - Useful for intestinal obstruction, peritoneal irritation, raised ICP, excess secretions - Side effects: Dry mouth, sedation, ileus, urinary retention, blurred vision, occasionally agitation - Useful if NV coexist with colic, illogical to give with prokinetics

Phenothiazines for Nausea/vomiting - examples, receptors, site of effect, and side effects

- Prochlorperazine 5-10mg PO, 12.5-25mg IM q4-6H regular, q1H PRN - Methotrimeprazine (Nozinan) 6.25-12.5mg PO/SC q6H reg, PRN - Targets D2, H1, 5HT3, ACh (Prochlorperazine only for ACh) - Works at CTZ, GIT, VC, CNS (but NOT vestibular nuclei) - Useful for intestinal obstruction, peritoneal irritation, nausea of unknown etiology, vestibular causes, raised ICP - Side effects include drowsiness, orthostatic hypotension - Prochlorperazine can cause EPS (less likely with Nozinan)

Serotonin antagonists for nausea/vomiting - examples, receptors, site of effect, and side effects

- Ondansetron 8mg PO/SC/IV q8H - Targets 5HT3 - Works at GIT, CTZ - Useful for chemotherapy, abdominal radiotherapy, post op NV - Side effects: Constipation - Note - expensive

Butyrophenones for nausea/vomiting - examples, receptors, site of effect, and side effects

- Haldol 1.5-5.0mg/day PO or SC in two divided doses, plus hourly PRN - Targets D2 - Works at CTZ - Useful for opioid-related nausea, chemical or metabolic nausea - Side effects: EPS (at higher doses) QTc, somnolence. Side effects unusual at lower doses - Caution with liver impairment

Cannabinoids for nausea/vomiting - examples, receptors, site of effect, and side effects

- Nabilone 1-2mg PO BID - CB1 receptor - Works at CNS, GIT (decreases intestinal motility) - Side effects: Euphoria, dysphoria, anxiety, mania, tachycardia, dry mouth, appetite stimulation, later drowsiness - Use with caution, not first line

Prokinetics for Nausea/vomiting - examples, receptors, site of effect, and side effects

- Maxeran 10mg PO/SC/IV q4-8H - Domperidone 10-20mg PO/q4-8H – cannot be given parentally - Targets D2 (Maxeran targets 5HT4 at higher doses) - Works at GIT, CTZ - Useful for gastric stasis or ileus - Side effects: Colic if obstruction, long QTc, EPS (maxeran, note Domperidone does not cause BBB

Anxiolytics for nausea/vomiting - examples, receptors, site of effect, and side effects

- Lorazepam 1mg PO/SL - Works at CNS - Useful for anticipatory nausea/vomiting - Side effects: Drowsiness, lethargy, confusion – caution when combining with opioids

Dexamethasone for nausea/vomiting - examples, receptors, site of effect, and side effects

- Dexamethasone 4mg PO qDaily - Mechanism of action not well understood, works well with Aprepitant or Ondansetron with highly emetogenic chemo - Side effects: Confusion, euphoria, insomnia, psychosis, fluid retention, gastric irritation, hyperglycemia, osteoporosis, osteonecrosis (long term)

NK1 antagonists for nausea/vomiting, examples, receptors, site of effect, and side effects

- Aprepitant 125mg PO prior to chemo, 80mg per day there after for two days - NK1, wide spread site of activity - Used for late onset chemotherapy NV - Side effects: hiccups, asthenia, fatigue, anxiety, somnolence

Nausea Flashcards

(35 cards)