Nausea and Vomiting Flashcards
Causes of nausea and vomiting
-
Pharyngeal irrtatation
- oral/esophageal candidiasis
- tenacious sputum
-
Gastric irritation
- PUD
- Gastritis
-
Gastric stasis
- OPioids
- ACH
- hepatomegaly
- gastric outlet obstruction
- autonomic dysfunction (anorexia-cachexia)
-
Stretching of GI tract
- constipation
- MBO
- mesenteric metastases
-
Infection
- bacterial, viral, fungal infxn in AIDS/HIV
-
Medications
- opioids (30% of patients)
- cytotoxic drugs
- SSRI
- antivirals
- antibiotics
- any drug
-
Metabolic causes
- hyerpcalcemia
- renal failure
- liver failure
- DM
-
Raised intracranial pressure
- primary tumour/mets
- cerebral infections (HIV AIDS)
-
Movement induced
- vestibular disorders
- traction on tumor in mesentery/viscera
-
Psychosomatic causes
- anxiety
- pain
- Anticipatory nausea
-
Tumour induced
- Autonomic dysfunction
- cytokines
Assessment of nausea and vomiting (History)
- Medications
- full review of systems
- past medical hx (PUD, gastritis)
- meaning of nausea and vomiting
- Triggers or alleviating factors
- frequency (can lead to dehydration, OIN)
- Nature of vomitus (feculent, hematemesis)
- Vomiting without nausea = proximal bowel obstruction or raised ICP
- Neuro or cognitive changes
- numerical analog scale rating
Physical exam for Nausea and vomiting
- dehydration / volume status
- abnormalities of the GI tract
- constipation
- hepatomegaly
- obstruction
- signs of raised ICP or CNS infection
Laboratory investigations for nausea and vomiting
- Cr, urea
- hypercalcemia
- Hyponatremia
- Hypomagnesemia
- liver failure
- Blood glucose
- Abdominal Xray
Nausea defintion
- Subjective sensation
- Unpleasant expression of autonomic stimulation
- pallor, diaphoresis
- salivation
- signals imminent vomiting
Chemoreceptor Trigger Zone
- functional entity in area postrema on floor of fourth ventricle
- area postrema : medulla oblongata
- circumventricular organ with permeable capillaries and sensory neurons that enable dual role to detect circulating chemical messengers in blood and transduce them into neural signals
- transmits to VC
- Outside BBB
- bathed by systemic circulation
- D2 receptors in area postrema stimulated by high concentrations of emetogenic substances
- medications or metabolic disturbances
- 5Ht3
- cannabinoids
Receptor pathways and neurotransmitters chart
Vomiting centre
- Not a specific anatomical entity
- diffuse network in medulla oblongata that gathers input and acts as a central pattern generator for the vomiting reflex
- H1, AchM, 5HT2
- receives input from
- CRTZ (D2, 5HT3)
- Vagal and sympathetic afferents (D2, 5HT4)
- liver, gut, pharynx
- vestibular nuclei (H1, M)
- Cortex (H1)
- Stimulation causes parasympathetic and sympathetic output as well as neurotransmitter cascade to induce vomiting
- Nausea without vomiting may be stimulation of VC without sufficient amplification to trigger vx.
Antiemetic medications and side effects : Vomiting Centre
-
Antihistamine/Anticholingeric
- cyclizine, dimenhydrinate, diphenhydramine (drowsy, dry mouth, constipation)
-
Anticholingergic
- Hyoscine hydrobromide (scopolamine) : EPS, dry mouth, constipation, sedation, hypotension
-
Serotonin antagonists
- ondanstron, granisetron, tropistetron : expensive, HA, constipation
- metoclopramide high doses : drowsiness, EPS
Antiemetic medications and side effects: CRTZ
-
Dopamine antagonists (D2)
- haldol : EPS
- butyrophenones : EPS
- phenothiazines (methotrimpeprazine, prochlorperazine) : EPS, sedation
- Prokinetics metoclopramide : EPS
- Domperidone (Does not cross BBB) : less EPS
-
Serotonin antagonists
- ondansetron
- metoclopramide at high doses
-
Cannabinoids
- Dronabinol
- Nabilone : euphoria, dysphoria, anxiety, mania, tachycardia, dry mouth, appetite
Antiemetic medications and side effects: Gut receptors and vagus nerve
-
Dopamine antagonists
- butyrophenones HALDOL : eps
- Phenothiazines (prochlorperazine, methotrimeprazine) : EPS, sedation
- Prokinetics (domperidone, metoclopramide) : EPS
-
Serotonin antagonists
- ondanstron
- metoclopramide at high doses
Antiemetic medications and side effects: vestibular nuclei
-
Anticholingeric
- scopolamine (hyoscine hydrobromide) : sedation, dry mouth, constipation, delirium, IOP, urinary retention)
-
Antihistamines / anticholinergics
- Cyclizine, diphenhydramine, dimenhydrinate
- Phenothiazine (methotrimep, prochlorperazine)
Antiemetic medications and side effects: Cortex
- Antihistamines/ anticholingerics
- Anxiolytics
- benzos
- Cannabinoids
- nabilone, dronabinol
- Corticosteroids
- dex
Dosages and routes of administration of anti-emetics
-
Metoclopramide
- 30-60 mg / day up to 120 mg/day
- q4-6 h ATC and hourly if needed
- oral, SC, IV
-
Haldol
- 0.5-5 mg/day div bid
- QHS, BID, q1h prn
- oral, sc, IV
-
Prochlorperazine
- 5-10 mg po, 10-20 mg rectally
- q4h ATC and q1h prn
- oral, rectal
-
Domperidone
- 10 mg
- q4h -q6h ATC and q1h prn
- oral
-
Cyclizine
- 25-50 mg
- q8h
- oral, sc, rectal
Non pharmacological approaches to nausea and vomiting
- avoid sight or smell of triggering food / odours
- small frequent bland meals
- good oral hygiene
- fresh air, calm environment
- distractions
- sitting upright after a meal
- acupuncture
- acupressure (pericardium P6 or Neiguan acupoint on anterior surface of forearm 3cm proximal to wrist crease)
- Psychological techniques not studied
Hypercalcemia of malignancy
- 10-40% cancer patients, myeloma, breast, lung, renal cancers
- Bone mets 20% of hypercalcemia
- PTH protein secretion 80% hypercalcemia
- nausea, vomiting, constipation, weakness, polydipsia, polyuria, somnolence, confusion, agitation, anorexia
Corrected Serum Calcium level (mmol/L)
Corrected serum calcium level (mmol/L) =
serum calcium (mmol/L) + [(40-albumin g/L) x 0.02]
Normal < 2.65
Ionized calcium best in myeloma (paraproteins have calcium binding effects)
Hypercalcemia of malignancy treatment
- Rehydration + bisphosphonate
- worsens renal failure
- symptomatic hypocalcemia rare
- Calcitonin temporary relief 100u sc tid for 1-2 days
Bisphosphonates
- Clodronate
- 1500 mg, 900 mg if Cr > 150 mmol/L
- sc, iv over 4 hours
- works within 2-3 days
- duration 2 weeks
- Pamidronate
- 60-90 mg
- IV over 4 hours
- works within 3-7 days
- duration 3-4 weeks
- Zoledronic acid
- 4 mg
- IV over 15 minutes
- works withint 3-7 days
- 4-6 weeks duration
Tips for management of nausea and vomiting : CBM
- nausea is very distressing
- multifactorial, aim to treat receptor
- D2 antagonists: metoclopramide, haldol, prochloperazine
- Antihistamine : cyclizine, limiting side effects
- SC routes
- interprofessional team
- always check for constipation
Other medications options
- atypical antipsychotics (olanzapine)
- benzos: anticipatory nausea,
- Octreotide:
- Somatostatin analogue
- inhibits endocrine and exocrine gut secretions, reabsorption of electrolytes in gut
- restore GI transit
- Propofol
- antiemetic, CRTZ
- Opioids: not useful
- Mirtazapine :
- 5Ht3 antagonism
- anecdotal reports
Vomiting definition
- objective patient experience involving forcefaul elmination of the contents of the stomach by the sustained action of abdominal muscles and opening of gastric cardia
Diagram of CRTZ, VC and afferent inputs
Afferent pathways to vomiting centre
- VAGUS
- splanchnic nerves
- sympathetic ganglia
- glossopharyngeal nerve
- Vagus stimulated by mechanoreceptors and chemoreceptors in GI tract and vscera
- “Higher centres”
Approach to Nausea and Vomiting Management
- Identify likely causes
- Identify pathway
- Identify neurotransmitter receptor
- Choose most potent antagonist
- Choose route of administration (SC/IV > oral)
- Titrate dose carefully
- GIVE ANTIEMETIC REGULARLY
- If symptoms persist, review likely cause
- If combining antiemetics, look at potential drug interactions. (Eg. antihistamines counteract prokinetics)
Dopamine antagonists
- Butyrophenones
- Haldol most potent at CRTZ
- Opioid induced Nausea
- Chemical/metabolic Nausea
- SE: Qtc, EPS, somnolence
- Prokinetics
- Metoclopramide
- D2, 5Ht4,
- 5Ht3 in high doses
- CRTZ, GI tract,
- gastric stasis, ileus
- SE: Qtc, EPS, Colic
- Domperidone
- D2
- CRTZ, GIT
- Does not cross BBB, few EPS
- no parenteral route (cardiac toxicity)
- Metoclopramide
Phenothiazines (Methotrimeprazine, prochlorperazine, chlorpromazine)
- D2, H1, Ach, a adrenergic
- Less potent D2 antagonists
- Moderate antihistaminergic, anticholingeric action
- CRTZ, GIT, VC, CNS, CVS
- Prochlorperazine 5-10 mg po q6-8h
- SE: Qtc, sedation, parkinsonism
- use for MBO, peritoneal irritation, nausea NYD, vestibular causes, raised ICP
- Chlorpromazine: lower seizure threshold
Antihistamines
Cyclizine
Diphenyhydramine
Diphenylhydramine
- Cyclizine H1 : less sedating
- Diphenylhydramine H1
- Promethazine H1
- Diphenylhydramine AchM
- CRTZ, GIT, CNS, VC, vestibular centre
- SE: dry mouth, blurred vision, constipation, urinary retention, sedation, EPS
- useful for vestibular disorders
Anticholinergics
- Hyoscine Hydrobromide (scopolamine)
- Hyoscine Butylbromide (buscopan)
- AchM
- VC, GIT
- Intestinal obstruction, peritoneal irritation, raised ICP, excess secretions, esophageal spasm
- Scopolamine 200-400 ug q4-8 h prn sc
- SE: dry mouth, sedaton, ileus, urinary retention, blurred vision, agitation, confusion
- Useful if nausea and colic
- Do not use with prokinetic : doesn’t make sense as anticholingerics can cause ileus
- Buscopan does not cross BBB
5HT3 antagonists
granisetron
ondansetron
tropisitron
- 5HT3
- GIT, VC, CRTZ
- chemotherapy, radiotherapy, post op NV
- SE: Headache, constipation, diarrhea, Qtc, dizziness, transient elevation of serum aminotransferases
- Effectiveness increased when combined with dexamethasone
NK1 Antagonist
Aprepitant
- NK1 receptors
- widespread in body
- Late onset chemotherapy related NV
- 125 mg po 1 hour prior to chemo, then 80 mg po od x 2 days
- SE: hiccups, asthenia, fatigue, somnolence, anxiety, anorexia, Gi upset
- PO only
Corticosteroids
- unclear mechanism
- enhance antiemetic tone in medulla
- reduce permeability of BBB to emetogenic chemicals
- depleting GABA in medulla
- reducing leu-encephalin release in brainstem
- reducing inflammationg and edema
- tumour edema
- reduces stretch on peripheral nerves
- ICP
Cannabinoids : dronabinol, nabilone
- act on peripheral CB1 receptors
- decrease intestinal motility
- may act centrally, may act on opioid receptors
- SE: psychomimetic effects,
Common syndromes that cause N/V : Chemically induced
-
Causes
- Drugs (opioids, digoxin, anticonvulsants, antibiotics, cytoxics)
- Toxins (MBO, food poisoning)
- Metabolic organ failure
- Hypercalcemic
-
Key features:
- Drug toxicity
- Constant nausea, variable vomiting
-
Pathways and receptors:
- D2 in CRTZ
- Acute CINV Chemotherapy –> 5Ht3 in vagus, VC, CRTZ
- Delayed CINV Chemotherapy –> substance P –> NK1 in brain
-
Treatment:
- stop drug
- treat underlying causes
- haldol
- 5HT3 antagonists
- NK1 for delayed emesis from chemo
Common syndromes of N/V : Gastric stasis
-
Causes:
- Ach drugs
- Opioids
- ascites, hepatomegaly
- peptic ulcer
- gastritis
-
Key features:
- epigastric pain
- fullness, early satiety
- nausea
- GERD
- hiccup
- ascites
-
Pathway and receptors:
- gastric mechanoreceptors –> vagal afferents –> VC (H1, AchM)
- Treatment
- treat underlying cause
- prokinetic agents
- reduce gastric secretions (H2 blocker, PPI, octreotide)
Common syndromes N/V: Stretch of GI tract
-
Causes
- Constipation
- MBO
- mesenteric mets
-
Key features:
- altered bowels
- nausea, vx
- colic
-
Pathways and receptors
- Gut mechanoreceptors —> vagal afferents —> VC
-
Treatment
- treat cause
- bowel management
- corticosteroids
Common syndromes N/V : Serosal stretch/irritation
-
Causes:
- liver mets, ureteric obstruction, mesenteric mets
-
Key features:
- of underlying condition, nausea, occ vx
-
Pathways and receptors:
- H1, AchM
-
Treatment
- Cyclizine
- hyoscine butylbromide if bowel paralysis acceptable
Common syndromes in N/V: Raised ICP
-
Causes:
- cerebral edema
- hemorrhage
- tumour
- LMD
- Skull mets
- Cerebral infections (AIDS)
-
Key features:
- Headaches
- papilledema
- nausea (diurnal)
-
Pathway and receptor
- Cerebral H1 meningeal mechanoreceptors –> VC (H1, ACH)
-
Treatment:
- underlying causes
- high dose steroids
- cyclizine
- levopromazine
Common syndromes N/V: movement associated emesis / Vestibular
-
Causes:
- Opioids
- Gut distortion
- Gastroparesis
- vestibular disorders
-
Key features:
- nausea or sudden emesis with movement/turning head
-
Pathway and receptor:
- Vestibular afferents H1, AchM
- Gut mechanoreceptors —> vagal afferents —> VC H1, Ach1
-
Treatment:
- underlying cause
- NG aspiration in terminal gastoparesis
- cyclizine
- hyoscine hydrobromide
- prochlorperazine
Common syndromes N/V: anxiety
-
Causes:
- anxiety
- anticipatory emesis (classical conditioning)
-
Key features:
- waves of nausea and vomiting
- reminders trigger nausea
- relieved by distraction
-
Pathways and receptors
- Cortex –> VC H1, ACHM
-
Treatment
- Address the anxiety
- psychological techniques
- benzos
- Amitriptyline
Common syndromes N/V: Upper GI tract causes
-
Causes:
- Glossopharyngeal nerve and vagus nerve irritation
- Pharyngeal irritation
- tenacious sputum
- candida infection
- AIDS: CMV/herpes simplex
-
Key features:
- cough, gag, sputum
- mucositis, sores
-
Pathways and receptors:
- vagal afferents –> VC
-
Treatments
- treat infection
- cough–> PPI, local anesthetic
- sputum : nac or saline nebs
Causes of drug induced nausea
-
CRTZ:
- Opioids
- Digoxin
- Anitcoagulants
- cytotoxics
- imidazoles
- antibiotics
-
GI irritation
- NSAIDS
- Iron
- antibiotics
- cytotoxics
-
Gastric stasis
- tricyclics
- phenothiazines
- opioids
- anticholingerics