Nausea and Vomiting Flashcards
Three phases of emesis
Nausea • Subjective feeling of “impending vomiting”
Retching • Spasmodic contractions of the diaphragm and intercostal muscles (“respiratory muscles”) with
epiglottis closed
Vomiting • Oral expulsion of GI contents
order the emetic sequence
2 Peristalsis reverses direction: • pushes stomach contents out of mouth. 3 Epiglottis closed to prevent pulmonary aspiration 4 Contraction of diaphragm + abdominal muscle. 5 Soft palate is raised to prevent GI contents going into nasopharynx. 6 Relaxation of lower esophageal sphincter.
Contraction of diaphragm + abdominal muscle. – Relaxation of lower esophageal sphincter. – Peristalsis reverses direction: • pushes stomach contents out of mouth. – Soft palate is raised to prevent GI contents going into nasopharynx. – Epiglottis closed to prevent pulmonary aspiration.
Aspiration pneumonia, choking
when food, saliva, liquids, or vomit is breathed into the lungs or airways leading to the lungs, instead of being swallowed into the esophagus and stomach
Central regulation of vomiting occurs in two separate
areas of the medulla:
• Emetic center (vomiting center), medulla oblungata
– Mediates vomiting from all causes
– Coordinates the respiratory, GI and abdominal musculature involved in vomiting
Nucelus of cells in medulla Recognizes signals
• Chemoreceptor trigger zone (CTZ), area postrema
– Activate the emetic center
– Responds to blood borne endogenous or exogenous
molecules that activate emesis
4th ventricle, near brainstem
Slightly out of BBB so responds to circulation
describe the Vestibular apparatus pathway
– Labyrinth stimulation of vestibular cochlear nerve (cranial nerves VIII)
– Stimulates vestibular nuclei in brain stem – contain histamine and
muscarinic (Ach) receptors
– Ach receptors – activate emetic center
– NA receptors – stabilize emetic center
Stimulus from innter ear to brain
describe cortical stimulation and visceral stimulation
• Cortical stimulation (cognitive)
– Emotions, smells, taste, sight
Panic, anxiety Stimulate cerebral cortex
Noxious smell
• Visceral stimulation
– Autonomic afferents from pharynx and GI
– MI, appendicitis
Internal organs
Specially coming from GI tract
Appendicitis, heart attachk can stimulate it to happen
• Emetic reflex involves multiple receptor (7):
Serotonin (5-HT3) Dopamine (D2) Acetylcholine (Ach, muscarinic, M1) Histamine (H1) Cannabinoid (CB1) Neurokinin-1 (NK-1) – substance P Opioid
Causes of Nausea and Vomiting
• Motion sickness • NV of pregnancy • Postoperative • Medications • Disease – Infections – Cardiac – Gastrointestinal – Metabolic/endocrine causes – Central Nervous System – Psychiatric
Approach to NV
Three step approach:
1. Recognize and correct any consequences of the
vomiting e.g. dehydration, electrolyte abnormalities
2. Identify underlying cause for NV.
3. Treat underlying cause. If no etiology can be
determined use empiric therapy to treat symptoms.
Assessment of NV
• Assess patients signs and symptoms: – Severity of NV – Onset and frequency of NV – Appearance vomited material – Aggravating or remitting factors – Associated symptoms: fever, abdominal pain, weight loss, diarrhea, headache/migraines etc.
red flags
Symptoms of dehydration – Persistent vomiting – Blood or “coffee-grounds” in vomitus – Blood in stools (black or tarry) – Difficulty swallowing – Abdominal pain – Weight loss (unintended) – Altered mental status – Age >55 years
• Types of physical examination:
Suken eyes, low urine ouput, dry mouth, lips, stringy saliva, dry mucous membranes, thirsty headache
Sunken eyes in children, decrease in skin turgor, stays elevated when pinched
– Abdominal examination – Neurologic examination – Signs of psychiatric cause • General examination/diagnostic tests to rule out potential causes and/or complications
Complications of Vomiting
• Fluid, electrolyte and metabolic alterations.
– Dehydration, hypotension, hemoconcentration, oliguria, muscle weakness, cardiac arrhythmias
• Aspiration pneumonia
• Prolonged vomiting:
– Nutritional deficiencies - malnutrition
– Esophagitis
– Lacerations at the gastroesophageal junction
– Multiple purpuric lesions: long durations where blood vessels on face conversed
– Dental caries/erosions
Goals of Therapy
- Relieve symptoms
- Prevent complications
- Prevent recurrence or reduce the frequency of episodes
- Improve patients quality of life
Non-pharmacologic Therapy
• General approaches:
– Adequate hydration
– Avoid noxious odors/foods that cause nausea
– Eat frequent, small meals
– Decrease physical activity
– Gear approach to cause/etiology of NV
• e.g. if labyrinthine changes produced by motion then assume stable physical position
Supportive care
Prevent and relieve symtpoms
Stable visual line for motion sickness
Maintain fluid intake
how much water?
– Depends on amount of vomiting
– Normal amounts – adults need 1 – 3 L of total water intake
• Amount required will depend on amount lost with vomiting (and/or diarrhea)
– Moderate or severe vomiting may require electrolyte replacement:
• e.g. oral rehydration solutions (OHS)
describe Acupressure
• Acupressure
– Sixth point along the pericardial meridian (P6)
– Nei Guan (“inner guard”)
– 3 - 5 minutes of pressure every 4 hours
– NV of pregnancy, motion sickness, PONV
Heart meridian
Helps with nausea
Doesnt know if it helps vomiting
Post operative nasuea vomiting
• Acupuncture
Acupressure wristbands – SeaBandsTM, others –Have not been shown to be effective in motion sickness • Less effective than manual pressure
Histamine (H1)-Receptor Antagonists
name 3 pdts and dose
• Role: management of motion sickness, vertigo, also used for many other NV
dimenhydrinate (GravolTM, generics) OTC (Schedule III) Schedule II (injectable) Oral, IM, Rectal 50 – 100 mg q4 – 6h (po, rectal, im) prn 100 mg long acting q8- 12h
diphenhydramine
(BenadrylTM, generics)
OTC Oral 25 – 50 mg q6 -8h prn
hydroxyzine (generics) Prescription Oral 25 – 100 mg bid – tid prn
ONSET is 60 minutes, taking it before travel
Histamine (H1)-Receptor Antagonists
side fx
- Note: blocks H1 receptors, but also has anticholinergic effects
- drowsiness
- confusion
- dry mouth
- blurred vision
- urinary retention
- constipation
- Elderly are increased risk of anticholinergic side effects
Muscarinic Receptor Antagonists (Anticholinergics)
• Scopolamine (Transderm-VTM) Schedule II
contra and side fx
dose and onset
• Role: motion sickness
• Side effects:
– Sedation, confusion, dry mouth, blurred vision,
constipation, rash, urinary retention
• Do not use in children (<12 years), elderly greater risk
of anticholinergic and CNS effects
• Contraindications: narrow-angle glaucoma, difficulty
with urination (i.e. prostatic hypertrophy)
Dose: 1 patch q72 hours
Onset in 4 hours
Patch behind ear for 3 days, can be applied again just on the other area that is recommended
At least 4 hours before cruise
Not for children < 12
Causes dilation of pupil dilation which can affect narrow angle glaucoma
Dopamine (D2)-Receptors Antagonists
role
types
Lots of parenteral forms
Used in hospital often
Donèt need to know dosing
• Antipsychotics:
Phenothiazines:
prochlorperazine, chlorpromazine, promethazine
Butyrophenones:
haloperidol
2nd generation antipsychotics
olanzapine
• Role: severe nausea and vomiting, NVP, PONV, AINV
Chlorpromazine (generics) IM, IV 10 – 25 mg q4 – 6h
Prochlorperazine (generics) oral, IM,IV, supp 5 – 10 mg q6 – 8h
Promethazine (HistantilTM, generics)
Schedule II for oral oral, IM, IV 25 – 50 mg q6 – 8h
Perphenazine (generic) oral 2 – 4 mg g8h prn
Haloperidol (generics) oral, IM, IV 1 – 2 mg q8h
Olanzapine oral 2.5 – 5 mg bid
Dopamine (D2)-Receptors Antagonists
Side effects
Note: in addition to blocking dopamine receptors in CTZ, also has anticholinergic and antihistamine activity
– drowsiness
– extrapyramidal symptoms (EPS) i.e. dystonic reactions (muscle contraction of face, neck), tardive dyskinesia(motion disorder),
– postural hypotension,
– dry mouth and other anticholinergic
– hyperprolactinemia
– QT interval prolongation – with butyrophenones
• Elderly more prone to EPS, anticholinergic effects
• Olanzapine may have less EP
From blocking dopamine receptors
Dopamine inhibits prolactin release
Leads to increased prolactin levels when you donèt have dopamine
Galactorrhea, breast milk discharge
Breast tenderness and enlargmeent in men and women
Dopamine (D2)-Receptors Antagonists
Benzamides
Benzimidazole derivatives
role
Benzamides: Metoclopramide
Benzimidazole derivatives: Domperidone
Metoclopramide Oral, IV 10 mg q4-6h Acts in CTZ and periphery
Domperidone Oral 10 mg qid Acts only in periphery, Does not cross blood brain barrier
Role: severe nausea and vomiting, NVP, PONV, AINV,
radiation induced
Note: metoclopramide is a more effective antiemetic as compared to domperidone. more meto used in NV
Dopamine (D2)-Receptors Antagonists
METO and DOMPERIDONE
Side effects:
– drowsiness
– extrapyramidal symptoms (EPS) (1%) – dystonic reactions, tremor, tardive dyskinesia
• elderly more prone EPS symptoms
– prolongation of QT interval – arrhythmias (domperidone)
– increase prolactin release (breast tenderness, galactorrhea)
• Domperidone – less CNS and EPS effects
– only recommended short term because of QT prolongation
Greater SE from metoclopramide b/c it crosses BBB
Usually only with loong term use
Prolong QT interval
Safety due to QT prolongation
Serotonin (5-HT3)-Receptor Antagonists
- The “setrons”: ondansetron, granisetron, palonosetron
- Role: PONV, AINV, radiation induced
see slide 39 for table
Serotonin (5-HT3)-Receptor Antagonists
Side effects:
constipation,
• headache,
• lack of energy/weakness
• risk of serotonin syndrome (rare; in combination with other
serotonergic and/or neuroleptic drugs)
• dose-dependent QT interval prolongation (rare)
Neurokinin-1 (NK-1)-Receptor Antagonists
role
name of products
• Non-peptide NK1-receptor antagonists:
– oral – aprepitant (EmendTM)
– IV form is fosaprepitant (a prodrug of aprepitant)
• Role: used in combination with 5-HT3 antagonists and
dexamethasone for AINV
• Dose: 125 mg prior to chemo, and 80 mg day 2 and 3
• Many drug interactions (inducer/inhibitor of CYP 3A4, inducer CYP 2C9)
Glucocorticoids
• Antiemetic mechanism not well understood.
• Dexamethasone – most common formulation used acutely
– 10 mg IV pre, then 4 mg q6h post x 3 doses
• Indications: PONV, AINV, radiation induced NV
• Side effects: note: usually used short term in NV, fluid and electrolytes
disturbances, hyperglycemia, infections, psychosis
• Long term: osteoporosis
Long term side eff not a concern, usually for a few days
Cannabinoids
role
side effects
• Synthetic cannabinoids (delta-9-tetrahydrocannibinol (THC)
– nabilone (CesametTM) – 1 – 2 mg bid oral
• Effects on receptors in neural tissues
– Role in AINV
– Used when refractory to other antiemetics
• Side effects: euphoria, sedation, dysphoria, hallucinations/paranoid
what evidence is shown for medical cannabis?
• Role in AINV
• Extensive studies with the synthetic cannabinoids such as nabilone approved by Health Canada (contain DIN).
• Evidence is limited with forms of medical cannabis (ie edibles, oils, vaping etc) in AINV, though few studies with THC only capsules
Note: chronic cannabinoid use is also associated with cannabinoid hyperemesis syndrome – etiology unknown
chronic use: cannabinoid hyperemesis syndrome
Can be pro emetic for indivduals for chronic use
