Nausea and Vomiting

25-30%

PONV occurs in __-__% of post-op patients

70-80%

n/v is experienced by ___-___% of chemotherapy patients.

80%

_____% of pregnant females experience nausea

40%

___% of patients experience nausea with opioid use

15-25%

____-____% of patients experience vomiting with opioid use

nausea

unpleasant, painless sensation that one may vomit

vomiting

the ejection or expulsion of gastric contents through the mouth and is often a forceful event

hyperemesis gravidarum

severe form of nausea and vomiting during pregnancy that leads to dehydration, electrolyte imbalance, nutritional deficiencies, and weight loss

1. headaches

2. motion sickness

3. viral infections (norovirus, rotavirus)

4. heart attack

5. alcohol poisoning

6. abdominal sources

7. food poisoning

8. medicines

9. pregnancy

list some common causes of n/v.

retching

labored movement of the abdominal and thoracic muscles before vomiting

1. nausea: need to vomit

2. retching: labored movement of the abdominal and thoracic muscles before vomiting

3. vomiting: forceful expulsion of gastric contents through the mouth caused by GI retroperistalsis

what are the 3 phases of emesis?

1. 5-HT3 receptors

2. NK1 receptors

3. dopamine receptors

receptors in the CTZ

1. H1 receptors

2. M1 receptors

3. NK1 receptors

4. 5-HT3 receptors

what are the receptors in the vomiting center (Nucleus of tractus solitarius)

1. anticipatory n/v (ANV)

2. experiencing CNIV with prior chemotherapy cycles

3. anxiety before receiving chemotherapy

Risk factors for CINV (chemotherapy-induced)

1. combination of chemoradiotherapy

2. prior CINV

3. upper abdomen radiation therapy

4. field size

Risk factors for RINV (radiation-induced)

1. # of miscarriages

2. # of gravidity (pregnancies)

3. age

4. twin births

Risk factors for pregnancy-induced n/v

1. age less than 50

2. female

3. nonsmoker

4. history of PONV or motion sickness

Patient-related risk factors for PONV.

1. general anesthesia

2. volatile anesthetics

3. nitrous oxide use > 1 hour

4. opioids (during or post-op)

Anesthesia-related risk factors for PONV.

1. type of surgery

2. duration

surgery-related risk factors for PONV

1. odors

2. tastes

3. sights

4. thoughts of chemotherapy

triggers for anticipatory nausea and vomiting

1. CINV with prior chemotherapy

2. anxiety before receiving chemotherapy

risk factors for anticipatory n/v.

14%

Anticipatory n/v occurs in ____% of patients by the 3rd cycle of chemotherapy

simple symptoms of n/v

n/v that is self-limiting, resolves spontaneously, and requires only symptomatic therapy

complex symptoms of n/v

n/v that is not relieved after an antiemetic; patient deterioration due to fluid-electrolytes imbalances; associated with noxious agents or psychogenic events

weight loss, fever, abdominal pain

complex signs of n/v

serum electrolyte concentrations, upper/lower GI evaluation

laboratory tests that should be run on patients with complex n/v

1. relaxation

2. guided imagery

3. biofeedback

4. acupuncture

5. systemic desensitization

6. hypnosis

7. yoga

8. ginger

9. cognitive distraction

10. transcutaneous electrical stimulation

11. BRAT diet [bland food: bananas, rice, applesauce, toast]

12. optimism

13. chewing gum

list some non-pharmacological treatments for n/v.

Magnesium hydroxide

Aluminum hydroxide

Calcium carbonate

list some Antacids used for n/v

- usually 15-30 mL every 2-4 hours as needed.

diarrhea

what is a common ADR of magnesium-containing antacids?

constipation

what is a common ADR of aluminum and calcium-containing antacids?

neutralized HCl in the stomach; increases pH of the stomach

what is the MOA of antacids?

- Magnesium hydroxide

- Aluminum hydroxide

- Calcium carbonate

- use with caution in patients with acute or chronic kidney disease

- beware of acid base imbalances

what are some complications with the use of antacids?

Block muscarinic and histamine receptors in VC and vestibular system and reduce N/V sensation

what is the MOA of antihistaminic-anticholinergic agents?

antihistaminic-anticholinergic agents

self-care treatment to prevent n/v associated with motion sickness or vertigo

•Dimenhydrinate (Dramamine)

•Diphenhydramine (Benadryl)

•Hydroxyzine (Vistaril [pamoate caps], Atarax [hydrochloride tabs])

•Meclizine (Bonine, Antivert)

•Scopolamine (Transderm Scop)

•Trimethobenzamide (Tigan)

list some antihistaminic-anticholinergic agents.

Drowsiness

Confusion

Blurred Vision

Dry mouth

Urinary retention

list some ADRs of antihistaminic-anticholinergic agents.

BPH

narrow angle glaucoma

asthma

list some complications with antihistaminic-anticholinergic agents.

50-100 mg Q 4-6 hours PRN; liquid/oral

what is the usual dosing and formulations available for Dimenhydrinate (Benadryl)?

25-50 mg Q4-6h PRN

10-50 mg Q2-4h PRN

Tablets, capsules, liquid, IM, IV

what is the usual dosing and formulations available for Diphenhydramine (Benadryl)?

25-100 mg Q4-6h PR; tablets, capsules

what is the usual dosing and formulations available for Hydroxyzine (Vistaril, Atarax)?

12.5 - 25 mg 1 hour before travel, repeat Q12-24h PRN; tablet, chewable tablet

what is the usual dosing and formulations available for Meclizine (Antivert)?

1.5 mg Q72h; transdermal patch

what is the usual dosing and formulations available for Scopolamine (TransdermScop)?

300 mg 3-4x/d [capsule] or 200 mg 3-4x/d [IM]

what is the usual dosing and formulations available for Trimethobenzamide (Tigan)?

Histamine (H2) Antagonists

- Famotidine (Pepcid AC): 10 mg BID PRN

- Nizatidine (Axid AR): 75 mg BID PRN

- Cimetidine (Tagamet HB): 200 mg BID PRN [P450 inhibitor; many drug interactions; not to recommend first]

medications used to treat nausea secondary to heartburn or GERD by decreasing gastric acid production

5-HT3 Antagonists

- Granisetron (Sancuso, Sustol)

- Ondansetron (Zofran)

- Palonosetron (Posfrea)

- Ramosetron

- Tropisetron

What is the standard of care in CINV, PONV, and RINV?

Granisetron (Sancuso, Sustol)

Ondansetron (Zofran)

Palonosetron (Posfrea)

Ramosetron

Tropisetron

List the 5-HT3 receptor antagonists used to treat CINV, PONV, and RINV

- MOA: block serotonin receptors on sensory vagal fibers in the gut wall

- blocks acute phase of CINV but not completely

asthenia (lack of energy), constipation, headache

list the ADRs associated with 5-HT3 receptor antagonists for the treatment of CINV, PONV, and RINV.

Granisetron (Sancuso, Sustol)

Ondansetron (Zofran)

Palonosetron (Posfrea)

Ramosetron

Tropisetron

16 mg

what is the max amount of Ondansetron (Zofran) that can be given IV?

- risk of QTc prolongation

Palonosetron (Posfrea)

which 5-HT3-RA has the lowest incidence of QTc prolongation?

apply patch 24-48 hours prior to chemotherapy and wear for 7 days.

How should a patient be counseled to use Granisetron (Sancuso)?

ADRs:

- headache, constipation, diarrhea

Complications:

- drug interactions with oral chemo agents

List some ADRs and complications associated with H2 antagonists.

- Famotidine (Pepcid AC)

- Nizatidine (Axid AR)

- Cimetidine (Tagamet HB)

ANV as adjunctive therapy

what type of nausea are BZDs used for?

Lorazepam (Ativan) 0.5 - 2 mg the night before and morning of chemotherapy

what is the dose for Lorazepam (Ativan) used for ANV as adjunctive therapy?

1. dizziness

2. sedation

3. appetite changes

4. memory impairment

list the ADRs for BZDs

1. contraindicated with Olanzapine (Zyprexa) [atypical antipsychotic]

2. additive sedation with narcotic analgesics

what are some complications with use of BZSs?

1. Lorazepam

2. Oxazepam

3. Temazepam

which BZDs are preferred for the elderly?

Blocks dopaminergic stimulation of the CTZ, which in turn decreases the incidence of N/V

what is the MOA of butyrophenones?

breakthrough CINV and PONV

what are the butyrophenones used for?

- Haloperidol (Haldol)

- Droperidol (Inapsine)

Haloperidol (Haldol)

- 0.5-2 mg Q4-6 hours PRN

- tab, liquid, IM, IV

- NOT first-line for uncomplicated n/v; used for breakthrough CINV and palliative care

Droperidol (Inapsine)

- 2.5 mg; additional 1.25 mg may be given

- IM, IV

- rescue for PONV

list the butyrophenones for breakthrough CINV and PONV. what are their doses?

sedation, constipation, hypotension, extrapyramidal symptoms (EPS)

list some ADRs with Haloperidol (Haldol)

Benztropine (Сοgеntin)

what medication is used to treat EPS associated with use of Haloperidol (Haldol)?

QTc prolongation, torsade de pointes

- 12 lead electrocardiogram prior to administration

- Then cardiac monitoring for 2-3 hrs after administration

list the ADRs of Droperidol (Inapsine).

Dexamethasone (Decadron) 12 or 20 mg

Corticosteroids that are used as a single agent or in combination with 5-HT3-RAs for prophylaxis of CINV or PONV

osteoporosis

what is a risk in using corticosteroids in females?

insomnia, GI symptoms, agitation, appetite stimulation, HTN, hyperglycemia, fluid retention, psychosis

list some ADRs associated with the use of corticosteroids

false; Due to the possibility of psychosis associated with the use of corticosteroids, they are not indicated for simple n/v

T/F: Corticosteroids are used to treat simple n/v.

Chlorpromazine (Thorazine)

- 10-25 mg Q4-6h PRN; 25-50 mg Q4-6h PRN

- tab, liquid, IV

Prochlorperazine (Compazine)

- 5-10 mg Q3-4 or Q4-6h PRN; 2.5-10 mg Q3-4h PRN; 25 mg BID PRN

- tab, liquid, IM, IV, suppository

Promethazine (Phenergan)

- 12.5 mg Q4-6h PRN

- tab, liquid, IM, IV, suppository

list the phenothiazines used to treat simple n/v or breakthrough CINV

- block dopamine receptors in the CTZ

true

T/F: IV administration of Prochlorperazine (Compazine) is faster and provides more relief with less than Promethazine.

prolonged QTc, constipation, dizziness, tachycardia, tardive dyskinesia, drowsiness

List the ADRs associated with the use of the phenothiazines, Chlorpromazine (Thorazine), Prochlorperazine (Compazine), and Promethazine (Phenergan)

blocks the interaction of substance P at the neurokinin-1 receptors, preventing stimulation of CINV

What is the MOA of the NK-1 receptor antagonists?

- Aprepitant (Emend [PO], Cinvanti [IV])

- Fosapreitant (Emend [IV])

- Fosnetupitant-palonsetron (Akynzeo [IV])

- Netupitant-palonsetron (Akynzeo [PO])

- Rolapitant (Varubi [PO])

Aprepitant (Emend [capsule], Cinvanti [IV])

- capsule: 125 mg

- IV: 130 mg

Fosapreitant (Emend [IV]): 150 mg

Fosnetupitant-palonsetron (Akynzeo [IV]): 235/0.25 mg

Netupitant-palonsetron (Akynzeo [capsule]): 300/0.5 mg

Rolapitant (Varubi [capsule]): 180 mg

List the NK-1 receptor antagonists that are used in combination for prophylaxis of CINV and PONV.

- may cause: constipation, diarrhea, hiccups, dyspepsia, fatigue

CYP3A4 inhibitor and CYP2C9 inducer; interacts with some chemotherapy and estrogen contraceptives

What limits the use of Aprepitant (Emend [capsule], Cinvanti [IV])?

Fosapreitant (Emend [IV]): 150 mg

which NK-1 antagonist is given on the day of chemotherapy for CINV prevention and has fewer interactions compared to other drugs in its class?

Rolapitant (Varubi [capsule]): 180 mg

NK-1 antagonist with a long half-life of 7 days, which it allows it to be administered once weekly; has drug interactions with some chemotherapy agents due to its activity with p-glycoprotein/ABCB1 and CYP2D6; can cause hypersensitivity reactions (anaphylaxis and shock), so patients should be tested for allergen before use (soybeans and legumes)

Metoclopramide (Reglan)

10-20 mg (0.5-2 mg/kg) QID

antiemetic that blocks dopaminergic receptors centrally in the CTZ and increases LES tone, which aids in gastric emptying and accelerates transit through the small bowel; used to treat n/v associated with diabetic gastroparesis

- ADRs: asthenia, headache, somnolence, and EPS (use with caution in combo with DA agonists Olanzapine or Haloperidol)

prophylaxis not recommended

For those at a "low risk" for PONV (10%), what prophylactic therapy should be used?

2 drug regimen

For those at a "moderate risk" for PONV (1-2 risk factors), what prophylactic therapy should be used?

3-4 antiemetics from different classes

For those at a "highest risk" for PONV (>2 risk factors), what prophylactic therapy should be used?

Ondansetron (Zofran)

What is the gold standard for PONV prophylaxis?

Amisulpride (Βаrhemѕуѕ)

which antiemetic used for PONV prophylaxis can lead to an increase in prolactin levels?

Droperidol (Inapsine)

which antiemetic used for PONV prophylaxis is at an increased risk of sudden cardiac death?

prior evening or 24 hours before

When should the Scopolamine patch be applied for prophylactic PONV?

Amisulpride (Βаrhemѕуѕ) 5 mg IV

Aprepitant (Emend) 40 mg PO

Dexamethasone (Decadron) 4-8 mg IV

Palonosetron (Posfrea) 0.075 mg IV

Promethazine (Phenergan) 6.25 mg IV

which antiemetics should be administered at induction for prophylaxis of PONV?

Droperidol (Inapsine) 0.325 mg IV

Granisetron 0.35-3 mg IV

Ondansetron (Zofran) 4 mg IV or 8 mg PO/ODT

which antiemetics should be administered at the end of surgery for PONV?

give a different class than first line: phenothiazine, Metoclopramide, or Droperidol

- repeating prophylactic agents withing 6 hours has no additional benefit

if a patient experiences PONV after receiving prophylactic treatment, what should be administered?

Low dose of 5-HT3-RA (ondansetron)

- alternative low dose: Haloperidol (Haldol), Amisulpride (Βаrhemѕуѕ), Droperiol (Inapsine), or Promethazine (Phenergan)

if patient experiences PONV and no prophylactic treatment was administered, what should be administered to them now?

1. no antiemetic

2. may use 5-HT3-RA or Dexamethasone

what is used to treat PONV in children with no risk factors?

5-HT3-RA + Dexamethasone

what is used to treat PONV in children with medium risk factors (1-2)?

5-HT3-RA + Dexamethasone + Total IV anesthesia

what is used to treat PONV in children with high risk factors (3-4)?

Scopolamine (Transderm Scop)

anticholinergic used for motion sickness, vertigo, and dizziness that is applied behind the ear and worn for 72 hours

1. prenatal vitamin: start 1-3 months prior to pregnancy (folic acid in prenatals can help reduce the risk of birth defects in the first trimester)

2. dietary changes: eating frequent small meals; avoid spicy foods and odors

3. ginger: helps with nausea NOT vomiting

- 500-1000 mg 3-4 times/day

4. pyridoxine (B6) with or without doxylamine [doxylamine can cause drowsiness]

- pyridoxine: 10-25 mg PO 3-4 times/day

- doxylamine: 20-40 mg PO daily

- pyridoxine/doxylamine DR tab [Diclegis]: 20/20 mg PO QHS

- pyridoxine/doxylamine ER tab [Bonjesta]: 20/20 mg PO QHS

List some management strategies for nausea and vomiting in pregnant women.

1. IV hydration with thiamine (B1)

2. Ondansetron (Zofran)

3. Metoclopramide (Reglan)

4. Methylprednisolone: LAST RESORT; must be after 10 weeks gestation due to the incidence of causing a cleft palette

For persistent nausea and vomiting or dehydration in pregnancy, what is recommended?

10 weeks

Methylprednisolone should not be used in pregnant women before _____ weeks gestation due to the incidence of causing a cleft palette.

<2 years

Promethazine (Phenergan) is contraindicated in patients < ____ years of age due to the incidence of respiratory depression

Ondansetron (Zofran)

which antiemetic is preferred in the geriatric population?