Chapter 21: Nausea and Vomiting

-Chlorpromazine

-Prochlorperazine (Compro)

-Promethazine (Phenergan)

-Metoclopramide (Reglan)

-Trimethobenzamide (Tigan)

Dopamine antagonists

5-HT3 receptors, Dopaminergic (D2), Neurokinin-1 (NK1)

What are the Chemoreceptor Trigger Zone receptors?

Nausea

the unpleasant subjective feeling of the need to vomit

Vomiting (emesis)

a forceful oral expulsion of upper GI contents

- Chemoreceptor Trigger Zone

- Gastrointestinal Tract

- Vestibular Apparatus

- Pharynx (gag)

- Cerebral cortex

What plays a role in sending signals to the vomiting center?

Muscarinic Receptor + Histamine Receptor

What are the receptors in the vestibular system?

serotonin; visceral vagal nerve fibers are rich in 5-HT3 receptors respond to GI distention, mucosal irritation, and infection

what receptors are in the Gastrointestinal Tract?

anticipatory

The cerebral cortex is affected by sensory input such as sights, smells, or emotions that can lead to vomiting. This area is involved in _____ n/v associated with chemotherapy.

Simple N/V

Occurs occasionally and is either self-limiting or relieved by minimal therapy

Complex N/V

Requires more aggressive therapy because electrolyte imbalances, dehydration, and weight loss may occur

Mechanical obstruction

Achalasia

Enteric infection

Pancreatitis

Inflammatory bowel disease

Irritable bowel syndrome

Cholecystitis

Hepatitis

Gastroparesis

GERD

PUD

Peritonitis

GI or Intraperitoneal causes of n/v.

Cardiomyopathy

MI

Heart failure

Cardiac causes of N/V

Vestibular disease

Motion sickness

Labyrinthitis

Migraine

Intracranial pressure

Meningitis

Hydrocephalus

Eating disorder

Depression

Anxiety

Neurologic causes of N/V

Antibiotics

Antiarrhythmics

Aspirin

Chemotherapy

Digoxin

Iron

Lead

Marijuana

Oral contraceptives

Oral antidiabetics

Opioids

Anticonvulsants

Radiation therapy

Ethanol

Therapeutic causes of N/V

Pregnancy (NVP or hyperemesis gravidarum)

DKA

Hyperthyroidism

Addison disease

Parathyroid disease

Endocrine/Metabolic causes of N/V

Post Operative N/V (PONV)

Nausea that occurs in 30% of surgical patients

- 70% to 80% in high-risk patients

-Female

-Age less than 50 years of age

-History of motion sickness or PONV

-Nonsmoker

-Hydration status

-Type of anesthesia (general, volatile, nitrous oxide, opioid use)

-Duration/type of surgery

Risk factors for PONV

teratogenic effects

- Recommendations include eating frequent, small meals; avoiding spicy or fatty foods; eating high-protein snacks; avoiding iron-containing pills; and eating bland or dry foods the first thing in the morning.

Nonpharmacologic approaches to nausea and vomiting include dietary, physical, and psychological measures. Dietary management is important when treating NVP due to concern for _______ effects with drug therapies.

Acute CINV

within 24 hours after chemotherapy

Delayed CINV

more than 24 hours after chemotherapy

Anticaptory CINV

prior to chemotherapy when acute or delayed N/V occurred in previous courses

Breakthrough CINV

emesis occurring despite prophylactic administration

Refractory CINV

poor response to antiemetics

-Poor emetic control with prior chemotherapy

-Sex: Female

-Younger age

-Low chronic alcohol intake

Risk factors for CINV

Hyperemesis Gravidarum

Severe vomiting resulting in hypovolemia and weight loss during pregnancy

Management of patients with nausea and vomiting of pregnancy (NVP) depends upon:

-Symptom severity

-Impact of their symptoms on their health and quality of life

-Safety of treatment for both them and their fetus.

Nausea and vomiting can be caused by disturbances of the vestibular system in the inner ear, such as:

-Motion

-Infection

-Trauma

-Neoplasm

C. History of motion sickness

Which of the following is considered as a risk factor for developing postoperative nausea and vomiting?

A. Use of local anesthetics

B. Positive smoking history

C. History of motion sickness

D. Age >70 years old

-Diaphoresis

-Pallor

-Faintness

-Salivation

Symptoms of N/V

-Malnourishment

-Weight loss

-Dehydration (dry mucous membranes, skin tenting, tachycardia, and lack of axillary moisture)

Signs of N/V

-Electrolytes

-Acid-base disturbances

-BUN

-BUN:SCr ratio (20:1)

-Serum chloride (low)

-Serum BiCarb (high)

-Hypokalemia

Laboratory Tests involved in N/V

-Relieve the symptoms of N/V

-Increase quality of life

-Prevent complications such as, dehydration and malnutrition

Primary goal of N/V treatment

-First identify and treat the underlying cause

-Patients must have adequate hydration and electrolyte replacement orally or IV

-Drug therapy should be safe, effective, and economical

Key Concepts to general treatment approach

-Dietary management

-Avoid fatty, fried, spicy foods

-Eat food cool or at room temperatures

-Sip liquids throughout the day (cold/clear)

-Avoid triggers

-Psychological measures

-Deep breathing

-Relaxation

Non-pharmacological therapy for N/V

C. Using ginger

An appropriate nonpharmacologic recommendation for a pregnant patient with nausea and vomiting includes:

A. Eating large meals

B. Eating two times a day

C. Using ginger

D. Smelling trigger odors

Blocks the action of acetylcholine at parasympathetic sites in the CNS (vestibular system)

Scopolamine (Transderm Scop®) MOA

Most common: dry mouth, drowsiness, blurred vision

Rare: disorientation, dizziness, hallucinations

Adverse Effects of Scopolamine (Transderm Scop®)

Effective for preventing and treating motion sickness and has some efficacy in preventing PONV

Scopolamine (Transderm Scop®) role in therapy

72 hours

Scopolamine is available as an adhesive transdermal patch that is effective for up to ____ hours after application

-Adverse effects are worsened when a patient is taking concurrent anticholinergic agents

-On the Beers Criteria list, avoid in elderly

-Monitor body temperature, heart rate, urinary output, intraocular pressure, mental alertness

Monitoring Parameters for Scopolamine (Transderm Scop®)

antihistamines

used to prevent and treat nausea and vomiting due to motion sickness, vertigo, or migraine headache.

- efficacy is presumably due to the high concentration of H1 and muscarinic cholinergic receptors within the vestibular system

Competes with histamine for H1-receptor sites, blocking chemoreceptor trigger zone, diminishing vestibular stimulation, and depressing labyrinthine function through its central anticholinergic activity

Antihistamines MOA

Most common: Sedation, dry mouth, constipation

Less common: confusion, blurred vision, urinary retention

Adverse Effects of antihistamines

Prevent and treat N/V due to motion sickness, vertigo, or migraine headache

Antihistamines role in therapy

-Relief of symptoms

-Mental alertness

Antihistamines monitoring parameters

-Dimenhydrinate (Dramamine®)

-Diphenhydramine (Benadryl®)

-Doxylamine (Sleep Aid®)

-Hydroxyzine (Vistaril®)

-Meclizine (Antivert®, Bonine®)

Antihistamines used for N/V

1. phenothiazines

2. butyrophenones

3. prokinetic agents

what are the 3 main groups of dopamine antagonists?

act primarily via a central anti-dopaminergic mechanism in the CTZ

where do phenothiazine dopaminergic antagonists work?

Act primarily via a central antidopaminergic (D2 receptors) mechanism in the chemoreceptor trigger zone

Chlorpromazine and Prochlorperazine MOA (Phenothiazine)

-Most common: sedation, lethargy, skin sensitization

-Less common: orthostatic hypotension, EPS (dystonia or tardive dyskinesia), jaundice, gynecomastia/hyperprolactinemia

Chlorpromazine and Prochlorperazine adverse effects

Increased mortality in elderly patients with dementia-related psychosis

Chlorpromazine and Prochlorperazine BBW

Treat N/V in the setting of severe motion sickness/vertigo, gastritis or gastroenteritis, NVP, PONV, and CINV

Chlorpromazine and Prochlorperazine role in therapy

-Mental status

-Weight (BMI/WC)

-Fasting plasma/A1c

-Abnormal movements

Chlorpromazine and Prochlorperazine monitoring parameters

Act primarily via a central antidopaminergic (D2 receptors) mechanism in the chemoreceptor trigger zone

Promethazine (Phenergan) MOA

intra-arterially

Promethazine intravenous injection should not be administered in an undiluted bolus because this may lead to tissue necrosis requiring limb amputation.20 The highest risk for this adverse event is when the medication is administered _______

Respiratory depression in pediatric patients 2 years and younger; severe tissue injury (gangrene)

Promethazine (Phenergan) BBW

Treat NV in the setting of severe motion sickness/vertigo, gastritis or gastroenteritis, NVP, PONV

Promethazine (Phenergan) role in therapy

Dopamine antagonists cont

-Droperidol

-Haloperidol

Act primarily via a central antidopaminergic (D2 receptors) mechanism in the chemoreceptor trigger zone

Droperidol and Haloperidol MOA

(butyrophenone)

-Most common: sedation, hypotension, tachycardia

-Less common: increased blood pressure, chills, hallucinations, QT prolongation

Droperidol adverse effects

Arrythmia (QT prolongation) that may lead to torsades de pointes and sudden cardiac death

Droperidol BBW

Effective in preventing PONV and can also be used for treating CINV for patients who are intolerant to serotonin receptor antagonists and corticosteroids.

Droperidol role in therapy

-12 lead ECG must be performed before initiating therapy

-Magnesium and potassium levels

-Mental status

-EPS

Droperidol monitoring parameters

Haloperidol monitoring

-12 lead ECG must be performed before initiating therapy

-Magnesium and potassium levels

-Mental status

Tardive dyskinesia

Metoclopramide (Reglan) BBW

Effective in PONV, CINV, gastroparesis, and GERD

Metoclopramide (Reglan) role in therapy

-Signs of EPS and tardive dyskinesia

-Signs of neuroleptic malignant syndrome (high fever, sweating, unstable blood pressure, irregular heartbeat)

Metoclopramide (Reglan) monitoring

A. Scopolamine

Which of the following medications would be considered first line in the prevention of nausea and vomiting related to motion sickness?

A. Scopolamine

B. Ondansetron

C. Cetirizine

D. Ginger

-Dexamethasone

-Methylprednisolone

Corticosteroids used in N/V

Most common: GI upset, anxiety, insomnia, hyperglycemia, insomnia

Less common: Decreased bone mineral density, diabetes, cataracts

Corticosteroids adverse effects

used alone or in combination with other antiemetics for preventing and treating PONV, CINV, or radiation-induced nausea and vomiting

- efficacy is thought to be due to release of 5-HT, reduced permeability of the blood-brain barrier, and decreased inflammation

Corticosteroids role in therapy

-BP

-Glucose

-Bone mineral density

Corticosteroids monitoring

-Dronabinol (Marinol®)

-Nabilone

Cannabinoids used for n/v

Most common: Drowsiness, euphoria, somnolence, vasodilation, vision changes

Less common: Diarrhea, tremor

Cannabinoids adverse effects

Preventing and treating refractory or delayed CINV

Cannabinoids role in therapy

BP

HR

Abuse/misuse

Cannabinoids monitoring

Lorazepam, Alprazolam

Benzodiazepines used in N/V

Most common: Drowsiness, euphoria, somnolence, vasodilation, vision changes

Less common: Diarrhea, tremor

Benzodiazepines adverse effects

Preventing and treating refractory or delayed CINV

Benzodiazepines role in therapy

Respiratory and CV status

BP/HR

Benzodiazepines monitoring

-Increased risk of CNS depression with concomitant use with opioids

-Abuse/misuse/addiction

-Dependence and withdrawal

Benzodiazepines BBW

-Dolansetron (Anzemet)

-Odansetron (Zofran)

-Granisetron (Sancuso)

-Palonosetron

Selective -HT3 receptor antagonists

Selective 5-HT3 antagonists stimulate receptors triggered by the CTZ

Selective-HT3 receptor antagonists) MOA

Prevent and treat N/V due to stimulation of 5HT3 receptors for CINV and PONV

Selective-HT3 receptor antagonist role in therapy

Most common: headache, QT prolongation

Less common: constipation, somnolence, nervousness

Selective-HT3 receptor antagonist adverse effects

ECG

Serum potassium and magnesium

Monitor for signs and symptoms of serotonin syndrome

Selective-HT3 receptor antagonist monitoring

Palonosetron

the first 5-HT3 antagonist to be approved for preventing both acute and delayed CINV.

- Compared to other 5-HT3 antagonists, it has a longer serum half-life (40 hours compared to 4-9 hours) and a higher receptor-binding affinity, which may contribute to its efficacy in preventing delayed CINV.

Aprepitant

Rolapitant

Netupitant (only in combination with Palonosetron under the brand name Akynzeo)

Neurokinin-1 Antagonists

Prevents delayed N/V associated with emetogenic chemotherapy by selectively and competitively inhibiting the substance P/neurokinin 1 (NK1) receptor

Neurokinin-1 Receptor Antagonists MOA

-Most common: Fatigue, hiccups

-Less common: dizziness, headache, insomnia

-Rare: Transient elevations in hepatic transaminases

Neurokinin-1 Receptor Antagonists adverse effects

CYP 3A4

Aprepitant has numerous drug interactions because it is an inhibitor and substrate of the _____ metabolic pathway.

Aprepitant

first NK1 receptor antagonist antiemetic that is effective in preventing acute and delayed CINV when used with a 5-HT3 antagonist and corticosteroid; also effective for PONV

Netupitant/Palonosetron (Akynzeo) monitoring

Inhibitor and substrate of CYP3A4

Hepatic function

Olanzapine (Zyprexa)

an antipsychotic agent that has effects at D2, 5-HT2c, and 5-HT3 receptors; recommended to be used in combination therapy for prevention of CINV in patient receiving highly emetogenic chemotherapy

Sedation

Olanzapine (Zyprexa) side effect/monitoring

Cisplatin

High-dose Cyclophosphamide (1.5 g/m2 or more)

Cyclophosphamide combined with an Anthracycline

Chemotherapeutic agents are classified according to their emetogenic potential, which aids in predicting CINV. What are some chemotherapeutic agents with high emetogenic potential?

5-HT3 antagonist or an 8-mg dose of dexamethasone

Patients receiving chemotherapeutic agents with low emetogenic potential should receive a single dose of a _____ or _____ as CINV prophylaxis, and those receiving chemotherapy with minimal emetogenic risk do not require prophylaxis

cisplatin and cyclophosphamide

Delayed nausea and vomiting is more difficult to prevent and treat. It occurs most often with ______ and _____ regimens, especially if delayed nausea and vomiting occurred with previous chemotherapy courses.8 Patients who had poorly controlled acute CINV in the past are at greatest risk for delayed CINV

High emetogenic chemotherapy regimen

Four - drug regimen (NK1 antagonist, 5HT3 antagonist, dexamethasone, and olanzapine)

Moderate emetogenic chemotherapy regimen

Two - drug regimen (5HT3 antagonists and dexamethasone)