Nausea & Vomiting

Antonius WP. , Dhita Evi Aryani

Department of Clinical and Community Pharmacy
Faculty of Pharmacy Universitas Jember
 Referenc
• Berardi et al, 2009,eHandbook of Nonprescription Drugs :
An Interactive Approach to Self-Care, 16th Ed.
Washington: American Pharmacist Associations
• DiPiro, JT, et al. 2020. Pharmacotherapy: A
Pathophysiologic Approach. 11th ed. NY: McGraw-Hill
• Krinsky et al. 2021. Handbook of Nonprescription Drugs :
An Interactive Approach to Self-Care, 20th Ed.
Washington: American Pharmacist Associations
 KEY CONCEPTS
• Nausea and/or vomiting is often a part of the
symptom complex for a variety of gastrointestinal
(GI), cardiovascular, infectious, neurologic,
metabolic, or psychogenic processes.
• Nausea or vomiting is caused by a variety of
medications or other noxious agents.
• The overall goal of treatment should be to
prevent or eliminate nausea and vomiting
regardless of etiology
• Treatment options for nausea and vomiting
include drug and nondrug modalities suchas
relaxation, biofeedback, and hypnosis.
 KEY CONCEPTS
• The primary goal with chemotherapy-induced
nausea and vomiting (CINV) is to prevent
nausea and vomiting throughout the entire
risk period; the emetic risk of the
chemotherapeutic regimen is a major factor
to consider when selecting a prophylactic
regimen. The emetic risk of the
chemotherapeutic regimen is the primary factor
to consider when selecting prophylactic
antiemetics for CINV.
 KEY CONCEPTS
• Patients undergoing radiation therapy (RT) to the
upper abdomen or receiving total body or
craniospinal irradiation should receive prophylactic
antiemetics for radiation-induced nausea and vomiting
(RINV)
• Patients at high risk of vomiting should receive
prophylactic antiemetics for postoperative nausea and
vomiting (PONV)
• Beneficial therapy for patients with balance disorders
can most reliably be found among the antihistaminic–
anticholinergic agents
 ETIOLOG
•
Y
Associated with a variety of clinical presentations
(see tables)
• In children
– vomiting in newborn --> suggests upper digestive
tract obstruction or an increase in intracranial
pressure.
– other illnesses associated: pyloric stenosis, duodenal
ulcer, stress ulcer, adrenal insufficiency, septicemia,
and diseases of the pancreas, liver, or biliary tree.
– Reye syndrome: hepatocellular failure  profound
cerebral edema  persistent emesis.
Etiology
 PATHOPHYSIOLOGY

3 phases of EMESIS

nausea vomiting
retching

Different from
regurgitation (acid reflux)
CLINICAL PRESENTATION

Simple or

Complex?
 TREATMENT
Desired Outcomes
• Overall goal: to prevent or eliminate nausea
and vomiting
– without adverse effects or with clinically
acceptable adverse effects
– appropriate cost issues, particularly in the
management of chemotherapy-induced and
postoperative nausea and vomiting
 TREATMENT
General Approach
• Options: drug and non-drug
• Varied depending on the associated medical situation.
• Most patients receive a medication at some point
• For simple nausea and vomiting:
– do nothing or
– to select from a variety of nonprescription drugs (OTC).
• If symptoms are worse or associated with serious
medical problems:
– prescription antiemetic drugs
– However, some patients will never be totally free of
symptoms (eg: receiving chemotherapy of moderate or
high emetic risk)
 TREATMENT
Nonpharmacologic Management
• Involves dietary, physical, or psychological strategic
consistent with the etiology of symptoms.
• For patients with simple complaints, perhaps resulting
from excessive or disagreeable food or beverage
consumption, avoidance or moderation in dietary
intake may be preferable.
• Patients suffering symptoms of systemic illness may
improve dramatically as their underlying condition
resolves.
• Finally, patients in whom these symptoms result from
labyrinthine changes produced by motion may benefit
quickly by assuming a stable physical position.
 TREATMENT
Nonpharmacologic Interventions
• classified as behavioral interventions and include
relaxation, biofeedback, hypnosis, cognitive distraction,
optimism, guided imagery, acupuncture, yoga,
transcutaneous electrical stimulation, chewing gum,
and systematic desensitization.
 TREATMENT
Pharmacologic
• Most often recommended: Antiemetic drugs
(nonprescription and prescription)
• Factors that enable the clinician to discriminate
among various choices include:
– the suspected etiology of the symptoms;
– the frequency, duration, and severity of the
episodes;
– the ability of the patient to use oral, rectal, injectable,
or transdermal medications; and
– the success of previous antiemetic medications.
 TREATMENT
Pharmacologic
• Simple emesis: minimal therapy
– Both nonprescription and prescription drugs usually
effective in small, infrequently administered doses.
– Minimal side effects and toxic effects
• Prescription medications can be either as single-
agent therapy or in combination depending on px
conditions
• Complex nausea and vomiting (eg: px with
cytotoxic chemotherapy) combination therapy.
 TREATMENT
Pharmacologic
• In combination regimens, the goal is to
achieve symptomatic control through
administration of agents with different
pharmacologic mechanisms of
action.
 TREATMENT
Pharmacologic
ANTACIDS
• Single or combination nonprescription antacid
products
• magnesium hydroxide, aluminum hydroxide,
and/or calcium carbonate  gastric acid
neutralization
• Common regimens: one or more 15 to 30 mL
doses of single- or multiple-agent products
 TREATMENT
Pharmacologic
ANTACIDS
• Potential adverse effects:
– magnesium salt (osmotic diarrhea)
– aluminum/calcium salts (constipation)
• Generally, however, when used occasionally
for acute episodic relief of nausea and
vomiting, antacids do not produce serious
toxicities.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
H2-RECEPTOR ANTAGONISTS
• Low doses to manage simple emesis
associated with heartburn or
gastroesophageal reflux.
• Individual dosages of cimetidine 200 mg,
famotidine 10 mg, nizatidine 75 mg, or
ranitidine 75 mg may be used for brief
periods.
• Potential drug interactions: cimetidine
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
ANTIHISTAMINE–ANTICHOLINERGIC DRUGS
• Interupt various visceral afferent pathways that
stimulate nausea and vomiting  for simple nausea
and vomiting.
• Adverse reactions: drowsiness, confusion, blurred
vision, dry mouth, and urinary retention, and possibly
tachycardia, particularly in elderly patients.
• Patients with narrow-angle glaucoma, prostatic
hyperplasia, or asthma are at greater risk of
complications from the anticholinergic effects of these
drugs.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
PHENOTHIAZINES
• Phenothiazines have been the most widely
prescribed antiemetic agents and appear to block
dopamine receptors, most likely in the CTZ.
• Most useful in adult patients with simple nausea
and vomiting
• Most practical for long-term treatment and are
inexpensive in comparison with newer drugs.
 TREATMENT
Pharmacologic
PHENOTHIAZINES
• Many dosage forms, none of which appears to be more
efficacious than another.
– Rectal: in patients not feasible with oral or parenteral
administration
– Intravenous: quicker and more complete relief with
less
drowsiness

• Potential side effects: extrapyramidal reactions,

hypersensitivity reactions with possible liver
dysfunction, bone marrow aplasia, and excessive
sedation.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
BUTYROPHENONES
• haloperidol and droperidol
• both block dopaminergic stimulation of the
CTZ
• Although each agent is effective in relieving
nausea and vomiting, haloperidol is not
considered first-line therapy for
uncomplicated nausea and vomiting but has
been used in palliative care situations.
 TREATMENT
Pharmacologic
BUTYROPHENONES
• Current droperidol labeling: all
patients should:
– undergo a 12-lead
electrocardiogram before
administration
– cardiac monitoring for 2 to 3
hours after administration
– Reason: the possibility of the
development of potentially fatal QT
prolongation and/or torsade de
pointes.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
CORTICOSTEROIDS
• Prednisone in patients with Hodgkin disease
• Methylprednisolone, mostly in combination with
dexamethasone
• Dexamethasone: for CINV and PONV management
either as a single agent or in combination with
selective serotonin reuptake inhibitors (SSRIs).
– effective in the prevention of both cisplatin-induced
acute
emesis
– alone or in combination for the prevention of delayed
nausea and vomiting associated with CINV
 TREATMENT
Pharmacologic
CORTICOSTEROIDS
• For patients with simple nausea and vomiting,
steroids are not indicated and may be
associated with unacceptable risks.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
METOCLOPRAMIDE
• Significant antiemetic effects by blocking the
dopaminergic receptors centrally in the CTZ.
• Increases lower esophageal sphincter tone,
aids gastric emptying, and accelerates transit
through the small bowel, possibly through the
release of acetylcholine
• For patients with diabetic gastroparesis
 TREATMENT
Pharmacologic
METOCLOPRAMIDE
• With dexamethasone for prophylaxis of delayed
nausea and vomiting associated with
chemotherapy administration
• Prophylaxis for acute CINV was supplanted by the
introduction of the SSRIs in the early 1990s.
• These agents have greater efficacy and decreased
toxicity compared with metoclopramide in
patients who are receiving cisplatin-based
regimens.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
CANNABINOIDS
• Oral nabilone, oral dronabinol, intramuscular
levonantradol
• Cannabinoids were slightly more effective than active
comparators antiemetics (prochlorperazine,
metoclopramide, chlorpromazine, thiethylperazine,
haloperidol, domperidone, and alizapride) and placebo
when the chemotherapy regimen was of moderate
emetogenic potential, and patients preferred them.
• No dose–response relationships were evident
 TREATMENT
Pharmacologic
CANNABINOIDS
• The cannabinoids were also more toxic; side
effects included euphoria, drowsiness, sedation,
somnolence, dysphoria, depression,
hallucinations, and paranoia.
• The efficacy of cannabinoids as compared to
SSRIs has not been studied.
• Use of these agents should be considered when
other regimens do not provide desired efficacy.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
SUBSTANCE P/NEUROKININ 1 RECEPTOR
ANTAGONISTS
• Substance P is a peptide neurotransmitter in
the neurokinin (NK) family whose preferred
receptor is the NK1 receptor.
• The acute phase of CINV is believed to be
mediated by both serotonin and substance P,
whereas substance P is believed to be the
primary mediator of the delayed phase.
 TREATMENT
Pharmacologic
SUBSTANCE P/NEUROKININ 1 RECEPTOR ANTAGONISTS
• Aprepitant is the first substance P/NK1 receptor antagonist
in clinical use; others are in development.
• The efficacy of aprepitant was demonstrated in patients
receiving high dose cisplatin-based chemotherapy and in
patients receiving doxorubicin and cycophosphamide, a
regimen of moderate emetic risk.
• The three-drug regimen of aprepitant, dexamethasone, and
ondansetron provided improved protection from vomiting
for the 5 days after chemotherapy administration as
compared with the combination of dexamethasone and
ondansetron.
 TREATMENT
Pharmacologic
SUBSTANCE P/NEUROKININ 1 RECEPTOR ANTAGONISTS
• Aprepitant has the potential for numerous drug
interactions because it is a substrate, moderate
inhibitor, and an inducer of cytochrome isoenzyme
CYP3A4 and an inducer of CYP2C9.
• Aprepitant can increase serum concentrations of many
drugs metabolized by CYP3A4, including docetaxel,
paclitaxel, etoposide, irinotecan, ifosfamide, imatinib,
vinorelbine, vincristine, and vinblastine.
• The efficacy of oral contraceptives may be reduced
when given with aprepitant.
 TREATMENT
Pharmacologic
SUBSTANCE P/NEUROKININ 1 RECEPTOR ANTAGONISTS
• Concomitant administration with warfarin may
result in a clinically significant decrease in the
international normalized ratio.
• The dose of oral dexamethasone should be
reduced 50% when coadministered with
aprepitant, because of the 2.2-fold increase in
observed area under the plasma-concentration-
versustime curve.
• Aprepitant is not approved for use in children.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
• Blocking presynaptic serotonin receptors on sensory
vagal fibers in the gut wall, effectively blocking the
acute phase of CINV.
• Do not completely block the acute phase of CINV and
are less efficacious in preventing the delayed phase,
but are the standard of care in the management of
chemotherapy-induced, radiation-induced, and
postoperative nausea and vomiting.
• The most common side effects: constipation,
headache, and asthenia.
• Safety and efficacy in children younger than
2 yo  ?
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
CHEMOTHERAPY-INDUCED NAUSEA AND
VOMITING
• Nausea and vomiting that occurs within 24
hours of chemotherapy administration is
defined as acute, whereas when it starts more
than 24 hours after chemotherapy
administration, it is defined as delayed.
• The primary goal with CINV is to prevent
nausea and/or vomiting.
 TREATMENT
Pharmacologic
CHEMOTHERAPY-INDUCED NAUSEA AND
VOMITING
• Factors to consider when selecting an
antiemetic for CINV include the following:
– The emetic risk of the chemotherapy agent or
regimen (see Table 52–2)
– Patient-specific factors
– Patterns of emesis after administration of specific
chemotherapy agents or regimens
Emetic Risk of Agents Used in Oncology and
Treatment Options
 TREATMENT
Pharmacologic
POSTOPERATIVE NAUSEA AND VOMITING (PONV)
• Complicates surgical procedures for
approximately 25% to 30% of patients
undergoing anesthesia.
• Factors to be considered for PONV prophylaxis
and treatment include
– risk factors,
– potential morbidity,
– potential adverse events associated with
antiemetics,
– antiemetic efficacy, and
– costs.
 TREATMENT
Pharmacologic
POSTOPERATIVE NAUSEA AND VOMITING (PONV)
• Most patients undergoing an operative procedure do not
require preoperative prophylactic antiemetic therapy and
universal PONV prophylaxis is not cost-effective.
• Other strategies to reduce baseline PONV risk factors
among patients at highest risk, in addition to prophylactic
antiemetics, include use of regional anesthesia, propofol,
supplemental oxygen, and hydration, as well as avoiding
nitrous oxide, volatile anesthetics, and opioids.
• Total intravenous anesthesia reduced the risk of PONV
similar to the prophylactic administration of a single
antiemetic.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
RADIATION-INDUCED NAUSEA AND VOMITING
(RINV)
• Not well understood.
• Neither as predictable nor as severe as CINV,
• Many patients receiving radiation therapy will
not experience nausea or vomiting
 TREATMENT
Pharmacologic
RADIATION-INDUCED NAUSEA AND VOMITING
(RINV)
• Risk factors: the site of radiation, the dose,
dose rate, and area of the body to be
irradiated
• Patients receiving single-exposure, high-dose
radiation therapy to the upper abdomen, or
total- or hemibody irradiation, should receive
prophylactic antiemetics for RINV.
 TREATMENT
Pharmacologic
DISORDERS OF BALANCE
• Vertigo and dizziness
• The etiology includes diseases that are
infectious, postinfectious, demyelinative,
vascular, neoplastic, degenerative, traumatic,
toxic, psychogenic, or idiopathic
• Symptoms of imbalance perceived by the
patient present a particular clinical challenge.
 TREATMENT
Pharmacologic
DISORDERS OF BALANCE
• Beneficial therapy for patients: the
antihistaminic–anticholinergic agents
• Precise mechanisms of action of these agents are
currently unknown
• Oral regimens of antihistaminic–anticholinergic
agents given one to several times each day may
be effective, especially when the first dose is
administered prior to motion.
 TREATMENT
Pharmacologic
DISORDERS OF BALANCE
• Scopolamine is commonly used to prevent
nausea or vomiting caused by motion.
• Transdermal system (patch) increased patient
satisfaction and decreased untoward side effects
• A review of 12 randomized, controlled studies
showed that scopolamine provided better
protection from motion-induced sickness than
did placebo, but was not superior to
antihistamines and combinations of scopolamine
and ephedrine.
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• 75% of pregnant women during the first
trimester of pregnancy.
• The severity of the symptoms varies
considerably, from mild nausea to
incapacitating nausea and vomiting.
• The etiology is not well understood.
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• For the majority of women, these symptoms are
self-limited, although approximately 1% to 3%
develop hyperemesis gravidarum, a serious
condition marked by severe physical symptoms
and/or medical complications requiring
hospitalization.
• In its most severe state, hyperemesis gravidarum
may result in volume contraction, starvation, and
electrolyte abnormalities.
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• Initial management of NVP often involves
dietary changes and/or lifestyle modifications.
• Nonpharmacologic: ginger and acupressure
(lacking efficacy trials)
• Persistent nausea and/or vomiting leads to the
consideration of drug therapy at a time when
teratogenic potential of each agent must be
considered.
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• Pyridoxine (Vit B6) (10 to 25 mg 1 to 4 times daily),
with or without doxylamine (12.5 to 20 mg 1 to 4 times
daily), is recommended as first-line therapy.
• If symptoms persist, addition of an histamine1-
receptor antagonist such as dimenhydrinate (50 to 100
mg orally or rectally every 4 to 6 hours as needed),
diphenhydramine (25 to 50 mg orally or 10 to 50 mg
intravenously [IV] every 4 to 6 hours as needed), or
meclizine (25 mg orally every 4 to 6 hours as needed) is
recommended.
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• Dopamine antagonists can also be added if
symptoms continue (metoclopramide 5 to 10
mg IV every 8 hours as needed; promethazine
12.5 to 25 mg IV every 4 hours as needed;
prochlorperazine 5 to 10 mg orally every 6
hours as needed).
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• Patients with persistent NVP or who show signs
of dehydration should receive intravenous fluid
replacement with thiamine (Vit B1).
• Ondansetron 2 to 8 mg orally/IV every 8 hours as
needed may alleviate NVP, but the only
randomized, controlled trial of intravenous
ondansetron showed it to be no more effective
than promethazine for treatment of severe NVP.
 TREATMENT
Pharmacologic
ANTIEMETIC USE DURING PREGNANCY (NVP)
• Corticosteroids should be reserved for
patients with refractory NVP or hyperemesis
gravidarum; methylprednisolone 16 mg
orally/IV every 8 hours for 3 days followed by
a 2-week taper is recommended.
• This regimen may be repeated if necessary,
but treatment should not exceed a total of 6
weeks.
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
 TREATMENT
Pharmacologic
ANTIEMETIC USE IN CHILDREN
• Practice guidelines recommend that a corticosteroid
plus SSRI should be administered to children receiving
chemotherapy of high or moderate emetic risk.
• The best doses or dosing strategies for children (by age,
weight, or body surface area) have not been clearly
established.
• Standard adult doses of SSRIs may not provide
consistent antiemetic protection in children due to
wider interpatient variations in metabolism and
clearance.
 TREATMENT
Pharmacologic
ANTIEMETIC USE IN CHILDREN
• For nausea and vomiting associated with
pediatric gastroenteritis, emphasis should be
placed on rehydration measures rather than on
pharmacologic intervention.
• Promethazine suppositories were the most
commonly prescribed antiemetic for pediatric
gastroenteritis in a survey of physicians, despite
the lack of prospective trials for this agent.
 TREATMENT
Pharmacologic
ANTIEMETIC USE IN CHILDREN
• In 2004, the Food and Drug Administration reviewed all
cases (125) of serious adverse events that involved children
(age range: birth to 16 years) who had received any
formulation of promethazine.
• Serious outcomes, including death, occurred with all routes
of administration (oral, rectal, and parenteral) at doses
ranging from 0.45 to 6.4 mg/kg.
• Subsequently, a black box warning was added to the
promethazine labeling that included a contraindication for
use of any product containing promethazine in children
younger than age 2 years and a strengthened warning with
regard to use in children 2 years of age or older.
 TREATMENT
Pharmacoeconomic Considerations
• Many important variables to consider
• Medication costs alone cannot begin to explain
the true pharmacoeconomic outcome associated
with the use of antiemetic drugs.
• For example, the costs associated with an
unexpected hospital admission because of
vomiting after an outpatient surgical procedure
quickly offset the savings related to the selection
of an inexpensive antiemetic drug.
 TREATMENT
Pharmacoeconomic Considerations
• In this and other similar situations, it is economically and
clinically important to develop antiemetic protocols based
on appropriate decision analysis and clinical outcomes in
order to optimize drug product selection.
• The clinical practice guidelines that have been previously
described are valuable tools when developing institution-
specific antiemetic protocols.
• The availability of new, more expensive agents will only
increase the costs associated with the prophylaxis of CINV
and PONV.
• The need to control antiemetic costs for health systems is
universal and formulary management strategies have been
described.
 TREATMENT
Evaluation of Therapeutic Outcomes
• In accordance with the information presented
concerning age and clinical condition, individualized
therapy is possible through drug selection and dosage
adjustment.
• Monitoring criteria for drug therapy should include the
subjective assessment of the patient’s severity of
nausea, as well as objective parameters, such as
changes in patient weight, the number of vomiting
episodes each day, the volume of vomitus lost, and
evaluation of fluid, acid–base balance, and electrolyte
status, with particular attention to serum sodium,
potassium, and chloride concentrations.
 TREATMENT
Evaluation of Therapeutic Outcomes
• In addition, evaluation of renal function may
become important, particularly in patients with
volume contraction and progressive electrolyte
disturbances.
• Specific parameters include daily urine volume,
urine specific gravity, and urine electrolyte
concentrations.
• Physical assessment of patients should include
evaluation of mucous membranes and skin
turgor, because dryness of these tissues may be
indicative of significant volume loss.
Thank You