US Pharm. 2013;38(12):24-28.
and vomiting (N/V) is a common complaint among patients across all ages
and levels of care. Symptoms of N/V may be self-treated or require
referral to another provider for further work-up of possible causes.
Selection of appropriate prevention and treatment is reliant upon
understanding the precipitating physiological mechanisms from which N/V
results. N/V may be caused by the vestibular system, stimulation of
receptors at the chemoreceptor trigger zone, or infectious origins.
Disease states may exacerbate symptoms or cause secondary N/V. The
pharmacist plays an important role in the management of N/V including
proper referral, medication selection, review of drug interactions or
causes, and patient counseling.
Nausea and vomiting (N/V) is a common complaint among patients across all ages and levels of care. Nausea is defined as the feeling of a need to vomit and vomiting as the expulsion of gastric contents via abdominal and chest wall contractions.1
The clinical presentation of N/V may involve the symptoms described
above as well as signs of dehydration and electrolyte imbalance such as
hypokalemia or metabolic acidosis. A thorough patient history for onset,
timing of symptoms, nature of vomitus, and other signs that referral is
appropriate is necessary to accurately assess the correct treatment
option.1,2 The pharmacist should be able to assess medication
efficacy for preventing and treating N/V to help establish a firm
recommendation to the patient or provider.
Various receptors are involved in the process of N/V,
which stimulate the central vomiting center (CVC) in the medulla to
initiate the physiological process of N/V. The chemoreceptor trigger
zone (CTZ) responds to noxious stimuli, gastrointestinal (GI) irritants,
or chemotherapy. Located outside the blood-brain barrier, the CTZ is
sensitive to systemic toxins, acidosis, and uremia. Dopamine-2 (D2),
serotonin (5HT3), and neruokinin-1 (NK1) receptors are located in the
CTZ and are mediated by GI distention, infection, and mucosal
irritation. The vestibular system, as it pertains to N/V, is stimulated
by the action of histamine1 (H1) and muscarinic (M1)
receptors. Sensory input to the cerebral cortex is responsible for
activation of the CVC and subsequent N/V. N/V is best differentiated
based on the type of receptor influencing the reaction, and selection of
the best treatment is dependent upon the mediating receptor and
Causes of N/V
Medications: N/V is a
common side effect of medications to varying degrees of clinical
relevance. Most instances of drug-induced N/V are from activation of D2,
5HT3, H1, and M1 receptors and are dependent on the specific medication
utilized. Some drugs, such as metformin, may cause N/V when
administered without food; simply administering with food would save a
beneficial drug from being discontinued due to unpleasant side effects.
Classes of medications commonly associated with N/V include opiates,
digoxin, dopamine agonists, hormones, and nicotine.1
medications used for cancer chemotherapy are especially tied to N/V,
which is classified as postchemotherapy nausea and vomiting (PCNV) or
chemotherapy-induced N/V (CINV). PCNV is further subdivided into the
acute phase, which is N/V within 24 hours of chemotherapy; the delayed
phase, which occurs after 24 hours postadministration of chemotherapy;
and the anticipatory phase, brought about by the anticipation of
chemotherapy administration. The treatment of PCNV varies on the
emetogenicity of the chemotherapy agent used and usually necessitates
more than one class of antiemetic.1
Disease States: Diseases
that may induce N/V include gastroparesis, cyclic vomiting, migraine,
gastric outlet obstruction, and peptic ulcer disease. Gastroparesis may
be medication-induced or caused by physiological changes such as those
found in patients with long-standing diabetes mellitus who rely on
insulin for glucose control.5 Drugs that are found to induce
gastroparesis include narcotics, clonidine, dopamine agonists, tricyclic
antidepressants, calcium channel blockers, lithium, and progesterone.1
Infectious causes of N/V are typically acute in onset and self-limiting.
Viral gastroenteritis and bacterial sources may be responsible. For
example, food poisoning from staphylococcal enterotoxin will typically
present within 6 hours of ingestion, with symptoms lasting up to 48
nausea and vomiting (PONV) may be experienced from inpatient or
outpatient procedures. The overall incidence of N/V from outpatient
procedures postdischarge has been estimated at 17% for nausea and 8% for
vomiting.7 Symptoms may present and last up to 3 days after
the procedure, making it difficult for providers to evaluate the patient
for appropriate treatment in out-patient procedures. Pain, hypotension,
dehydration, and anesthesia have been identified as risk factors for
PONV, with treatment depending on the individual patient and on
maximizing antiemetic therapy with multiple medications.7
N/V related to motion sickness and vertigo is due to stimulation of the
vomiting center located in the vestibular system. Sensory nerves
located here contain H1 and M1 receptors.3
Pregnancy: Pregnancy is frequently associated with N/V and is commonly referred to as morning sickness. The incidence of pregnancy-induced N/V is high, with up to 70% of women reporting N/V in the first trimester.1 One mechanism behind N/V in pregnancy is human chorionic gonadotropin (hCG) stimulation of the CTZ.4
Women often experience most N/V in the first trimester when hCG levels
are highest, though it can occur at any point throughout the pregnancy.4,8 Other factors contributing to N/V in pregnancy include elevated estrogen levels, gastric reflux, and hyperthyroidism.4
Acupressure Wristbands: Devices
such as the Sea-Band function by stimulating the pericardium 6 (P6)
point on the forearm. They can be useful in preventing N/V in a variety
of conditions, such as pregnancy or motion sickness, where traditional
drug therapy may not be warranted or desired.2
Vitamins/Herbals: A variety of botanical products have been advocated for use in N/V. Ginger (Zingiber officinale) has some limited data to support use in pregnancy, motion sickness, and surgery.2 Ginger does not produce central nervous system (CNS) depression, and may be an alternative to antihistamines. Peppermint (Mentha piperita), chamomile (Matricaria recutita), and lemon balm (Melissa officinalis) are thought to have antispasmodic properties that may be helpful in treating N/V.2,6 Vitamin B6
(pyridoxine) has also been advocated for use in pregnant women
experiencing N/V and is included in the recently approved product
Often pharmacologic means are necessary to prevent or
treat N/V. Effective regimens are varied and carry unique considerations
as to use in certain disease states, drug interactions, and adverse
effects. Antiemetics are listed in TABLES 1 and 2.1,10-16
agents exhibit their antiemetic effect as a result of their
antimuscarinic properties. Most of their efficacy is seen with the
prevention of N/V, especially from vestibular causes such as motion
sickness.1 Ideally, patients should be instructed to take the
antihistamine 30 to 60 minutes before they expect to experience the
stimulating event.2 The main side effects of antihistamines are anticholinergic, notably varying degrees of drowsiness.1
Worsening urinary retention should be considered in those predisposed
to this effect because of conditions such as benign prostatic
hyperplasia.1,2 The combination product Diclegis (doxylamine-pyridoxine) contains an antihistamine along with vitamin B6. It is Pregnancy Category A and is useful in N/V of pregnancy.10
drugs work centrally at dopamine receptors in the CTZ and are available
in a variety of dosage forms. They are useful for treating
moderate-to-severe episodes of N/V related to motion sickness, PONV, and
migraine. Adverse effects of this drug class include sedation,
orthostasis, and extrapyramidal effects. Rare cases of neuroleptic
malignant syndrome have been reported.1
agents are useful for PONV and anticipatory N/V caused by chemotherapy.
Butyrophenones, such as haloperidol, have mechanisms and adverse-effect
profiles similar to phenothiazines.1
5HT3 Antagonists: These drugs antagonize
serotonin receptors both peripherally and centrally in the CTZ. In the
periphery, 5HT3 receptors trigger vagal stimulation of the medulla,
causing N/V.1 The selective blockade of both peripheral and
central inhibition of 5HT3 receptors makes these agents a useful
antiemetic for many forms of N/V.7 5HT3 antagonists are generally well tolerated and have become a staple for treatment of PCNV and CINV.1
such as the benzamides antagonize dopamine receptors centrally, with
effects both centrally and peripherally. Their prokinetic effects are
useful for a variety of clinical N/V scenarios, especially those needing
an increase in gastric motility, such as gastroparesis.12,15
Metoclopramide is primarily used in the United States because
domperidone is only available as a compounded agent under an
Investigational New Drug Application.11 Domperidone poorly
penetrates the blood-brain barrier, and thus results in fewer central
side effects such as tardive dyskinesias and extrapyramidal effects.
Metoclopramide, due to its centrally mediated dopamine antagonism of
receptors, has a significant adverse-effect profile that includes
dystonia, dyskinesia, akathisia, and hyperprolactinemia, a potential
cause of gynecomastia and lactation. The overall incidence of adverse
effects is estimated at 10% to 20% with metoclopramide versus 5% to 10%
Phosphorated Carbohydrate Solution: This
mixture of fructose (1.87 g/5 mL), glucose (1.87 g/5 mL), and
phosphoric acid (21.5 g/5 mL) is available OTC for N/V (Emetrol). Its
mechanism may be related to delay of gastric emptying time and decreased
smooth-muscle contraction. Because of its high carbohydrate content,
this product is not recommended for patients with diabetes mellitus.2,16
When to Refer a Patient
Patients should be referred when presenting with severe or
alarm symptoms such as signs of dehydration, fever, bloody vomitus,
jaundice, changes in vision, severe headache, or neck pain. If a
patient’s medical history includes asthma, chronic bronchitis, or
emphysema, the patient may react adversely to OTC treatments and should
be referred. If a pharmacist suspects that a patient’s N/V is related to
anorexia or bulimia, he or she should ensure that the patient receives
appropriate counseling by a trained professional. If poisoning is
suspected, the pharmacist should call the Poison Control Help Line at
Another patient presentation that requires referral is N/V due to a chronic condition, such as gastroparesis and
or prolonged N/V. Symptoms persisting longer than 1 week after an
appropriate intervention is made could indicate a more serious etiology
and should be referred.2
QT Prolongation Concerns
Prolongation of the QT may be a result of a medication’s
mechanism of action, drug interactions, alteration of metabolism or
elimination, or augmentation of concomitant QT prolongation effects from
other agents. Many commonly prescribed antiemetics carry specific
warnings regarding QT prolongation. For example, the FDA recently placed
a warning for QT prolongation with ondansetron. Ondansetron’s QT
prolongation is exhibited in a dose-dependent manner; hence, the FDA has
advised to cease using the 32-mg single IV dosage.17
Domperidone may also significantly prolong the QT interval. For this
reason, a baseline ECG is recommended with a corrected QT interval
assessed prior to starting therapy.15,18,19
The manner in which pharmacists handle general QT
prolongation warnings is dependent on the tools available to them. Most
outpatient pharmacies will not have a patient laboratory or ECG
capability, but should have the patient’s medication record. Watching
for high-risk drug-drug and drug-disease state interactions, as well as
educating patients on the risks of torsade de pointes, is necessary.
Targeting patients with heart disease and individuals on medications
that can increase the risk of potassium and magnesium abnormalities
should help the pharmacist identify the appropriate counseling.18
N/V is a complex condition that presents with a great
variety of disease states, medications, and other causes. Proper
outpatient therapy is reliant on identifying the causative factors
behind a patient’s N/V, knowing when referral is warranted, and
selecting the appropriate treatment.
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2. Berardi RR, Ferrari SP, Hume AL, et al. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. 16th ed. Washington, DC: American Pharmacists Association; 2009.
3. Hoffman R, Benz EJ Jr, Silberstein LE, et al. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA: Saunders; 2012.
4. Casey G. Treating nausea and vomiting. Nurs N Z. 2012;18:20-24.
5. Choung RS, Locke GR III, Schleck CD, et al. Risk of
gastroparesis in subjects with type 1 and 2 diabetes in the general
population. Am J Gastroenterol. 2012;107:82-88.
6. Scorza K, Williams A, Phillips JD, Shaw J. Evaluation of nausea and vomiting. Am Fam Physician. 2007;76:76-84.
7. Cruthirds D, Sims PJ, Louis PJ. Review and
recommendations for the prevention, management, and treatment of
postoperative and postdischarge nausea and vomiting. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:601-611.
8. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. 2010;363:1544-1550.
9. Ashkenazi-Hoffnung L, Merlob P, Stahl B, Klinger G.
Evaluation of the efficacy and safety of bi-daily combination therapy
with pyridoxine and doxylamine for nausea and vomiting of pregnancy. Isr Med Assoc J. 2013;15:23-26.
10. Diclegis (doxylamine succinate and pyridoxine hydrochloride) package insert. Bryn Mawr, PA: Duchesnay USA, Inc; 2013.
11. Micromedex Healthcare Series [Internet database]. www.micromedex.com. Greenwood Village, CO: Truven Health Analytics. Accessed August 28, 2013.
12. Facts & Comparisons 4.0. St. Louis, MO: Wolters Kluwer Health Inc. www.factsandcomparisons.com. Accessed August 28, 2013.
13. Zofran (ondansetron) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2004.
14. Aloxi (palonosetron) package insert. Woodcliff Lake, NJ: OSO Biopharmaceuticals, LLC; 2013.
15. Camilleri M, Parkman HP, Shafi MA, et al; American
College of Gastroenterology. Clinical guideline: management of
gastroparesis. Am J Gastroenterol. 2013;108:18-37.
16. Emetrol Cherry (phosphorated carbohydrate solution) package insert. Sarasota, FL: Preferred Pharmaceuticals, Inc; 2012.
17. Ondansetron (Zofran) 32 mg, single IV dose: updated
safety communication—product removal due to potential for serious
cardiac risks. FDA. December 4, 2012.
Accessed August 29, 2013.
18. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013-1022.
19. Kallergis EM, Goudis CA, Simantirakis EN, et al.
Mechanisms, risk factors, and management of acquired long QT syndrome: a
comprehensive review. ScientificWorldJournal. 2012;2012:212178.
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