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Introduction

Nausea is an uneasy or unsettled feeling in the stomach together with an urge to vomit. Nausea and vomiting, or throwing up, are not diseases. They can be symptoms of many different conditions. These include :
morning sickness during pregnancy, infections,

migraine headaches,
motion sickness, food poisoning, cancer chemotherapy or other medicines. others

Introduction
Nausea and vomiting are common. Usually, they are not serious. BUT IF the following cases occur immediate referral is recommended
Vomited for longer than 24 hours

Blood in the vomit


Severe abdominal pain Headache and stiff neck

Pathophysiology
Nausea and vomiting consist of three stages:
1. Nausea, : nausea is the subjective feeling of a need to vomit. It is often accompanied by autonomic symptoms such as pallor, tachycardia, diaphoresis, and salivation 2. Retching, which follows nausea, consists of diaphragm, abdominal wall, and chest wall contractions and spasmodic breathing against a closed glottis. Retching can occur without vomiting, but this stage produces the pressure gradient needed for vomiting, although no gastric contents are expelled. 3. Vomiting, or emesis, is a reflexive, rapid, and forceful oral expulsion of upper gastrointestinal contents due to powerful and sustained contractions in the abdominal and thoracic musculature.1 Vomiting, like nausea, can be accompanied by autonomic symptoms. note : Regurgitation, unlike vomiting, is a passive process without involvement of the abdominal wall and diaphragm wherein gastric or esophageal contents move into the mouth. in patients with gastro esophageal reflux disease (GERD), one hallmark symptom is acid regurgitation.

Pathophysiology
Various areas in the brain and the gastrointestinal (GI) tract are stimulated when the body is exposed to noxious stimuli (e.g., toxins), gastro-intestinal irritants (e.g., infectious agents), or chemotherapy. These areas include :
the chemoreceptor trigger zone (CTZ) in the area postrema of the fourth ventricle of the brain,(outside BBB-???) serotonin type 3

(5-HT3), neurokinin-1 (NK1), and dopamine (D2) receptors.

the vestibular system (H1,M) visceral afferents from the GI tract (5-HT3 R ), the cerebral cortex.

Chemoreceptor trigger zone (CTZ) (5-ht3, D2, NK!)

CTH, TOXINS

Vestibular system (H1, Muscarinic)

Motion,
Cerebral cortex (sensory input ) Emotional causes Gastrointestinal visceral afferents (5ht3, D2, NK1)

Central vomiting centers (medulla)

Stimulation of salivation & respiratory centers, pharyngeal , GI, Abdominal muscle contraction

Nausea & vomiting

CTH, INFECTIONS

Physiologic pathways that result in nausea and vomiting. 5-HT3, serotonin type 3 receptor; D2, dopamine histamine type 1 receptor, NK1, neurokinin-1. 6(Adapted type 2 receptor; GI, gastrointestinal; H1, Pharmacists. ASHP therapeutic guidelines on the from American Society of Health-System pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery

Pathophysiology
Motion sickness is caused by stimulation of the vestibular system. This area contains many histaminic (H1) and muscarinic cholinergic receptors. The higher brain (i.e., cerebral cortex) is affected by sensory input such as sights, smells, or emotions that can lead to vomiting. This area is involved in anticipatory nausea and vomiting associated with chemotherapy. Nausea and vomiting can be classified as either simple or complex.
Simple nausea and vomiting occurs occasionally and is either selflimiting or relieved by minimal therapy. It does not have detrimental effects on hydration status, electrolyte balance, or weight because it is short-lived.

complex nausea and vomiting requires more aggressive therapy because electrolyte imbalances, dehydration, and weight loss may occur. Unlike simple nausea and vomiting, complex nausea and vomiting can be caused by exposure to noxious agents.

Neuroanatomical Centers: Emetic center Chemoreceptor trigger zone Vagal afferents of GI


Neurotransmitters: Dopamine (DA) Serotonin (5HT) Substance P GABA Cannabinoid I Acetylcholine Endorphins
Emetic Center

CTZ

Rubenstein ED, et al Cancer J 2006

Assessment & Interpretation


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Nature & severity


Projectile vomiting :
babies pyloric stenosis , Adults with history of peptic ulceration (usually duodenal ).

Sour smelling vomit possible obstruction (e.g. pyloric stenosis) Blood stained vomit (hematemesis)
Blood may appear:
fresh & bright red, or dark with clotted appearance If blood originates in the stomach , it will be degraded by gastric acid producing a dark colored vomit with a coffee ground appearance

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Onset & duration


Frequent vomiting for more than 2448hr. Deteriorating nausea , increased incidence of vomiting over a longer period of time

Sudden vomiting without nausea is a characteristic of a central cause (e.g. Cerebral tumor or injury), Nausea preceding vomiting indicates a gastrointestinal cause.

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Accompanying symptoms
Abdominal pain may cause reflex vomiting as in:
liver disease renal colic appendicitis , hernias & biliary colic genital disorder

paroxysmal coughing can lead to vomiting .

Other disorders may lead to vomiting include Mnires disease & acute pain in extra abdominal body system (glaucoma)
Gastroenteritis : Diarrhea accompanying vomiting suggests , usually due to ingestion of some dietary insult or to infection or food food poisoning : Recent travelers to hot countries should be referred to eliminate dysentery &

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Accompanying symptoms
Central nervous disorder (e.g. space occupying lesions, meningitis , head injury & subdural hemorrhage )

Migraine attacks.
Anxiety or an emotional disturbance anorexia nervosa & bulimia. Note: Episodic or chronic vomiting accompanied by weight loss requires referral for investigation of the cause .

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Causative & modifying factors


If the cause can be elicited, the decision of whether to refer or not becomes easier Common dietary cause are hot or spicy foods , over indulgence of food or alcohol , & sensitivity to certain foods (e.g.. Sea food , pork). such case will usually resolve spontaneous within 24 hrs. Many drugs can cause nausea & vomiting (e.g. NSAIDS, colchicine , digoxin in toxic doses, Fe , levodopa , theophylline , estrogens & cytotoxic drugs ) Motion is a common cause of N&V, & in severe cases may persist for a day or 2 after the journey Infection may cause vomiting , especially otitis media in children & the early stages of various viral illness(measles). Condition affecting the abdomen may result in reflex vomiting. Heart failure , particularly right sided HF may result in congestion of the abdominal organs with blood , giving a sensation of nausea & sometimes vomiting.

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Causative & modifying factors


Episodes of vomiting which may sometimes be severe, in patients with diabetes , require immediate referral to exclude loss of control of the diabetes. Chronic alcoholic patients may suffer from early morning vomiting

2 types of vomiting may occur in pregnancy :


The familiar syndrome of morning sickness comprises regular bouts of short lived N or V or both during the 1st few weeks of pregnancy. it may occur at any time of the day . It usually resolve spontaneously around the 3rd month of pregnancy . Drugs should not be recommended but reassurance , frequent small meals , rest , and bed rest in the morning are sensible recommendation . A more sever form of vomiting which may occur in early pregnancy Is hyperemesis gravidarum , it may lead to dehydration & shock & requires medical referral

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Risk factors in children


Vomiting in children is usually self remitting but certain points should be remembered Many babies regurgitate their milk after meal (posseting) & mothers should be assured that this is normal However , in cases of projectile vomiting (baby may be alert & appear normal OR in babies who appear distressed, irritable or very drowsy)referral is required Children over 2 years of age require referral if they have vomited for more than 24hrs

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Management
If the cause of vomiting has been identified or is suspected, the underlying disorder should be attended to as a priority Management :
Non pharmacologic Pharmacologic

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Non pharmacologic management


General Measures:
resting the stomach avoid strong perfumes evaporation of mint may be helpful sit in an upright position for 30 - 45 minutes after eating Avoiding drinking milk or eating heavy or fatty warm, very spicy and odorous meals for 24 hrs.

Sips of tasteless drinks, ideally water, should be taken regularly to prevent dehydration
Food should be avoided until the patients feels hungry (start with bread toast or plain biscuits ) If tolerated , intake may be increased carefully till a normal diet is tolerated

Administration of fluids and electrolytes

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Non pharmacologic management


Acupuncture and acupressure There are indications that acupuncture and/or acupressure (in the form of pressure massage or a special wristband) are effective in the case of nausea and vomiting, particularly after surgery and after chemotherapy. Complementary therapies and psychological techniques for psychogenic factors (anxiety and stress) and conditioning (anticipatory nausea and vomiting) play an important role. These types of nausea and vomiting respond poorly to antiemetics. These techniques act through relaxation, distraction, and/or a feeling of self-control.
P6 (Neiguan) point

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Pharmacologic drug treatment


There are few oral drugs available to treat vomiting attacks

Both antihistamines & anti muscarinic drugs may be useful to prevent attacks , especially of motion sickness.
Anti histamine such as cinnarizine , diphenhydramine & promethazine which also possess anticholinergic properties , may be useful , but should be used in caution in patients with glaucoma , prostatitis , constipation & those who drive. Note:
Babies and young children should be given oral rehydration fluid that replace glucose , Na , K lost during vomiting . Glucose enhance the absorption of electrolytes across the inflamed mucosa .

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The use of proprietary rehydration fluids in children should be encourage over home remedies to prevent inappropriate load of Na , & K

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Drug Class Information


Antacids
magnesium hydroxide, aluminum hydroxide, and/or calcium carbonate, relieve N&V, (through gastric acid neutralization.)

Histamine-2 Receptor Antagonists


cimetidine, famotidine, nizatidine, ranitidine heartburn or GERD . N&V associated with

AntihistamineAnticholinergic Drugs
treatment of simple symptomatology. Adverse reactions that may be apparent with the use of the antihistaminic anticholinergic agents primarily include drowsiness or confusion, blurred vision, dry mouth, urinary retention, and possibly tachycardia, particularly in elderly patients.

Phenothiazines chlorpromazine , promethazine


Phenothiazine are most useful in patients with simple nausea and vomiting.

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dangerous side effects, including extrapyramidal reactions, hypersensitivity reactions with possible liver dysfunction, marrow aplasia, and excessive sedation.

Metoclopramide
Metoclopramide increases lower esophageal sphincter tone, aids gastric emptying, and accelerates transit through the small bowel, possibly through the release of acetylcholine. Metoclopramide is used for its antiemetic properties in patients with diabetic gastroparesis and with dexamethasone for prophylaxis of delayed nausea and vomiting associated with chemotherapy administration.

Corticosteroids
Dexamethasone has been used successfully in the management of chemotherapy- induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV), either as a single agent or in combination with selective serotonin reuptake inhibitors (SSRIs). For CINV, dexamethasone is effective in the prevention of both Cisplatin-induced acute emesis and when used alone or in combination for the prevention of delayed nausea and vomiting associated with CINV.

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Selective Serotonin Receptor Inhibitors (Ondansetron, Granisetron, Dolasetron, and Palonosetron)


SSRIs (dolasetron, granisetron, ondansetron, and palonosetron) act by blocking presynaptic serotonin receptors on sensory vagal fibers in the gut wall. The most common side effects associated with these agents are constipation, headache, and asthenia

Cannabinoids
When compared with conventional antiemetics, oral nabilone and oral dronabinol were slightly more effective than active comparators in patients receiving moderately emetogenic chemotherapy regimens. The efficacy of cannabinoids as compared to SSRIs for CINV has not been studied. They should be considered for the treatment of refractory nausea and vomiting in patients receiving chemotherapy.

Substance P/Neurokinin 1 Receptor Antagonists


Substance P is a peptide neurotransmitter in the NK family whose preferred receptor is the NK1 receptor. Substance P is believed to be the primary mediator of the delayed phase of CINV and one of two mediators of the acute phase of CINV. Aprepitant is the first approved member of this class of drugs and is indicated as part of a multiple drug regimen for prophylaxis of nausea and vomiting associated with high-dose cisplatin-based chemotherapy.

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Numerous potential drug interactions are possible; clinically significant drug interactions with oral contraceptives, warfarin, and oral dexamethasone have been described.