What is the treatment approach for nausea and vomiting, including considerations for special populations such as pregnant women, children, and the elderly, and what medications should be avoided in these groups?

Treatment of Nausea and Vomiting

General Approach for Adults

For acute nausea and vomiting in adults without alarm symptoms, start with dopamine receptor antagonists (prochlorperazine, haloperidol, or metoclopramide) as first-line therapy, titrated to maximum benefit and tolerance. 1

Stepwise Treatment Algorithm

• First-line: Dopamine receptor antagonists (metoclopramide 10 mg three times daily before meals, prochlorperazine, or haloperidol) should be initiated and titrated to effect 1

• Second-line: If vomiting persists after first-line therapy, add a 5-HT3 receptor antagonist (ondansetron 8 mg orally 2-3 times daily or 0.15 mg/kg IV over 15 minutes, maximum 16 mg per dose) 1

• Third-line: For refractory symptoms, add one or more of the following: anticholinergic agents, antihistamines, or cannabinoids 1

• Fourth-line: For severe refractory cases, consider adding corticosteroids, continuous intravenous or subcutaneous infusion of antiemetics, or olanzapine 1

The key principle is adding agents from different drug classes rather than replacing one antiemetic with another, as different neuroreceptors are involved in the emetic response 1

Route of Administration Considerations

• Oral routes are often not feasible during active vomiting; rectal or intravenous therapy is frequently required 1
• Alternative formulations include ondansetron sublingual tablets, promethazine or prochlorperazine rectal suppositories, and alprazolam sublingual or rectal forms 1

Supportive Care

• Ensure adequate hydration and fluid repletion in all patients with persistent vomiting 1
• Assess and correct electrolyte abnormalities, particularly hypokalemia 2

---

Pregnancy-Related Nausea and Vomiting

Early treatment of nausea and vomiting in pregnancy may reduce progression to hyperemesis gravidarum; begin with vitamin B6 and doxylamine as first-line therapy, then escalate systematically. 3

Stepwise Treatment for Pregnancy

• First-line: Vitamin B6 (pyridoxine) combined with doxylamine, along with dietary modifications (small, frequent meals) 3

• Second-line: For moderate symptoms, add ondansetron, metoclopramide, or promethazine 3

• Third-line: For severe cases or hyperemesis gravidarum, use intravenous hydration and consider intravenous glucocorticoids 3

Medications to AVOID in Pregnancy

• Methotrexate is absolutely contraindicated at any stage of pregnancy due to severe teratogenic effects 3
• Older-generation alkylating agents (procarbazine, busulfan), thalidomide, lenalidomide, pomalidomide, and tretinoin are contraindicated 3
• Chemotherapy should be avoided during the first trimester due to greater risk of teratogenic effects, including major congenital malformations, spontaneous abortions, and fetal death 3

Safety Profile in Pregnancy

• Ondansetron, metoclopramide, and promethazine have been used in pregnant women without significant side effects when used in the second and third trimesters 3
• Granulocyte-colony stimulating factors and antiemetics for treatment-related side effects can be integrated into supportive care during pregnancy 3

---

Pediatric Considerations

For children over 4 years of age with acute gastroenteritis and vomiting, ondansetron may be given to facilitate tolerance of oral rehydration. 3

Key Pediatric Guidelines

• Antimotility drugs (loperamide) should not be given to children under 18 years of age with acute diarrhea 3
• Reduced osmolarity oral rehydration solution (ORS) is first-line therapy for mild to moderate dehydration in children with acute diarrhea and vomiting 3
• Human milk feeding should be continued throughout the diarrheal episode in infants 3
• Oral zinc supplementation reduces duration of diarrhea in children 6 months to 5 years of age in areas with high prevalence of zinc deficiency 3

---

Elderly Population

In elderly patients, assess for volume depletion using the seven-sign assessment (confusion, non-fluent speech, extremity weakness, dry mucous membranes, dry tongue, furrowed tongue, sunken eyes) before initiating antiemetic therapy. 2

Critical Assessment in Elderly

• The presence of four or more of these clinical signs indicates moderate to severe volume depletion requiring urgent fluid resuscitation 2
• Postural pulse change ≥30 beats per minute from lying to standing indicates blood loss of at least 630 mL (sensitivity 97%, specificity 98%) 2
• Elderly patients may not mount typical tachycardic responses to hypovolemia due to beta-blockers or autonomic dysfunction 2

Medications to AVOID in Elderly

• Elderly patients are particularly sensitive to benzodiazepines and anticholinergic medications, which worsen confusion and increase fall risk 2
• Review the Beers Criteria to identify potentially inappropriate medications that may contribute to nausea and vomiting 2
• Daily dosage of amantadine should not exceed 100 mg in elderly patients due to declining renal function and increased central nervous system side effects 3

Metabolic Causes to Evaluate

• Hypokalemia and uremia (renal failure) can directly trigger nausea and vomiting in elderly patients 2
• Order comprehensive metabolic panel (electrolytes, renal function, glucose, calcium) to evaluate for metabolic derangements 2

---

Chemotherapy-Induced Nausea and Vomiting

For patients receiving high-emetic-risk chemotherapy (cisplatin or anthracycline plus cyclophosphamide), use a four-drug combination: NK1 receptor antagonist, 5-HT3 receptor antagonist, dexamethasone, and olanzapine. 3

High-Emetic-Risk Regimens

• For cisplatin and other high-emetic-risk agents: NK1 receptor antagonist + 5-HT3 receptor antagonist + dexamethasone + olanzapine on day 1, with dexamethasone and olanzapine continued on days 2-4 3
• For anthracycline combined with cyclophosphamide: same four-drug combination, but dexamethasone only on day 1, with olanzapine continued on days 2-4 3

Moderate-Emetic-Risk Regimens

• For carboplatin AUC ≥4 mg/mL per minute: three-drug combination of NK1 receptor antagonist + 5-HT3 receptor antagonist + dexamethasone 3
• For other moderate-emetic-risk agents: two-drug combination of 5-HT3 receptor antagonist (day 1) + dexamethasone (day 1) 3

---

Critical Warnings and Contraindications

When NOT to Use Antiemetics

• Do not use antiemetics in suspected mechanical bowel obstruction without surgical consultation, as this can mask progression and delay necessary intervention 2, 1
• Antimotility drugs should be avoided in inflammatory diarrhea or diarrhea with fever due to risk of toxic megacolon 3

Medication-Specific Warnings

• Metoclopramide carries a black box warning for tardive dyskinesia, though risk may be lower than previously estimated 1
• Ondansetron can cause QT prolongation; monitor in patients with cardiac risk factors 4
• Monitor for extrapyramidal side effects with dopamine receptor antagonists 1

Special Clinical Situations

• For anxiety-related nausea, add benzodiazepines (lorazepam), but avoid long-term use due to dependence risk 1
• For gastritis or gastroesophageal reflux contributing to vomiting, use proton pump inhibitors or H2 receptor antagonists 1
• Zanamivir is not recommended for patients with underlying airway disease due to risk of serious adverse events 3