Antiemetic Drugs

Adverse Effects of Antiemetics

Anticholinergics Dizziness, drowsiness, disorientation, tachycardia Blurred vision, dilated pupils, dry mouth Urinary retention, constipation Rash, erythema Antihistamines Dizziness, drowsiness, confusion Blurred vision, dilated pupils, dry mouth Urinary retention Dopamine Antagonists Orthostatic hypotension, tachycardia Extrapyramidal symptoms, tardive dyskinesia Headache Blurred vision, dry eyes Urinary retention Dry mouth, nausea and vomiting, anorexia Constipation Serotonin Antagonists Headache Diarrhea, rash, bronchospasm, prolonged QT interval Cannabinoids Drowsiness, dizziness, anxiety, confusion, euphoria, visual disturbances, dry mouth Glucocorticoids Dexamethasone Long-term therapy: Muscle wasting (esp. arms, legs), osteoporosis, spontaneous fractures, amenorrhea, cataracts, glaucoma, peptic ulcer disease, HF Ophthalmic: Glaucoma, ocular hypertension, cataracts Abrupt withdrawal following long-term therapy: Severe joint pain, severe headache, anorexia, nausea, fever, rebound inflammation, fatigue, weakness, lethargy, dizziness, orthostatic hypotension

Drug Interactions of Antiemetics

Anticholinergics with Antihistamines and Antidepressants When anticholinergics are used with antihistamines and antidepressants, an additive drying effect occurs. Additive sedation is possible when antihistamines are used with alcohol, antidepressants, opioid analgesics, and sedative hypnotics. Antidopaminergic drugs, when taken with alcohol or other CNS depressants, will increase CNS depression. Increased CNS depression occurs when alcohol is taken together with metoclopramide. Anticholinergics and Analgesics The motility effects of metoclopramide can be blocked by anticholinergics and analgesics. There are no significant drug interactions with serotonin blockers and cannabinoids.

Pharmacodynamics of Anticholinergics

Anticholinergics work in several ways. When they are working as antiemetics, they bind to acetylcholine receptors deep within the vestibular nuclei of the brain. This action blocks the nausea-inducing signal from communicating to the CTZ. When reticular formation receptors are blocked, the nausea-inducing signals are prevented from transmitting to the vomiting center. In addition, with dehydration of GI secretions and a reduction in smooth muscle spasms from anticholinergic presence, acute GI symptoms (nausea and vomiting) are reduced. Scopolamine The main anticholinergic used as an antiemetic is scopolamine. Scopolamine blocks the binding of acetylcholine to the receptors in the vestibular nuclei, the areas of the brain for balance control. An imbalance between acetylcholine and norepinephrine is corrected by this action. Based on these effects, scopolamine is the most commonly used medication for prevention and treatment of nausea and vomiting experienced with motion sickness. Postoperative nausea and vomiting are also treated with scopolamine.

Pharmacokinetics of Dopamine Antagonists

Antidopaminergics are metabolized in the liver and GI tract and excreted in the urine, bile, and feces. Prochlorperazine Route IM Onset of Action 30-40 min Peak Plasma Concentration 2-4 hr Elimination Half-life 6-8 hr Duration of Action 3-4 hr Promethazine Route IM Onset of Action 20 min Peak Plasma Concentration 4.4 hr Elimination Half-life 9-16 hr Duration of Action 2-6 hr Lorazepam Route PO Onset of Action 30-60 min Peak Plasma Concentration 2 hr Elimination Half-life 11-16 hr Duration of Action 8 hr

Pharmacodynamics of Antihistamines

Antihistamines (histamine1 [H1] receptor blockers) act very much like anticholinergics by inhibiting vestibular stimulation. Antihistamines' primary action is to bind to H1 receptors. Nausea and vomiting occur when the vestibular and reticular systems are stimulated. The antihistamines block cholinergic stimulation of both of these systems. It is very important to not confuse these medications with histamine₂ (H2) receptor blockers, which are given for control of gastric acid. Meclizine is also used to treat nausea and vomiting from motion sickness, dizziness, and vertigo.

Pharmacokinetics of Cannabinoids

Cannabinoids are metabolized in the liver and excreted mainly in bile, feces, and urine. Dronabinol Route PO Onset of Action 30-60 min Peak Plasma Concentration 1-3 hr Elimination Half-life 19-36 hr Duration of Action 4-6 hr

Pharmacokinetics of Glucocorticoids

Dexamethasone is primarily excreted in the urine and minimally removed by hemodialysis. Absorption: Rapidly absorbed from GI tract after PO administration Distribution: Widely distributed Protein Binding: High Metabolism: Metabolized in liver Excretion: Primarily excreted in urine Minimally removed by hemodialysis Half-life: 3-4.5 hrs

Pharmacodynamics of Dopamine Antagonists

Dopamine antagonists include phenothiazines, butyrophenones, and benzodiazepines. These drugs prevent nausea and vomiting by blocking dopamine 2 receptors in the CTZ. Phenothiazine Antiemetics Nausea and vomiting related to surgery, anesthetics, chemotherapy, and radiation are treated with selected phenothiazines, which inhibit the CTZ. The first phenothiazines used for vomiting and psychosis were chlorpromazine and prochlorperazine. Promethazine, the most regularly prescribed antiemetic, was first used as an antihistamine in the 1940s. Promethazine, which has a sedative effect, can also be used for motion sickness, nausea, and vomiting. Benzodiazepines Nausea and vomiting due to cancer chemotherapy can be treated with select benzodiazepines. Diazepam was the preferred benzodiazepine, but now lorazepam is preferred. When used in combination with a glucocorticoid and a serotonin (5-HT3) receptor antagonist, lorazepam can provide emesis control, sedation, and amnesia and can reduce anxiety.

Dosage and Administration of Antiemetics

Drug (Pregnancy Category) Anticholinergics: scopolamine (C) Pharmacologic Class Anticholinergic, belladonna alkaloid Usual Dosage Range Apply 1 patch to hairless area behind ear every 3 days (starting at least 4 hr before travel) Indications/Uses Motion sickness prophylaxis Drug (Pregnancy Category) Antihistamines ; meclizine (B) Pharmacologic Class Anticholinergic, antihistamine Usual Dosage Range Adult PO: 25-50 mg 1 hr before travel and repeated daily during travel PO: 25-100 mg/day, divided 1-4 times daily Indications/Uses Motion sickness prophylaxis Treatment of vertigo Drug (Pregnancy Category) Antidopaminergics; prochlorperazine (C), promethazine (C) Pharmacologic Class Phenothiazine Usual Dosage Range Pediatric Doses vary based on weight and age Adult PO: 5-10 mg 3-4 times daily IM: 5-10 mg q3-4h (max 40 mg/day) PR: 25 mg twice daily IV: 5-10 mg q6h Pediatric older than 2 yr IV, IM, PO, PR: 0.25-0.5 mg/kg/dose 4-6 times daily Adult IV, IM, PO, PR: 12.5-25 mg q4-6h Indications/Uses Antiemetic Drug (Pregnancy Category) Serotonin Blockers; ondansetron (B) Pharmacologic Class Antiserotonergic Usual Dosage Range Pediatric Doses vary based on age and weight Adult PO: 8 mg tid Adult IV: 24-32 mg once daily Pediatric: 1 mo-12 yr Less than 40 kg: 0.1 mg/kg More than 40 kg: 4 mg as single dose Adult 4 mg as single dose 30 min before surgery ends Indications/Uses Chemotherapy antiemetic Prevention and treatment of postoperative nausea Drug (Pregnancy Category) Tetrahydrocannabinoids; dronabinol (C) Pharmacologic Class Marijuana-derived antiemetic Usual Dosage Range Adult PO: Initially, 5 mg/m2 1-3 hr before chemotherapy, then q2-4h after chemotherapy up to 6 times daily for 3 days; this dose may, if needed, be increased in 2.5-mg/m2 increments to a max dose of 15 mg/m2 Adult PO: 2.5 mg twice daily before lunch and before or after dinner to a maximum dose of 20 mg/day in divided doses. Adverse effects increase greatly in doses above 20 mg/day Indications/Uses Chemotherapy antiemetic Appetite stimulation in HIV/AIDS and cancer patients

Contraindications for Antiemetics

Drug allergy is the primary contraindication for all antiemetics. Various specific drugs have other contraindications. Antihistamines Meclizine Contraindicated for women who are lactating and for patients with a recent history of shock. Anticholinergics Scopolamine Contraindicated in patients with glaucoma. Dopamine Antagonists Prochlorperazine Contraindicated in comatose patients, those with hypersensitivity to phenothiazine, and patients with seizures, encephalopathy, or bone marrow depression. Promethazine Children under 2 years of age should not take this medication. Serotonin Antagonists Ondansetron Only contraindication is known drug allergy Cannabinoids Dronabinol Only contraindication is known drug allergy Glucocorticoids Dexamethasone Contraindicated in patients with hypersensitivity to the drug or class of drugs and patients with systemic fungal infections or cerebral malaria. Cautions: Immunosuppression, renal/hepatic impairment, thyroid disorder, cardiovascular disease, post MI, diabetes, glaucoma, cataracts, myasthenia gravis, seizures, older adult patients, osteoporosis.

Patient Teaching for Antiemetics

General Teaching Instruct the patient that antiemetics need to be stored in an airtight, light-resistant container (if required). While on prescription antiemetics, patients should avoid any OTC preparations. Patient should be warned to abstain from alcohol while on antiemetics. Increased sedation will occur with this combination. Due to the risk of teratogenic effects, pregnant patients should be advised to avoid antiemetics during first trimester. If needed, they should consult their health care provider regarding OTC and prescription antiemetics. Side Effects Instruct the patient to follow up with the health care provider if mouth lesions, fever, or sore throat develop. The provider will draw blood for CBC. Due to drowsiness from antiemetics, the patient should avoid driving motor vehicles or participating in dangerous activities. Decreasing dosage may be indicated if drowsiness becomes a problem. Caution patients with hepatic disorders to seek medical advice before taking phenothiazine. Instruct patients to report dizziness. Nonpharmacologic methods such as flat soda, weak tea, crackers, and dry toast should be utilized to alleviate nausea and vomiting. Cultural Considerations Cultural beliefs regarding nonprescription and prescription therapy for nausea and vomiting need to be respected. Review the safety and purpose of nonprescription and prescription therapy. If needed, an interpreter should be provided for non-English speaking patients when assessing, administering medication, providing education, or evaluating the effectiveness of antiemetic therapy.

Pharmacodynamics of Glucocorticoids and Cannabinoids

Glucocorticoids and cannabinoids are used to treat nausea and vomiting in cancer patients. Glucocorticoids Dexamethasone and methylprednisolone suppress vomiting induced by cancer chemotherapy. The side effects associated with glucocorticoids are minimal due to IV administration and short course Cannabinoids Nausea and vomiting associated with cancer treatments can be alleviated with cannabinoids (active ingredients in marijuana). They have been approved for clinical use since 1985. If there is no response or the patient is unable to take other antiemetics, cannabinoids may be prescribed for those receiving chemotherapy. They can also be used in the treatment of AIDS (acquired immunodeficiency syndrome) as an appetite stimulant.

Evaluation of Antiemetic Therapy Effects

It is essential for the nurse to evaluate the effects of antiemetic therapy on the patient. Evaluate the effectiveness of therapy, nonprescription, and prescription antiemetics. Identify tolerance of drug therapy and note any side effects. Check vital signs and compare. Dehydration may occur with severe vomiting. If so, look for hypotension and tachycardia. Monitor bowel sounds for hypoactivity or hyperactivity. Document intake and output. Provide and encourage mouth care after vomiting to maintain oral hygiene

Pre-Administration Assessment for Antiemetics

It is essential for the nurse to perform a patient assessment prior to the administration of antiemetics. Assessment questions may include: Is there any possibility you may be pregnant? Have you been able to take your prescribed medications the past two weeks? What precipitated the symptoms? Have you had a fever recently? Have you been eating any foods out of the ordinary? Have you noticed your tongue or stools turning black? Determine Baseline Data When obtaining patient history, the nurse needs to assess onset and frequency of nausea and vomiting and contents and amount of vomitus. Obtain medication history including prescription and OTC drugs. Determine possible causes. Check vital signs and monitor bowels sounds for hyperactivity and hypoactivity. If vomiting is severe, the patient may become hypotensive due to dehydration. Identify High-Risk Patients Obtain a history of present health problems and medications. Some patients, such as those with glaucoma, should avoid many of the antiemetics. Conduct Ongoing Assessments Record vital signs for baseline and comparison. Assess urinalysis before and during therapy. Document intake and output. Provide and encourage mouth care after vomiting to maintain oral hygiene.

Pharmacokinetics of Antihistamines

Meclizine is well absorbed from the GI tract, metabolized in the liver, and excreted primarily in urine and is widely distributed throughout the body. Route PO Onset of Action 1hr Peak Plasma Concentration Variable Elimination Half-life 6hr Duration of Action 8-24hr

Case Study

Ms. Smith, a 35-year-old patient, was admitted to the hospital for nausea and vomiting. Her symptoms have persisted for 2 weeks without responding to OTC therapy, dry toast, and flat soda. The RN learns that Ms. Smith is currently on losartan for hypertension and simvastatin for cholesterol. Ms. Smith is also taking bismuth subsalicylate and calcium carbonate antacid. Her vital signs are BP 98/50, HR 98, and O₂ Sat 93% on room air. Upon assessment, Ms. Smith's lungs are clear and her abdomen is soft but has hypoactive bowel sounds. Prochlorperazine IV (a dopamine antagonist drug) was given in the emergency department and is ordered as needed for nausea and vomiting.

Pharmacokinetics of Serotonin Antagonists

Ondansetron is metabolized in the liver and excreted in urine. Route IV Onset of Action 15-30 min Peak Plasma Concentration 1-1.5 hr Elimination Half-life 3.5-5 hr Duration of Action 6-12 hr

Pharmacodynamics of Serotonin Antagonists

Ondansetron, granisetron, dolasetron, and palonosetron are serotonin antagonists. By blocking the serotonin receptors in the CTZ and the afferent vagal nerve terminals in the upper GI tract, they suppress nausea and vomiting. These drugs are the most effective in suppressing nausea and vomiting due to cancer chemotherapy, induced emesis, or emetogenic anticancer therapy. Because they do not block dopamine receptors, ondansetron, granisetron, and dolasetron do not cause extrapyramidal symptoms (EPS). However, they can be used to prevent pre- and postoperative nausea and vomiting.

Pharmacokinetics of Anticholinergics

Scopolamine is metabolized in the liver and excreted in urine. This preparation is used frequently as prophylaxis for nausea related to motion sickness. It is typically placed behind the ear. Route Transdermal Onset of Action 1-2 hr Peak Plasma Concentration 6-8 hr Elimination Half-life 8-9.5 hr Duration of Action 72 hr

Summary

There are two major groups of antiemetics: nonprescription (antihistamines, bismuth subsalicylate, and phosphorated carbohydrate solution) and prescription (antihistamines, anticholinergics, dopamine antagonists, benzodiazepines, serotonin antagonists, glucocorticoids, and cannabinoids). Many of these drugs act by blocking the dopamine, histamine, serotonin, and acetylcholine receptors, as these receptors are associated with vomiting. The nurse's role in prescribing antiemetics is essential to make certain the goal of patient safety is achieved. The nurse needs to not only perform a patient assessment prior to the administration of antiemetics, but must also evaluate the effects of antiemetic therapy on the patient. Therefore, the evaluation must include noting nonprescription and prescription antiemetics used, identifying drug therapy tolerance and any noted side effects, comparing vital signs, checking bowel sounds, and documenting patient intake and output. The nurse also needs to take into consideration patient teaching and cultural beliefs when discussing antiemetic administration with the patient.

Overview of Antiemetics

Vomiting (emesis) is the ejection of gastric contents through the mouth. Vomiting can be caused by many things, including viral and bacterial infections, intolerance of different foods, motion sickness, middle ear disturbances, shock, surgery, and certain cancer treatments such as chemotherapy and radiation. Nausea is a queasy feeling that may be felt prior to vomiting. Prescription antiemetics should not be administered until the source of vomiting is identified, as they can mask the true cause of the vomiting. If vomiting is severe enough to cause electrolyte imbalances and dehydration, then antiemetics should be administered. Classification There are two major cerebral centers found in the medulla. The CTZ—or chemoreceptor trigger zone—and the vomiting center can cause vomiting if stimulated. The CTZ can be stimulated by impulses received from toxins, drugs, and the vestibular center of the ear. These impulses are then sent to the vomiting center. There are two major groups of antiemetics, nonprescription and prescription. Nonprescription antiemetics include antihistamines, bismuth subsalicylate and phosphorated carbohydrate solution. Prescription antiemetics include antihistamines, anticholinergics, dopamine antagonists, benzodiazepines, serotonin antagonists, glucocorticoids, cannabinoids, and other various antiemetics. Several nonprescription drugs, such as bismuth subsalicylate, act directly on the gastric mucosa to suppress vomiting. Mechanism Many of these drugs act by blocking the dopamine, histamine, serotonin and acetylcholine receptors. These receptors are associated with vomiting. Antihistamines and anticholinergics act primarily on the vomiting center. They also can decrease stimulation to the CTZ and vestibular pathways. Cannabinoids affect the cerebral cortex. The CTZ center can be acted on by phenothiazine (e.g., metoclopramide) and trimethobenzamide. For chemotherapy induced nausea and vomiting, a combination therapy is commonly used. The combination is usually comprised of lorazepam, glucocorticoids, and serotonin (5-HT3) receptor antagonists. The mixture of lorazepam, haloperidol, and glucocorticoids is a highly effective antiemetic, but this is an off label use.