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Nausea and vomiting during chemotherapy

By Irish Pharmacist - 01st Aug 2023

The reasons why this happens and medications used to counteract it

As a pharmacist, it is important to understand the different types of chemotherapy to help educate patients and ensure they receive the best possible care and to help advise on anti-emetic options, as choice varies depending on the type of chemotherapy used, as well as individual patient characteristics. Chemotherapy is the use of drugs to treat cancer, and there are different types available, depending on the type and stage of cancer being treated. The top-five most common cancers in Ireland are:


1. Breast cancer: Breast cancer is the most frequently diagnosed cancer in Ireland, affecting mainly women, but also men.

2. Prostate cancer: Prostate cancer is the second-most common cancer in Ireland and affects males only. It is also the most survivable of all cancers.


3. Lung cancer: Lung cancer is the third-most common cancer in Ireland, predominantly caused by smoking, but also affecting non-smokers.


4. Colorectal cancer: Colorectal cancer, which includes both colon and rectal cancer, is the fourth-most common cancer in Ireland.


5. Skin cancer: Skin cancer, including melanoma and non-melanoma skin cancers, is the fifth-most common cancer in Ireland, primarily caused by excessive exposure to sunlight.

The most common types of chemotherapy used in Ireland

1.Alkylating agents

These drugs work by interfering with the DNA inside cancer cells, preventing them from dividing and multiplying. Examples of alkylating agents include cyclophosphamide, cisplatin, and carboplatin. These drugs are commonly used to treat breast cancer, ovarian cancer, and different types of leukaemia and lymphoma.

2. Antimetabolites

Antimetabolites work by blocking the production of DNA, preventing cancer cells from dividing and growing. Examples of this type of chemotherapy include methotrexate, 5-fluorouracil, and capecitabine. These drugs are commonly used to treat breast, colorectal, and lung cancer, as well as leukaemia and lymphoma.

3. Anthracyclines

Anthracyclines are a class of drugs that work by blocking the enzymes that cancer cells need to divide and grow. They are commonly used to treat breast cancer, leukaemia, and lymphoma. Examples of anthracyclines include doxorubicin, epirubicin, and idarubicin.

4. Platinum compounds

Platinum compounds work by preventing cancer cells from repairing themselves after they have been damaged by chemotherapy. These drugs are commonly used to treat testicular, ovarian, and lung cancer, as well as some types of lymphoma. Examples of platinum compounds include cisplatin, carboplatin, and oxaliplatin.

5. Taxanes

Taxanes work by interfering with the production of microtubules, which are essential for cancer cells to divide and grow. These drugs are commonly used to treat breast, ovarian, and lung cancer. Examples of taxanes include paclitaxel, docetaxel, and cabazitaxel.

6. Topoisomerase inhibitors

Topoisomerase inhibitors are a class of chemotherapy drugs that work by interrupting the DNA replication process within cancer cells. This prevents them from dividing and growing. Examples of topoisomerase inhibitors include etoposide, irinotecan, and topotecan. They are commonly used to treat lung, ovarian, and colorectal cancer, as well as leukaemia and lymphoma.

7. Monoclonal antibodies

Monoclonal antibodies are a type of biological therapy that work by targeting specific proteins on the surface of cancer cells, allowing the immune system to recognise and destroy them. Examples
of monoclonal antibodies used in chemotherapy include bevacizumab, trastuzumab, and rituximab. They are commonly used to treat breast, lung, and colorectal cancer, as well as lymphoma.

CHEMOTHERAPY IS OFTEN ONLY ONE PART OF CANCER TREATMENT

Chemotherapy is often used in combination with other treatments, such as surgery and radiation therapy, to achieve the best possible outcome. The choice of chemotherapy drugs will depend on factors such as the type and stage of cancer being treated, the patient’s overall health, and any other medical conditions they may have. Cancer care teams will educate patients about the potential side-effects of chemotherapy, which can include nausea, fatigue, hair loss, and an increased risk of infection, but it’s important for pharmacists to be knowledgeable of side-effects so they can also support the patients dealing with and counteracting these treatments. Patients should be informed about which side-effects are common and which ones require immediate medical attention. It is also important to monitor patients closely for any signs of adverse reactions to chemotherapy drugs and to communicate with the medical team to ensure that proper care is being provided.

HOW DO NAUSEA AND VOMITING COMPARE BETWEEN CHEMOTHERAPY VERSUS RADIATION TREATMENT?


Both chemotherapy and radiation treatment for cancer can cause nausea and vomiting as common side-effects, but the frequency and severity may vary between the two treatments. In general, chemotherapy is often associated with a higher risk of developing nausea and vomiting compared to radiation therapy. This is because chemotherapy drugs target rapidly dividing cells in the body, including those in the digestive system, which can lead to gastrointestinal side-effects. The intensity of these side-effects can vary depending on the specific chemotherapy drugs used, the dosage, and the individual’s tolerance. Radiation therapy, on the other hand, primarily targets the cancer cells within a specific area of the body. While radiation can cause gastrointestinal upset, it is less likely to cause severe nausea and vomiting as compared to chemotherapy. However,
if radiation treatment is focused on the abdominal or gastrointestinal region, it may lead to symptoms such as nausea, vomiting, and diarrhoea. For this reason, I am concentrating on discussing drugs to prevent nausea and vomiting due to chemotherapy in this article; however, many of the anti-emetics used to counteract nausea and vomiting due to chemotherapy are the same ones that will be used to counteract nausea and vomiting due to radiation.

REASONS FOR NAUSEA AND VOMITING DURING CHEMOTHERAPY


Chemotherapy is the most-used cancer treatment and involves administering drugs that target and kill rapidly-dividing cancer cells. However, chemotherapy drugs also affect healthy cells in the body, including those in the digestive system, leading to various side-effects. One of the most common side-effects of chemotherapy is nausea and vomiting, which can significantly impact a patient’s quality-of-life. Chemotherapy-induced nausea and vomiting (CINV) is caused by the release of certain chemicals in the body, such as serotonin and dopamine, in response to chemotherapy drugs. These chemicals stimulate the parts of the brain responsible for controlling nausea and vomiting, leading to these symptoms. According to a study published in the Irish Medical Journal, up to 70 per cent of cancer patients in Ireland reported experiencing CINV during their treatment. This high rate is due to several factors, including the type and dosage of chemotherapy drugs used, the age and gender of the patient, and their previous experience with the treatment. The type of chemotherapy drug used is a significant factor in determining the severity and frequency of CINV. Some chemotherapy drugs are more likely to cause nausea and vomiting than others. For example, the drug cisplatin is highly emetogenic, meaning that it causes significant nausea and vomiting in most patients. Other drugs, such as carboplatin and paclitaxel, are less emetogenic, but can still cause these symptoms in some patients. The dosage of chemotherapy drugs is also an important factor in determining the risk of CINV. Higher doses of chemotherapy drugs are more likely
to cause severe nausea and vomiting. However, reducing the dosage of chemotherapy drugs can also affect their effectiveness in treating cancer, so finding the right balance is crucial. The age and gender of the patient are also significant factors in determining the risk of CINV. Women are generally more likely to experience CINV than men, and younger patients are more susceptible than older patients. This may be because women have higher levels of hormones that can trigger nausea and vomiting, and young people have more sensitive digestive systems. Furthermore, a patient’s previous experience with chemotherapy can affect their likelihood of experiencing CINV. Patients who have had CINV during previous chemotherapy treatments are more likely to experience it again in the future. Therefore, doctors may prescribe anti-nausea medication as a preventative measure for these patients. Doctors and healthcare professionals involved in oncology are aware of the impact of CINV on patients and take steps to mitigate these side-effects. The Irish Cancer Society provides practical advice and tips on how to cope with CINV, such as eating small, frequent meals, avoiding strong-smelling foods, and drinking plenty of fluids. Additionally, anti-nausea medications, such as ondansetron and metoclopramide, can be prescribed to help manage CINV.

MEDICATION PRESCRIBED TO COUNTERACT NAUSEA AND VOMITING FROM CHEMOTHERAPY 5-HT3 receptor antagonists

The first group of anti-emetic drugs used to counteract CINV are the 5-HT3 receptor antagonists. These drugs work by blocking serotonin, a neurotransmitter in the gut that can cause nausea and vomiting. The most used 5-HT3 receptor antagonists in Ireland are ondansetron, granisetron, and palonosetron. Ondansetron is available as tablets, oral solution, and injection, while granisetron and palonosetron are available as tablets and injection. Palonosetron is the most recently developed drug in this group, and it has a longer half-life compared to the other drugs, meaning it lasts longer in the body and can be effective in preventing delayed CINV. These drugs are most effective when given at least 30 minutes before chemotherapy.

Corticosteroids

Another group of anti-emetic drugs used to counteract CINV are the corticosteroids, such as dexamethasone. Corticosteroids are believed to block the production of prostaglandins, which can trigger nausea and vomiting. Dexamethasone is available as tablets and injection. The oral format is mainly used in cancer care. It is often used in combination with 5-HT3 receptor antagonists, as it can improve the effectiveness of these drugs. Dexamethasone can be given before or after chemotherapy.

NK1 receptor antagonists

A third group of anti-emetic drugs used to counteract CINV are the NK1 receptor antagonists, such as aprepitant and fosaprepitant. These drugs work by blocking substance P, a neuropeptide that can trigger nausea and vomiting. Aprepitant is available as capsules and injection, while fosaprepitant is available as injection only. These drugs are most effective when given at least one hour before chemotherapy.

Other anti-emetics

Other anti-emetics used in Ireland to counteract CINV include metoclopramide, which is a dopamine receptor antagonist, and cannabinoids such as dronabinol and nabilone. Metoclopramide is available as tablets and injection. It is often used as a second-line drug when other anti-emetic drugs have failed. Cannabinoids are only used if other anti-emetic drugs are not effective, as they can cause central nervous system side-effects. National Cancer Control Programme (NCCP) guidelines in Ireland recommend 5-HT3 receptor antagonists and dexamethasone for highly and moderately emetogenic chemotherapy, and the addition of aprepitant for highly emetogenic chemotherapy. For low emetogenic chemotherapy, the guidelines recommend metoclopramide or 5-HT3 receptor antagonists as first-line therapy, and cannabinoids as second-line therapy. Pharmacists play an important role in the management of CINV. They can advise patients on the appropriate use
of anti-emetic drugs, including dosage, administration, and side-effects. They can also work with oncologists and other healthcare professionals to ensure that the most effective anti-emetic drugs are used for each patient’s individual needs. Pharmacists can also counsel patients on non-pharmacological techniques that may help reduce CINV, such as acupuncture, acupressure, and relaxation techniques.

SIDE-EFFECTS OF ANTI-EMETIC DRUGS USED IN CHEMOTHERAPY

Most chemotherapy patients who use anti-emetic drugs encounter no side- effects from the anti-emetics, but on rare occasions side-effects can occur. The fact patients undergoing chemotherapy have a weakened immune system due to cancer and the chemotherapy treatment can make them more prone to side-effects. Additionally, it can be hard to decipher if the side-effects being experienced
are due to the cancer symptoms, the chemotherapy, and the other cocktail of drugs chemotherapy patients are often prescribed, or the anti-emetic drugs.

1. Fatigue Many anti-emetics can cause fatigue or drowsiness, which might make the patient feel tired or sluggish. Examples:

  • Ondansetron: Fatigue is listed as a potential side-effect, although it is not very common.
    uPromethazine: Drowsiness and fatigue is a common side-effect of promethazine.
  • Metoclopramide: Fatigue is listed as a potential side-effect, although it is less common compared to other side-effects such as restlessness or dizziness.
  • Prochlorperazine: It is sometimes indicated for treating severe nausea and vomiting. It may cause drowsiness.

2. Headaches Some individuals may experience headaches as a side-effect of anti- emetic medications.
Examples:

  • Metoclopramide.
  • Ondansetron.
  • Prochlorperazine.
  • Promethazine.
  • Domperidone.

3. Constipation or diarrhoea Anti-emetics can lead to changes in bowel movements, resulting in either constipation or diarrhoea. Examples:

  • Ondansetron: While constipation is a more common side-effect of ondansetron, diarrhoea can occur in some cases.
  • Metoclopramide: It can cause both constipation and diarrhoea.
  • Prochlorperazine: Although constipation is reported more frequently, diarrhoea is listed as a possible side- effect of prochlorperazine.
  • Domperidone: Constipation is generally more common, but diarrhoea has been reported.

4. Dizziness or light-headedness Certain anti-emetic drugs may cause dizziness or a feeling of light-headedness. Examples:

  • Ondansetron: May cause dizziness or light-headedness in some.
  • Promethazine: Can also cause drowsiness, dizziness, and light- headedness.
  • Metoclopramide: May cause dizziness, light-headedness, and even involuntary movements in some cases.

5. Sedation Certain types of anti-emetic medications can have sedative effects, causing drowsiness or sleepiness.
Examples:

  • Diphenhydramine: Can cause sedation.
  • Promethazine: Can also cause drowsiness and sedation.
  • Ondansetron: While drowsiness is less common with this medication, it can still occur in some.

6. Loss of appetite Loss of appetite and weight loss is a common problem with chemotherapy. Additionally, some anti-emetics may disrupt sense of taste or reduce appetite, which can contribute to weight loss. Examples of anti-emetics that can cause loss of appetite (although rare in all):

  • Ondansetron.
  • Metoclopramide.
  • Prochlorperazine.
  • Promethazine.

8. Electrolyte imbalances Some anti-emetics can affect the balance of electrolytes, such as potassium and magnesium, in the body. Regular blood tests are usually performed to monitor these levels. While anti-emetics are generally safe and rarely cause significant electrolyte imbalances, certain anti- emetics may have the potential to affect electrolyte levels, particularly when used in high doses or for prolonged periods. Examples:

uMetoclopramide: Although rare, metoclopramide can occasionally cause electrolyte imbalances, such as low
levels of sodium (hyponatraemia) or high levels of prolactin. These imbalances are generally seen with long-term use or if the medication is taken in high doses.

  • Ondansetron: Ondansetron is generally well-tolerated, but in rare cases, it may cause abnormalities in electrolyte levels. Some reported cases have shown changes in sodium, potassium, and magnesium levels, although the occurrences are infrequent and usually not severe.
  • Domperidone: Domperidone may cause changes in electrolyte levels in rare cases. Imbalances such as high levels of prolactin, which can affect the balance of other hormones, are possible.

8. Allergic reactions Although rare, it is possible to develop an allergic reaction to anti-emetic drugs. Symptoms may include rash, itching, swelling, or difficulty breathing. Examples:

  • Ondansetron: In rare cases, it can cause allergic reactions such as rash, itching, hives, swelling, or difficulty breathing.
  • Metoclopramide: Although uncommon, some people may develop allergic reactions to it, including rash, itching,
    or swelling.
  • Promethazine: Can also cause allergic reactions in rare cases. Symptoms may include skin rash, hives, itching, swelling, or difficulty breathing or swallowing.

References upon request

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