Why Does Chemotherapy Make People Vomit?

Vomiting.   It’s the first thing people think of when they hear the word chemotherapy.   We all know it happens when people get chemotherapy, but why?

Chemotherapy induced nausea, vomiting and retching are three distinct but intertwined side effects related to many chemotherapy drugs.

  1. Nausea – an  uncomfortable sensation of feeling like you may vomit. Often it’s felt in the back of the throat or the top of the stomach.
  2. Vomiting  – the actual motor reflex that causes the stomach contents to come up
  3. Retching – the attempt to force the stomach contents up without success and is also known as “dry heaving”

These unpleasant side effects can be classified further based on timing of symptoms:

  1. Acute – occurs within the first 24 hours after chemotherapy and peaks around 5-6 hours
  2. Delayed – occurs 24 hours after treatment and can last 5-7 days with a peak 48-72 hours after chemotherapy
  3. Anticipatory – this happens prior to chemotherapy and is a result of anticipating that the nausea is coming from prior experiences with the drug.

Ok, now that the gross stuff is out of the way, how does chemotherapy actually cause all of this misery?  There are multiple mechanisms but they all share a common theme.   The gut is injured and sends up signals to the brain which makes you vomit.   Here is one example:

  • Vomiting is controlled by your brain. Inside your brain, the medulla oblongata to be exact, is a fun little group of brain cells called the vomiting center.  This is the main coordinator of nausea and vomiting and it receives signals from other parts of your body.
    • There are special cells that line the gut called enterochromaffin cells and these get damaged by chemotherapy. When they are damaged they release serotonin which binds to a receptor on a nerve with conducts a signal to the brain that says – hey there is something bothering my stomach, so let’s throw it up.
    • We use this receptor mechanism to our advantage by giving anti-nausea drugs that block the receptor. Thus, even though there is extra serotonin floating around, your brain doesn’t receive the signal and the feelings of nausea and vomiting can be blocked

There are two other areas of the brain involved and two other signaling molecules as you can see in this picture, but the general flow of information from the gut to your brain is similar for all three.

Gut injury to the enterochromaffin cells release signals that are transmitted to the brain which causes nausea and vomiting.

 

This table shows you the “Puke Potential” of drugs, with those drugs at the top causing the most nausea and vomiting and those at the bottom causing the least.   The ones highlighted in bold are ones we use frequently in pediatric oncology.

 

Puke potential (% of patients) Drug Dosage Onset/duration of response (hours)
High (>90%) Cisplatin >50 mg/m2 1.5–56
Cyclophosphamide >1,000 mg/m2 9–28
Dacarbazine 4–24
Mechlorethamine 0.5–24
Moderately high (60%–90%) Cisplatin <50 mg/m2 1.5–56
Cyclophosphamide 750–1,000 mg/m2 9–28
Methotrexate >1,000 mg/m2 4–12
Carboplatin 6–46
Doxorubicin >60 mg/m2 3.5–34
Moderate (30%–60%) Cyclophosphamide <750 mg/m2 9–28
Methotrexate 250–1,000 mg/m2 4–12
Doxorubicin <60 mg/m2

3.5–34

Moderately low (10%–30%) Methotrexate <250 mg/m2 4–12
  Fluorouracil 3–10
Etoposide 3.5–34
Low (<10%) Hydroxyurea 8–48
Vinblastine 3.5–34

Bleomycin

3.5–24

Tamoxifen

12–36

Chlorambucil

48–56

The good news in all of this is that we have many more drugs now to combat nausea and vomiting.  It is pretty rare for someone to be incapacitated from chemotherapy induced vomiting.   Sometimes it takes a little trial and error to get the anti-nausea medications tailored just right, but usually we can come up with a good cocktail to make our kids feel pretty decent.  If you are feeling up for a more in depth discussion on puke, check out this article.

#morethanfour #ChildhoodCancer365

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