Lecture 12 - Nausea and Vomiting Part 2

what are the main neurotransmitters involved in motion sickness

Vestibular centre - acetylcholine and histamine

what are non-pharm treatments for motion sickness

Stable visual point: Clear forward view, minimal head movements

Avoid visual/non-visual stimuli that exacerbate (reading, odors, smoking)

Acupressure points (Seabands®) - though not shown to be effective could be tried if mild symptoms

Diet: avoid eating within 3 hours of travel, avoid dairy products or high in protein/calories, or sodium

Increase ventilation

On a boat: Sit in Central area

Avoid visual stimuli that can be triggers: 3D movies, intense video game graphics

what are pharmacologic options for motion sickness

Anticholinergics

Antihistamines

how should anticholinergics and antihistamines be used for short duration of motion sickness

dimenhydrinate (OTC), alternate – diphenhydramine(OTC) or hydroxyzine (Rx)

Start 60 min before activity for dimenhydrinate, can repeat q4 – 6 hours for immediate release, q8-12 hr for long acting

Consider promethazine if patient does not respond to dimenhydrinate (note: promethazine longer duration of action), start no later than 30-60 min before activity but may take up to 2 hours for onset.

what should be considered if patients do not respond to treatment with dimenhydrinate

promethazine

(note: promethazine longer duration of action), start no later than 30-60 min before activity but may take up to 2 hours for onset.

what is N/V of pregnancy

Common in first trimester – 75% of women

Severity varies among patients

Avg: onset around 4 weeks, peaks at 9 weeks, usually disappears by week 20

Morning sickness is a misnomer (NVP can occur at any time of the day)

• If worse in am, keep crackers at bedside

what is hyperemesis gravidarum

1 – 3%

Severe NV, requires hospitalization

what is the cause of N/V of pregnancy

unknown, high estrogen levels?

NV correlates with human chorionic gonadotropin (hCG)

what are non-pharm treatments for N/V of pregnancy

Diet – small, bland meals

Eat at times of the day when nausea is less

Eat cold foods (hot foods may bother and have stronger scents)

Drink fluids

Acupressure

Ginger – mild NVP (1 g divided doses – eg. 250 mg q6h)

what prescription options are available for mild N/V of pregnancy

DiclectinTM – Rx

• pyridoxine (vitamin B6) 10mg + doxylamine 10mg delayed release

Pyridoxine alone

• B-natal (25mg q8h)

what are side effects of diclectin

drowsiness, disorientation, diarrhea

what is recommended for moderate-severe NVP

Dimenhydrinate – 3rd or 4th line (after pyridoxine, diclectin, ginger).

Also diphenhydramine or promethazine can be an option

what is the next step if dimenhydrate is ineffective for moderate-severe NVP

Phenothiazines – chlorpromazine, prochlorperazine

Metoclopramide

what are complications of hyperemesis gravidarum

dehydration, electrolyte disturbances can occur

If ongoing – nutritional/malnutrition

Often requires hospitalization

what is the management of hyperemesis gravidarum

IV fluids/electrolyte replacement

May consider any of the following

• Phenothiazines

• Metoclopramide

• Ondansetron

• Corticosteroids for refractory – methylprednisolone

what are the recommendations for ondansetron in pregnancy

May be used clinically for severe/persistent NV or hyperemesis gravidum

small increase in orofacial malformations when administered in 1st trimester

what are risk factors for postoperative NV

female

nonsmokers (smokers have induced enzymes that clear anesthesia chemicals faster than non-smokers)

history of PONV/motion sickness

post-op opioid use

what are other less important risk factors for PONV

Anesthesia considerations:

• use of nitrous oxide (or volatile anesthetics), use of general anesthesia (vs local), longer anesthetic time

type of surgery

• abdominal, gynecologic, eye, ear/nose/throat surgeries higher risk

Post Op factors: Opioid use and pain

how is the risk of PONV assessed

Base risk on important risk factors:

≥ 2 risk factors or history of PONV

how is moderate risk of PONV managed (2 risk factors)

consider 1 – 2 anti-emetics

how is moderate risk of PONV managed ( ≥3-4 risk factors)

2 anti-emetics before surgery

what therapies are available as PONV prophylaxis

5-HT3 RA (granisetron, ondansetron)

Dexamethasone

Dimenhydrinate

Phenothiazines (promethazine)

NK1 RA (aprepitant, fosaprepitant)

what are factors to consider when selecting therapy for PONV

Timing of administration

Consider goal of prevention vs treatment of PONV

Consider side effect profile

Cost and formulary issues

what is acute antineoplastic-induced NV

Occurs within the first 24 hours after exposure to antineoplastic agents

Onset within a few minutes to several hours after drug administration

Intensity peaks after 5-6 hours

Resolves in approximately 24 hours

what is delayed antineoplastic-induced NV

Onset is 24 hours or more after chemo administration

Common with Cisplatin and Cyclophosphamide with Doxorubicin (AC combination)

Maximal intensity at 48-72 hours post chemo and can last 6-7 days

More common than acute (approximately 68% vs 34%)

what is anticipatory AINV

Occurs before patients receive their next chemotherapy treatment

Considered a conditioned response

what is breakthrough AINV

Nausea or vomiting that occurs despite prophylactic treatment and/or requires rescue with antiemetic agents

what is refractory AINV

Nausea and/or vomiting that occurs during subsequent treatment cycles when antiemetic prophylaxis and/or rescue have failed in earlier cycles

what is Emetic Risk

the risk to cause vomiting in patients that don’t receive prophylaxis.

High (>90%), moderate(30-90%), low (10-30%), minimal <10%)

what is IV HEC

“highly emetogenic IV chemotherapy”

what is IV MEC

“moderately emetogenic IV chemotherapy”

what is the most important factor when assessing risk of antineoplastic induced NV

emetic risk

what are examples of high emetic risk drugs

Cisplatin

Cyclophosphamide > 1500mg/m2

Anthracycline + Cyclophosphamide (AC combo)

what are examples of moderate emetic risk drugs

Carboplatin or Oxaliplatin

Cyclophosphamide < 1500mg/m2

Anthracyclines (Doxorubicin, Epirubicin)

what are examples of low emetic risk drugs

Docetaxel or Paclitaxel

Fluorouracil

what are examples of minimal emetic risk drugs

Vincristine, Vinorelbine

what are risk factors for AINV

Biological Sex - Females at higher risk than males

Past alcohol consumption - high alcohol consumption (past or present alcoholism) is associated with less nausea

History of motion sickness/NVP - Positive history of motion sickness and/or NVP is associated with higher risk for AINV

Age - younger age (<50) associated with higher risk

Previous AINV - Previous treatments or previous cycles of current treatment

what are the principal neuroreceptors involved in AINV

Serotonin (5-HT3)

Dopamine

Neurokinin 1 (NK-1)

what are other neuroreceptors involved in AINV

Acetylcholine

Corticosteroid

Histamine

Cannabinoid

Opioid

how is prophylaxis for a highly emetogenic chemo managed in acute AINV

three or four drugs given pre-chemo

how is prophylaxis for a moderately emetiogenic chemo managed in acute AINV

two or three drugs given pre-chemo

how is prophylaxis for a low emetogenic chemo managed in acute AINV

one drug option: dexamethasone, 5HT3 RA, prochlorperazine, or metoclopramide

how is prophylaxis for delayed AINV managed

5-HT3 receptor antagonists (ondansetron/granisetron) are inconsistent in efficacy for delayed, therefore not continued after chemo is administered

NK1-RA, dexamethasone, or olanzapine continued for day 2 – 4

what is Akynzeo

NK-1 Antagonist/5-HT3 Receptor Antagonist combination

netupitant 300 mg and palonosetron HCl 0.5mg as a single capsule

Can replace separate doses of ondansetron/granisetron plus aprepitant to prevent acute and delayed AINV.

what drugs are commonly used to have on hand in case of breakthrough NV

Metoclopramide

Prochlorperazine

Olanzapine (if not already receiving the maximum dose as part of prophylactic regimen)

Nabilone

Watch for DRUG INTERACTIONS!

how is anticipatory AINV managed

More difficult to treat

May require benzodiazepines such as lorazepam prior to chemotherapy

Others: behavioral therapy, mindfulness

what is management for radiation therapy NV based on

emetogenic risk

what is recommended for high emotogenic risk RTNV

Prophylaxis: 5-HT3 antagonist + Dexamethasone

Administer before each treatment

what is recommended for moderate emotogenic risk RTNV

5-HT3 Antagonist

Optional: Dexamethasone

Pre-treatment and 24 hours post if symptoms persist

what is recommended for low emotogenic risk RTNV

Prophylaxis not always mandatory but recommended

5-HT3 antagonist - scheduled or prn

what is recommended for minimal emotogenic risk RTNV

No routine prophylaxis required

Rescue: metoclopramide or 5-HT3 antagonist

what is the most common cause of NV in children

viral gastroenteritis

Natural course

• Prevent dehydration and electrolyte imbalance with oral rehydration solutions (ORS)

• IF nausea symptoms greater than 24 hours then REFER

what non-pharm treatment is recommended for NV in children

Small meals

Prevent motion sickness in cars – improve ventilation

what antiemetics can be used for NV in children

Dimenhydrinate – recommended for >2 years (note: <1 year not recommended, <2 years under advice of physician)

Diphenhydramine as alternative (for >6 years)

• Note: some children exhibit paradoxical excitability with the antihistamines

what is the role of the pharmacist for NV

Assess patients

• Focus on cause

• Know when to refer patients

Treat underlying cause when appropriate

• Discuss non-pharmacologic measures

• Understand what therapies help the different kinds of NV.

• Understand where non-prescription therapies can be used.

Monitor/Follow-up – what would you tell patients?