Exam 13 - Heme33 - Chemotherapy Induced Emesis

Front 1

It appears that 1970s high-dose ... use was key in making chemotherapy antiemetics an important area of research

Back 1

cisplatin

Front 2

Pathophysiology of CIE:

CIE is coordinated by the Vomiting Center (VC) in the .... Activation of the VC leads to efferent transmission to salivary, vasomotor, and respiratory centers; cranial nerves VIII and X; abdominal muscles, diaphragm, stomach, and esophagus.

Key neurotransmitters that stimulate the VC are Substance P, ..., and ....

Back 2

medulla
serotonin 3 (5-HT3)
dopamine 2 (D2)

Front 3

Chemoreceptor Trigger Zone (CTZ) located in the ..., outside the blood brain barrier (BBB), transmits signals to the VC.

Accessible to either blood-borne or CSF-borne chemotherapy agents.

Key neurotransmitters that stimulate the CTZ are ....(3)

Back 3

area postrema
Substance P, 5-HT3, and D2

Front 4

Enterochromaffin Cells in wall of small intestine release ... in response to chemotherapy.

5-HT3 stimulates vagal and splanchnic afferents through their 5-HT3 receptors, sending signals to the CTZ and/or VC.

Back 4

5-HT3

Front 5

What is key neurotransmitter that is believed to be the most important mechanism of CIE?

Back 5

5-HT3

Front 6

Phases of CIE:

... Phase: Occurs during first 18-24 hours after chemotherapy administration.

... Phase: Occurs greater than 18-24 hours after chemotherapy administration, may last up to 5 days, peak in ...-... days.

... Phase: Occurs before chemotherapy administration, seems to be a conditioned reflex.

Back 6

Acute
Delayed
2-3
Anticipatory

Front 7

History – D2 Antagonists

1980s: High dose ... (1 to 3 mg/kg) found to be highly effective in preventing CIE. Discovery that high dose ... is actually a moderate 5HT-3 antagonist.

Back 7

metoclopramide
metoclopramide

Front 8

History – Corticosteroids:

1980s – Corticosteroids, especially ..., become an integral part of chemotherapy antiemetic regimens.

Back 8

dexamethasone

Front 9

History – summary of antiemetic regimens for highly emetogenic chemotherapy (vomiting in 90% or greater)

-1950s – 1970s: D2 antagonists dominate antiemetic regimens.
-1980s – High dose metoclopramide & dexamethasone are the mainstays.
-1990s – 5-HT3 antagonist plus dexamethasone is standard regimen.
-2000s – Standard regimen is ... antagonist, ..., and ... antagonist.

Back 9

5-HT3
dexamethasone
NK-1

Front 10

Medications: ...

Five agents in class:
Ondansetron (Zofran®)
Granisetron (Kytril®)
Dolasetron (Anzemet®)
Palonosetron (Aloxi®)
Tropisetron (Navoban®)(unavailable U.S.)

SE: very ...; blurred vision, headache

Back 10

5-HT3 Antagonists
mild

Front 11

Medications: NK-1 Antagonists:

One agent in class: ...

At present, approved only for use in combination with other antiemetics to prevent CIE.

Available as oral capsules and injectable for IV use.

Administration unaffected by food.

Side effects include fatigue, dizziness, hiccups, gastritis, diarrhea, & LFT elevations.

Back 11

Aprepitant (Emend®).

Front 12

Medications: ...

Phenothiazines:Prochlorperazine (Compazine®)
Promethazine (Phenergan®) Chlorpromazine (Thorazine®)

Side effects include sedation, hypotension, akathesia, and dystonia. (Promethazine is highest in sedation and hypotension)

Back 12

D2 Antagonists

Front 13

Medications: D2 Antagonists:

Butyrophenones:
-... (Haldol®) & ... (Inapsine®)

Usually used as alternates to phenothiazines when D2 antagonist indicated.

Side effects include sedation, anticholinergic effects, hypotension, akathesia, and dystonia.

Back 13

Haloperidol
Droperidol

Front 14

Medications: D2 Antagonists:

Substituted Benzamides:
-... (Reglan®)
-... (Tigan®)

Side effects include sedation, diarrhea, edema, hypertension (due to Na retention), reversible impotence, akathesia and dystonia (especially in younger patients).

Back 14

Metoclopramide
Trimethobenzamide

Front 15

Medications: Benzodiazepines:

Agents Used in Chemotherapy:
-... (Ativan®) & ... (Xanax®)

No antiemetic mechanism of action.

Prevent anticipatory CIE by producing ... and sedation.

Side effects include sedation, hypotension, hallucinations, urinary incontinence, disinhibition, and motor incoordination.

Back 15

Lorazepam
Alprazolam
antegrade amnesia

Front 16

Medications: Cannabinoids:

... (Marinol®)

Mechanism of action unknown.

Despite tear-jerking testimonials, clinical trials show minimal efficacy, including inhaled forms.

Side effects include drowsiness, dizziness, euphoria, dysphoria, mood changes, orthostatic hypotension, ataxia, hallucinations, time disorientation, and increased appetite.

Back 16

Dronabinol

Front 17

Medications: Miscellaneous

... Hormone (ACTH): One study suggests that a 2 mg IM dose was effective in decreasing the incidence of delayed emesis caused by cisplatin.

... (Zyprexa®): Phase II studies suggests that olanzapine is safe and effective in controlling both acute and delayed emesis from highly and moderately emetogenic chemotherapy.

Back 17

Adrenocorticotropic
Olanzapine

Front 18

Basic principles of CIE prevention:

Patients at Higher Risk for CIE:
-Young, Female, Non-drinkers, with a history of CIE, nausea of pregnancy, and motion sickness.
-The most important risk factor for CIE is ...
-Easier to PREVENT CIE than it is to STOP CIE once it starts.
-Oral antiemetics in proper doses are as effective as the same antiemetics in IV form.

Back 18

the emetogenicity of the chemotherapy regimen.

Front 19

Determining Emetogenicity of a Chemotherapy Regimen:

Newer guidelines by MASCC, NCCN, and ASCO divide chemotherapy medications into four risk groups: High (>...%), Moderate (... to ...%), Low (... to ...%) and Mild (<...%) emetogenicity.

Back 19

90
30 to 90
10 to 30
10

Front 20

Antiemetic Regimens for Highly Emetogenic Chemotherapy:

My recommendations are a combination of MASCC, NCCN, and ASCO.

Most highly emetogenic regimens in today’s practice will be those that contain ... > 50 mg/m2 or ... and ... combinations.

Back 20

cisplatin
doxorubicin and cyclophosphamide

Front 21

Antiemetics for Prevention of Delayed Emesis in Highly or Moderately Emetogenic Chemotherapy:

what are the only 2 drugs effective at preventing N/V after chemo?

Back 21

Dexamethasone and Aprepitant

Front 22

All chemotherapy patients get a ... antiemetic prescription

Back 22

PRN (pro re nata: as the situation demands)

Front 23

special problems:

... Chemotherapy Regimens.
Breakthrough CIE.
Pediatrics.
High Dose Chemotherapy with ....
Split daily chemotherapy regimens.

Back 23

Multi-Day
Stem Cell Transplant