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Flashcards in Antiemetics Deck (62)
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1

  • What is the "vomiting center?" (neuronal region within the lateral medullary reticular formation)
  • Coordinates the complex act of vomiting through interactions with which 2 cranial nerves? 
  • High concentrations of what 6 receptors are found in the vomiting center? 

  • Vomiting center = Brainstem
  • CN 8 and 10
  1. Muscarinic (M1)
  2. Histamine (H1)
  3. Neurokinin 1 (NK1)
  4. Dopamine (D2)
  5. GABA
  6. Serotonin (5-HTx)

2

What are the 4 important sources of afferent input to the vomiting center? 

  • Chemoreceptor trigger zone
  • Vestibular system
  • Vagal & Spinal afferent nerves
  • Central Nervous System 

3

Which of the 4 sources of afferent input to the vomiting center? 

  • area postrema is located at the caudal end of the fourth ventricle

  • outside the blood-brain barrier but is accessible to emetogenic stimuli in the blood or cerebrospinal fluid

  • rich in dopamine D2 receptors and opioid receptors, and possibly serotonin 5-HT3 receptors and NK1 receptors

Chemoreceptor Trigger Zone

4

Which of the 4 sources of afferent input to the vomiting center? 

  • important in motion sickness via cranial nerve VIII
  • rich in muscarinic M1 and histamine H1 receptors

Vestibular system

5

Which of the 4 sources of afferent input to the vomiting center? 

  • rich in 5-HT3 receptors
  • irritation of the gastrointestinal mucosa by chemotherapy, radiation therapy, distention, or acute infectious gastroenteritis leads to release of mucosal serotonin and activation of these receptors, which stimulate vagal afferent input to the vomiting center and chemoreceptor trigger zone

Vagal & Spinal afferent nerves (from the GI tract)

6

Which of the 4 sources of afferent input to the vomiting center? 

  • role in vomiting due to psychiatric disorders, stress, and anticipatory vomiting prior to cancer chemotherapy.

Central Nervous System

7

N/V

  • Simple:
    • self limiting, resolves spontaneously, requires only what therapy?
  • Complex:
    • not relieved after tx with what?
    • Progressive deterioration of pt secondary to what? 
    • Usually associated w/ what 2 things? 

Simple:

  • symptomatic therapy

Complex:

  • antiemetics
  • electrolyte imbalances
  • noxious agents or psychogenic events

8

N/V

  • Simple: Pt c/o queasiness or discomfort
  • Complex: what 3 sxs? 

  • weight loss
  • fever
  • abdominal pain

9

What laboratory tests are needed for simple and complex N/V?

  • Simple: None
  • Complex: serum electrolyte concentrations / upper & lower GI evaluation

10

What info besides lab do you need in pts with N/V? 

(4)

•Fluid input and output

•Medication history

•Recent history of behavioral or visual changes, headache, pain, or stress

•Family history positive for psychogenic vomiting

11

  • Treatment of choice for N/V involves identification of what?
  • Combinations of antiemetic agents w/ different mechanisms are often used (especially in pts w/ vomiting due to what??)

  • identification of neurotransmitters involved w/ the emesis
  • chemotherapeutic agents

12

6 main drug therapies for N/V? 

  • Antihistamine - anticholinergics
  • Benzodiazepines***
  • Corticosteroids****
  • 5 HT receptor antagonists
  • Phenothiazines
  • Substance P/Neurokinin 1 receptor antagonist

13

Antacids

  • useful w/ simple N/V
  • What are the 4 products?
  • OTC liquid/oral

  • sodium bicarbonate
  • calcium carbonate
  • magnesium hydroxide
  • aluminum hydroxide

14

What are the names of the 4 "Selective Serotonin 5-HT3 Antagonists"

•Ondansetron (Zofran)

•Granisetron  (Granisol)

•Dolasetron (Anzemet)

•Palonosetron (Aloxi)

15

Serotonin 5-HT3 Antagonists 

  • Potent antiemetic properties
  • Mediated through central 5-HT3 receptor blockade in the vomiting center
  • Mainly through blockade of what and where? 

  • Blockade of peripheral 5-HT3 receptors on extrinsic intestinal vagal & spinal afferent nerves in the chemoreceptor trigger zone

16

  • Antiemetic action of Serotonin 5-HT Antagonists is restricted to emesis attributable to what 2 reasons? 
  • Doesn't work well for what reason?

  1. Vagal stimulation (post-operative)
  2. Chemotherapy
  • Poorly controlled: Motion sickness

17

Serotonin 5-HT3 Antagonists

Odansetron, Granisetron, Dolasetron

  • Serum half life?
  • May be administered how often?
  • Comparable efficacy & tolerability if administered how? 

  • 4 - 9 hours
  • Once daily by oral or IV
  • Equipotent doses

18

Which Serotonin 5-HT Atagonist?

  • Newer intravenous agent that has greater affinity for the 5-HT receptor
  • Long serum half life of 40 hours

Palonosetron

"Be a pal and work 40 hours for me"

19

Serotonin 5-HT Antagonists

  • Undergo what type of metabolism?
  • Eliminated by what two organs?
  • Dose reduction is not required in what 2 patients? 

  • Metabolism: hepatic
  • Eliminated: renal & hepatic
  • geriatric or renal insufficiency

20

Serotonin 5-HT3 Antagonist

  • Dose reduction is required for which drug for patient's with what condition?

  • Ondansetron
  • Hepatic insufficiency

21

Serotonin 5-HT Antagonists

  • Do not inhibit what 2 things?
  • Do not have effects on which 2 motilities?
  • May slow down what??

  • dopamine or muscarinic receptors
  • esophageal or gastric motility
  • colonic transit

22

Which medication?

  • Primary agent for prevention of chemotherapy induced N/V 

Serotonin 5-HT3 Antagonists

23

Serotonin 5-HT Antagonists have little or no efficacy for prevention of what? 

Delayed nausea & vomiting

(occuring >24 hours after chemotherapy when used alone)

24

How do you administer Serotonin 5-HT3 Antagonists so that they are most effective in preventing Chemotherapy induced N/V?

Single dose, IV, 30 mins prior to admin of chemotherapy

*Single oral dose 1 hr prior to chemo may be equally effective*

25

Efficacy of Serotonin 5-HT3 Antagonists is enhanced by combination therapy with what 2 meds? 

  • Corticosteroid (Dexamethasone)
  • NK1-receptor antagonist

26

T/F

  • Serotonin 5-HT3 Antagonists are increasingly being used for Post-operative & Post-radiation N/V
  • Effective in pts undergoing radiation therapy to whole body or abdomen

True

27

Serotonin 5-HT3 Antagonists

  • Well tolerated agents
  • Excellent safety profiles
  • What are the 3 MC reported ADEs?
  • What is a small, but statistically significant finding associated w/ this medication?
    • Which medication is this finding most pronounced in??

  • Headache**, constipation**, dizziness
  • Prolongation of QT interval 
    • Dolasetron

(Know HA & Constipation)

28

Serotonin 5-HT Antagonists

  • Have no significant drug interactions
  • Undergo some metabolism by what system?
  • Do NOT appear to affect metabolism of other drugs
  • Other drugs may reduce clearance of this drug. In this case would the half life increase or decrease??****

  • Hepatic cytochrome P450 system
  • Increase

29

What drug?

  • Provide relief from the delayed emesis associated w/ emetogenic medications 
  • Used in combo w/ selective 5-HT3 (Netupitant & Palonosetron) for acute / delayed emesis prevention

Substance P / Neurokinin 1 Receptor Antagonist

  • Rolapitant
  • Aprepitant
  • Netupitant

30

What are the 4 adverse effects of Substance P / Neurokinin 1 Receptor Antagonists

  • Aprepitant
  • Rolapitant
  • Netupitant

  • Constipation
  • Diarrhea
  • Headache
  • Hiccups