Nausea/Vomiting

Question 1

4 Separate Areas That Drive Nausea/Vomiting

Answer 1

• 1- GI stimulus
• 2- Vestibular System
• 3- CTX (chemoreceptor trigger zone) - area postrema + vagal nuclei
• 4- Higher CNS centers (ex - conditioned food avoidance, disgust/depression causing nausea, anticipatory in chemo tx)

Question 2

3 Steps of Vomiting

Answer 2

• 1- Pre-ejection: raid stomach relaxation and retro-peristalsis
• 2- Retching: abs, intercostal and diaphragm strain against closed glottis; generate pressure
• 3- Ejection: intense contraction of ab muscles while LES and UES open (expel food if pressure in stomach&raquo_space; column of food)

Question 3

When should vomiting be considered seriously (not just self-limiting)?

Answer 3

• Chest or abdominal pain too
• late pregnancy
• blood in stools
• severe headache or severe fever
• older age (risk dehydration)

Question 4

5 Major Anti-Emetic Classes

Answer 4

• M1 Receptor Antagonists (in vestibular nuclei and vomiting center)
• H1 Receptor Antagonists (H1 in vestibular system and vomiting center)
• D2 Receptor Antagonists (CTZ and GI tract)
• 5HT3 Receptor Antagonists (in vomiting center, CTZ and GI tract)
• NK1 Receptor Antagonists (receptors for substance P in CTZ and vomiting center)

Question 5

M1 Receptor Antagonists

Answer 5

Scopalamine (patch)
Hyoscyamine
Dicyclomine

Used mainly in motion sickness

Anti-chol side effects (blind as bat, red as beet, mad as a hatter, dry as a bone, tachy)

Question 6

H1 Receptor Antagonists

Answer 6

Dimenhydrinate
Diphenhydramine
Meclizine
Promethazine

Also motion sickness, post-operative

Drowsiness, urinary retention, vision probs, dry mouth

Question 7

D2 Receptor Antagonists

Answer 7

Metoclopromide (Reglan)
Prochlroperazine Haloperidol

Gastroparesis, gastroenteritis, migraine

Affects basal ganglia; tardive dyskinesia or dystonia esp for metoclopromide

Question 8

5HT3 Receptor Antagonists

Answer 8

Ondansetron (Zofran)
Granisetron
Dolasetron

Post-operative, chemo-induced, gastroenteritis

Constipation (serotonin in gut), QT prolongation (EKG first)

Question 9

NK1 Receptor Antagonists

Answer 9

Aprepitant

Chemo-induced

Headache, dizziness, constipation

Question 10

2 Other Anti-Emetic Drugs That Work in CNS

Answer 10

• Cannabinoid - stimulates CB1 receptor throughout CNS; 2nd line for chemo-induced
  
  • Medical marijuana or pill forms (dronabinol, nabilone)
  • Side effects = paranoia, sleepiness, hunger, etc
• Benzodiazepines - GABAergic; rarely used alone for nausea (lorazepam, alprazolam)
  
  • Side effects = tolerance and sedation

Question 11

2 Paths of Chemo-Induced Nausea and Vomiting

Answer 11

• Chemo –> CTZ –> vomiting center –> emesis

- Also local inc in serotonin –> afferents to vomiting center –> emesis

Question 12

3 Prokinetic Drugs

Answer 12

• Erythromycin - motilin receptor agonist at low doses (in stomach)
• Metaclopramide (Reglan) - D2 antagonist; BUT tardive dyskinesia or dystonia
• Cisapride - RESTRICTED b/c arrhythmias; myenteric Ach release thru serotonin