GI Nausea/Vomiting Pharm

Question 1

Where is the “vomiting center” in the brain? What functions does it coordinate?

Answer 1

Near the 4th ventricle in the hindbrain (vagal trigone), near the reticular medulla and dorsal vagal brainstem. The common “endpoint” is the medulla, which receives direct signals from the CTZ, cerebellum, NTS, and higher centers

GI function, pharyngeal muscles, salivation, respiration, cardiovascular function, somatic muscles.

Question 2

How do medications cause nausea/vomiting? Examples?

Answer 2

Detected by the CTZ, and also stimulates vagal afferents in the small intestine

Dopamine agonists, digoxin, opiates, nicotine, cytotoxic agents, chemotherapy, abdominal radiation, alcohol

Question 3

How does infection cause nausea/vomiting? Examples?

Answer 3

GI or systemic infections, such as viral gastroenteritis, bacterial infections, and non-GI infections (otitis media, meningitis, hepatitis), effect the CTZ and vagal afferents

Viral: Hawaii agent, rotavirus, reovirus, adenovirus, Norwalk virus, snow mountain agent.
Bacterial: S. aureus, salmonella, b. cereus, c. perfringens

Question 4

How do GI issues cause nausea/vomiting? Examples?

Answer 4

Obstruction and irritation stimulates vagal afferents, while gagging stimulates the glossopharyngeal and trigeminal afferents.

Functions: gastroparesis, dyspepsia, pseudo-obstruction, IBS
Organic: gastroperesis, scleroderma, SLE, PUD, inflammation, IBD, obstruction

Question 5

How do CNS issues cause nausea/vomiting? Examples?

Answer 5

1) Increased intracranial pressure - acts directly on the medulla
2) Labyrinthine disorders - afferents integrate on the cerebellum which signals the medulla
3) Senses and Emotions trigger “higher brain centers” that integrate on the medulla.

Question 6

How do endocrine issues cause nausea/vomiting? Examples?

Answer 6

They integrate on the CTZ and on vagal afferents. Pregnancy is multifactorial, perhaps with estrogen and progesterone effects.

Uremia, DKA, hypercalcemia, hyper/hypoparathyroidism, Addison’s disease.

Question 7

List some etiologies that are listed as “miscellaneous”

Answer 7

1) Postoperative (esp. with anesthesia)
2) Abdominal Migrains/epilepsy
3) Cardiac: Acute MI, CHF, radioablation
4) Angiography
5) Starvation

Question 8

What are some non-pharmacologic options for nausea and vomiting?

Answer 8

1) Correct fluid/electrolyte abnormalities
2) Identify and treat the underlying cause
3) Eat small, low fat meals (esp. gastroparesis) - fat slows gastric emptying
4) Control sugar (esp. gastroparesis) - hyperglycemia delays gastric emptying
5) Ginger and cola syrup are helpful

Question 9

Scopolamine

Answer 9

C: Anticholinergic (central anti-emetic)
MOA: Blocks M1 receptor in CTZ, NTS, cerebellum, and peripheral tissues
ADRs: anti-SLUDGE
Uses: Prophylaxis of motion sickness, limited by side-effects otherwise

Question 10

Meclizine, Diphenhydramine, Cinnarizine, Cyclizine, Hydroxyzine

Answer 10

C: Antihistamine (central anti-emetic)
MOA: Blocks H1 receptor in the cerebellum and NTS
ADRs: drowsiness
Uses: Good for labyrinthine causes (motion sickness, vertigo, migraine)

Question 11

Prochlorperazine, Promethazine, Chlorpromazine, Thiethylperazine, Perphenazine

Answer 11

C: Dopamine Antagonist (central and peripheral anti-emetic)
MOA: Blocks D2 receptors in the CTZ, NTS, and GI smooth muscle
ADRs: sedation, orthostatic hypotension, dystonia, tardive dyskinesia
Uses: Severe motion sickness, vertigo, migraines, GERD, gastroparesis, and functional dyspepsia. Chlorperazine for postoperative and postchemotherapy management.

Question 12

Benzamide, Benzoquinamide, Trimethobenzamide, Metoclopramide, Domeperidone

Answer 12

C: Dopamine antagonist (central anti-emetic)
MOA: Blocks D2 receptor in the CTZ, NTS, and GI smooth muscle
ARDs: Most have limited side effects. Metoclopramide crosses the BBB, causing dystonia, dyskinesia, and hyperprolactinemia
Use: Gastroparesis associated nausea

Question 13

Ondansetron, Granisetron

Answer 13

C: Serotonin antagonist (central and peripheral anti-emetic)
MOA: Blocks 5HT3 receptor in the NTS, CTZ, and vagal afferents in the stomach and small bowel.
ADRs: constipation, headache
Use: Great in post-chemotherapy nausea.

Question 14

Dronabinol, Nabilone

Answer 14

C: Cannabinoids (central anti-emetics)
MOA: Stimulates cannabinoid receptors in the NTS, CTZ, and higher brain centers.
ADRs: sedation, hypotension, ataxia, dizziness, euphoria.
Use: Anorexia, AIDS, and chemotherapy associated vomiting (no scientific evidence)

Question 15

What drugs are used in combination with corticosteroids? Benzodiazepines?

Answer 15

Corticosteroids (dexamethasone, methylprendisilone) used with metoclopramide, ondansetron

Benzos (lorazepam, alprazolam) used with ondansetron

Question 16

Where do prokinetic agents work?
What etiologies are they best used in?
What are the issues with them?

Answer 16

• Peripherally for the most part
• GERD, gastroparesis, dysmotility syndromes, intestinal pseudo-obstruction
• People develop tolerance. Also, ubiquitous receptors lead to CNS and CV side-effects

Question 17

What are the prokinetic agents? What are their targets?

Answer 17

1) Cholinergics: M2 receptors, increase contractility
2) Dopaminergics: D2 receptors
3) Benzamides: Stimulate ACh release from myenteric neurons
4) Macrolides (Erythrmoycin): Activates motilin receptors, improving gastric emptying in acute situations.