Final GI

Question 1

5-HT₃ Receptor Antagonists: Agents

Answer 1

Palonosetron 5-HT_3A CYP3A4

Dolasetron 5-HT_3B CYP3A4

Granisetron 5-HT_3A, 5-HT_3B, 5-HT_3C CYP3A4

Ondansetron 5-HT_3B, 5-HT_1B, 5-HT_1C CYP3A4

Please Don’t Grow Old

-setron

Question 2

5-HT₃ Receptor Antagonists: MOA

Answer 2

MOA: Selective

Central blockade of CTZ and vomiting center

Peripheral Blockade on intestinal vagal and spinal afferent nerves-> drives antiemetic benefit

No affinity for H₁, M₁, or D₂ receptor

Ondansetron, Granisetron, Dolasetron, Palonosetron**

Equal efficacy at equipotent doses

Palonosetron has longer t1/2 = 40 Hrs greater binding affinity (IV)

Cornerstone for chemotherapy-induced N/V

Question 3

5-HT3 Receptor Antagonists: ADEs

Answer 3

Generally well tolerated

HA, Dizziness, Constipation

Small but statistically significant prolongation of the QTc interval

Primarily by K+ channel blockade

-Check for what medications?

Least common with Palonosetron

Serotonin Syndrome (rare)

What meds?

Question 4

Dopamine (D₂) Receptor Antagonists: Agents

Answer 4

Prochlorperazine / Promethazine D₂, M₁, H₁, a-Adrenergic

Olanzapine D₂, 5-HT_1c, 5-HT₃,

Trimethobenzamide D₂, H₁ (weak)

Metoclopramide D₂, 5-HT₃ (weak)

Prokinetic action-> also used for gastroparesis

ADEs: Dystonia, akathisia, parkinsonian, sedation, hyperprolactinemia, hypotension, dry mouth, etc.

Question 5

Neurokinin-1 (NK₁) Receptor Antagonists: MOA

Answer 5

MOA: Central blockade of the NK₁ receptors in CTZ

Blocks binding of substance P

Aprepitant, Netupitant, Rolapitant** (PO)**

Netupitant & Rolapitant t1/2= 90&180 HRs respectively

Netupitant/Palonosetron (Akynzeo)

Fosaprepitant** (IV)**

Converted to aprepitant 30 minutes after infusion

Used for prevention of CINV along with 5-HT₃ antagonists and corticosteroids

Question 6

Neurokinin-1 (NK1) Receptor Antagonists: ADEs

Answer 6

Well tolerated

Fatigue, dizziness

CYP 3A4 substrate and inhibitor

Concomitant use of CYP 3A4 inhibitors can cause toxicity

Aprepitant + Warfarin = decreased INR (Leads to clotting)

Question 7

MISC Anti-emetics

Answer 7

Antihistamines and antimuscarinic drugs

Dimenhydrinate, diphenhydramine, meclizine, etc

-H₁ > M₁

Scopolamine (patch)

-M₁ > H₁

Ginger - 5-HT₃ antagonism

Mirtazapine - 5-HT₃ antagonism, H₁ antagonism

Cannabinoids (CIII)

Dronabinol

Nabilone

-THC reduces vomiting by binding to CB1 receptors

Use for refractory N/V induced by Chemotherapy

Question 8

Constipation defined

Answer 8

A decrease in frequency of fecal elimination characterized by the difficult passage of hard, dry stools

PTs will commonly report the following signs and symptoms of constipation:

Straining to pass stool

The passage of hard, dry stool

Feelings of incomplete evacuation

Passage of small stools

Bloating

Decreased Stool frequency

Question 9

Anti-constipation overview

Answer 9

Watery evacuation within 1-6 hours

Magnesium citrate, hydroxide & sulfate (high-dose)

Sodium phosphates

Bisacodyl (rectal)

Semi-fluid stool in 6-12 hours

Bisacodyl (oral)

Senna

Magnesium sulfate (high dose)

Softening of feces in 1-3 days

Bulk-forming agents

Emollients

PEG 3350

Mineral oil

Question 10

OTC Laxatives - Bulk Forming

Answer 10

MOA: Dissolves or swells in the intestinal fluid, forming emollient gels that facilitate the passage of intestinal contents and stimulate peristalsis

OTC products:

Methylcellulose

Polycarbophil

Psyllium

DOC for constipation, good for PTs on low fiber diet

Question 11

OTC Laxatives: Emollients

Answer 11

MOA: Increases the wetting efficacy of intestinal fluid and facilitate a mixture of aqueous and fatty substances to soften fecal mass

OTC product:​ Docusate sodium

Good for PTs with c/o dry stools, straining when defecating

Question 12

OTC Laxatives: Lubricants

Answer 12

MOA: Soften fecal contents by coating them, thereby preventing colonic reabsorption of fecal water

OTC Products: Mineral oil

Saftey concern of lipid pneumonia

Question 13

OTC Laxatives: Saline Laxatives

Answer 13

MOA: Draws water into the intestine, increasing intraluminal pressure, which acts as a stimulus to increase intestinal motility

OTC products:

Magnesium citrate

Magnesium hydroxide

Sodium phosphate/diphosphate

Screen elders and those with renal and cardiac disease

Question 14

OTC Laxatives: Hyperosmotic Laxatives

Answer 14

MOA: Draws water into rectum to stimulate a bowel movement

OTC Products: Glycerine, Polyethylene Glycol 3350

-Take with 4-8 ounces of water

Question 15

OTC Laxatives: Stimulant Laxatives

Answer 15

MOA: Increase the propulsive peristaltic activity of the intestine by local irritation of the mucosa. Stimulates the secretion of water and electrolytes in the large intestine

OTC products:

Senna

Bisacodyl

-Can cause electrolyte and fluid deficiencies along with malabsorption

Question 16

Laxative Abuse

Answer 16

Utilized for weight loss

Rush food through the GI tract before absorption

Mainly-> loss of water, electrolytes, and minerals

Na+, K+, Mg+, and PO₄

Tremors, weakness, blurry vision, fainting, kidney injury, metabolic alkalosis or arrythmias

Abuse may lead to dependence

Chronic abuse may cause “lazy” colon infection, INC risk of colon cancer

When to suspect

More common in women, eating disorders, PMH inconsistency, altered diarrhea constipation complaints