Treatment of GERD:

Question 1

What are the 2 strategies to treating GERD?

Answer 1

1. Reduce Acid Secretions

2. Work on the mechanics of GERD itself (acid splashing up the esophagus from the stomach- dysfunctional valve)

Question 2

The Mechanics of GERD:

Answer 2

• Transient lower esophageal relaxation (TLESR)
• The sphincter at the base of the esophagus relaxes instead of constricts, allowing for retrograde acid reflux flow up to the esophagus from the stomach.

Question 3

What is a ProKinetic Drug?

Answer 3

Promotes Movement

Question 4

Metoclopramide:

Answer 4

D2 Antagonist

• Increase lower esophageal sphincter tone
• Increases peristalsis and gastric emptying
• Inhibits the chemoreceptor trigger zone (useful as an anti- nauseant)

Side Effects:
-Related to D2 antagonism inside and outside the CNS (Pseudo-Parkinsonism) and (Hyperprolactemia- DA usually inhibits PRL release)

Question 5

Domperidone:

Answer 5

D2 Antagonist

-Works outside of the CNS, therefore minimizes movement disorder risk.

Question 6

What is one of the benefits of Prokinetics?

Answer 6

• Can be used to stimulate peristalsis in cases of gastroparesis (loss of gastric motility)
• Can occur due to nerve damage or critical illness.

Question 7

Erythromycin:

Answer 7

• Motilin Agonist
• -Antibiotic well known to cause GI upset.
• Stimulates peristalsis by stimulating the motilin receptor (can therefore use this side effect of the antibiotic to increase GI motility)

Adverse Effect- Possible diarrhea

Question 8

Prucalopride:

Answer 8

5-HT4 Agonist

• Stimulates 5-HT4 receptors (Like Cisapride which was withdrawn)– (causing dangerous arrhythmias)
• Cisapride bound to too many target receptors, where Prucaloride is 5-HT4 selective.
• Caused increased peristalsis.

Adverse Effects:
-Nausea, diarrhea & abdominal cramps.

Question 9

What is one of the most common adverse effects of Opioid Therapy?

Answer 9

Diarrhea

Question 10

Loperamide (Imodium):

Answer 10

Opioid (Mu) Agonist
-Decreases peristalsis
(Works similarly to morphine, decreasing the activity of the myenteric plexus, which decreases the tone of the longitudinal and circular smooth muscles of the intestinal wall)

Side Effects include Constipation and arrhythmia at very high concentrations.

Question 11

Why does Loperamide (Imodium) have minimal CNS mu- agonist side effects? (Including Euphoria, sedation, ect.)

Answer 11

• Loperamide has limited ability to cross the BBB (due to efflux action of P-glycoprotein)
• At recommend doses, it has minimal distribution to the CNS

Question 12

What is the main treatment of Constipation?

Answer 12

Laxatives

–Includes Bulk Osmotic, Stimulant, Softeners, Opioid Antagonists & Others

Question 13

Fibre (Psyllium):

Answer 13

• Bulk Laxative
• Pulls H2O into the stool, increasing bulk and inducing peristalsis
• -Patients should ensure adequate fluid intake to prevent impaction.

Adverse Effects include Bloating and Gas

Question 14

Polyethylene Glycol (sugars) & Magnesium Hydroxide (salts):

Answer 14

Osmotic Laxatives
-Pulls H20 into the colon, increasing bulk and inducing peristalsis.

Adverse Effects include:
Both: Diarrhea
Sugars: Bloating & Gas
Salts: Electrolyte imbalances

Question 15

Bisacodyl & Sennosides:

Answer 15

• Stimulants
• Directly stimulate the colon increasing peristalsis.

Adverse Effects include diarrhea and cramping

Question 16

Docusate:

Answer 16

Stool softeners- emollient effect (enhancing secretion or of interstitial fluids into the stool)

Adverse Effects:
-Mild GI Cramping
However, “all mush & no push” is a common problem.

Question 17

Methylnaltrexone:

Answer 17

Like Naltrexone, but Polar so it does not cross the BBB.

• Blocks peripheral opioid receptors so there is no analgesic effects.
• Very expensive ($$$)

Adverse Effects include diarrhea, nausea and cramping.

Question 18

Prucalopride for Constipation:

Answer 18

• Newer Laxative (also used to treat GERD)
• 5-HT4 Agonist
• Increases peristalsis

Side Effects include nausea, diarrhea and abdominal cramps.

Question 19

Linaclotide:

Answer 19

cGMP agonist

• Intestinal secretagogue (increases intestinal secretions)
• Reduces the transmission of pain signals (analgesic)
• Very Expensive ($$$)

Adverse Effects include diarrhea.