Prokinetics

Question 1

What are the mechanisms of abnormal GI motility

Answer 1

Shock

Surgery

Inflammatory Cytokines

Medications: Opiods

Electrolyte Imbalance –> Hypokalemia, hyponatremia, hypomagnesemia

Dehydration / Hypovolemia

Hypervolemia –> bowel edema

Question 2

What is Hypermotility?

Answer 2

– Hypermotility
• Increased delivery to small intestine –> increased
absorption

• Decreased time for absorption in small bowel

Question 3

What is Hypomotility?

Answer 3

• Decreased delivery to small intestine –> decreased
absorption

Question 4

What are the most common indication for prokinetics?

Answer 4

Indications:
– Increased gastric residual volume
– Gastroparesis

Question 5

What is the MOA of Metoclopramide?

Answer 5

Mechanism of action

• Antagonist of dopamine (D1,D2 receptors)
  
  • Enhances anticholinergic activity (sensitizes GI system to acetylcholine) and GI peristalsis through negative feedback
• Indirect and direct effects on cholinergic receptors – Mixed 5-HT3 antagonist and 5-HT4 agonist
• PROKINETIC EFFECT IS LIMITED TO THE STOMACH

Question 6

would Metoclopramide work on lower GI issues?

Answer 6

no.

Question 7

How is metoclopramide cleared?

Answer 7

adjust dose based on renal and hepatic dysfunction

** heavily renally cleared

Question 8

Motoclopromide notable side effects

when do you avoid use?

Answer 8

Question 9

Erythromycin MOA

Answer 9

Question 10

What are the adverse effect of Erythromycin?

Answer 10

• Qtc prolongation –> big deal, drug and dose related
• Arrythmias
• Skin reactions! –> Stevens Johnson
• Toxic epidermal
• C. diff
• INHIBITS CYP ENZYME SYSTEM

Question 11

What would combination therapy cause?

Answer 11

diarhhea

Question 12

Why would you avoid Azithromycin?

Answer 12

consider avoiding to induction of bacterial resistance

Question 13

MOA of Naloxone

Answer 13

• nonselective Mu opioid receptor antagonist in brain and peripheral tissues

-

• Use as adjunct therapy if no bowel movement after ~3 days with
conventional laxatives

Question 14

MOA: Methylnaltrexone

How do you adjust it?

Answer 14

• Peripherally acting opioid antagonist with

limiting crossing blood brain barrier

WEIGHT BASED TYPE OF A DRUG AND IT IS RENALLY CLEARED

Question 15

MOA: Alvimopan

Answer 15

first drug that reduces post-op ileus

• Peripheral opioid antagonist with limiting the crossing of blood brain barrier
• FDA labeled indication: postoperative ileus
  
  • Accelerate time to upper and lower GI recovery after surgery including small bowel resection with primary anastamosis
• Only agent shown to decrease incidence of ileus and hospital length of stay
  
  • Colorectal surgery and cystectomy patients not on chronic opioids

Question 16

Alvimopan safety issue

Answer 16

MI

• first dose preOp then can maximum 7 days after surgery

Dosing

• 12 mg oral x1, then 12 mg oral twice daily
• Administer first dose 5 h prior to surgery, then maximum 7 days after surgery or until discharge from hospital (whichever is earlier) Max total treatment 15 doses

Question 17

MOA: Neostigmine

Answer 17

Reversible acetylcholinesterase inhibitor that stimulates M2
type receptors on GI smooth muscle cell

Question 18

What complications can you have from Neostigmine?

Wat are the contraindication?

Answer 18

• Complications: bowel ischemia, perforation (usually of cecum) – Response rates 60-90%
• Contraindications
  
  • – Toxic megacolon
    – Mechanical obstruction

Question 19

What are the adverse effects of Neostigmine?

What do you monitor?

What are the contraindication?

Answer 19

• Bradycardia, hypotension, nausea, vomiting, abdominal cramping, increased bronchotracheal secretions
• Monitoring
  
  • Cardiovascular monitoring needed
  • Glycopyrrolate or atropine should be available