GI pharm – HY mixed agents

a) D2 receptor antagonist.

b) Diabetic gastroparesis (stimulates peristalsis); anti-emetic

c) Hyperprolactinemia; QT prolongation; tardive dyskinesia (extra-pyramidal side-effects)

a) Trial of PPIs or H2 blockers.

b) Metoclopramide, followed by erythromycin; wrong answer = omeprazole (PPI).

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GERD vs diabetic gastroparesis (this subsection is also in the antacid post because of the yieldness):

• Diagnosis of GERD is done with 2-week trial of PPIs or H2-blockers. PPIs are classically chosen for the 2-week trial, but one of the 2CK NBME Qs has trial of H2 blockers as an answer (and PPIs not listed). Both are correct answers. If you’re forced to choose between the two, however, choose the PPI, as mentioned above.
  • 55M + burning sensation in throat after meals past three months + otherwise healthy and no cardiovascular issues; next best step in pharmacologic therapy? –> answer = trial of PPIs or H2 blockers.
• Don’t confuse with diabetic gastroparesis, which can present like GERD, but in someone who has bad diabetes. USMLE will slam you on this.
  • 55M + burning sensation in throat after meals past three months + T2DM + HbA1c of 9.6 + lack of pinpoint discrimination up to the ankles; next best step in pharmacologic therapy? –> answer = metoclopramide; wrong answer = omeprazole.
  • If the patient has poor glycemic control and neuropathy, the latter extends to the nerves innervating the GI tract as well –> can present as diarrhea/constipation or GERD-like symptoms.
  • First step is endoscopy to rule out physical obstruction. If negative, then do gastric-emptying scintigraphy (scintigraphic gastric-emptying assay) to confirm delayed gastric emptying. First step in treatment is smaller meals. If insufficient, start using metoclopramide (D2 antagonist), which is a pro-kinetic agent (stimulates peristalsis) and anti-emetic; after metoclopramide, can also use erythromycin (macrolide antibiotic that is also a motilin-receptor agonist).
  • Bottom line is:
    • GERD-like Sx in someone without diabetes, answer = GERD; do trial of PPIs or H2 blocker.
    • GERD-like Sx in someone with bad diabetes; answer = diabetic gastroparesis; do metoclopramide, followed by erythromycin.

a) Mu-opioid receptor agonist.

b) Used for diarrhea (i.e., promotes constipation).

c) Low addictive potential

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Loperamide

• Mu-opioid agonist used as an anti-diarrheal agent (i.e., promotes constipation).
• Low addiction potential –> USMLE will, weirdly enough, make this into a “plus sign question,” where there are varying numbers of (+), and the answer is “++++” for  mu-agonism, and only “+” for addictive potential; in contrast, meperidine is a highly addictive opioid, with “++++” for addictive potential.

a) Acts as an NSAID.

b) Used for IBD.

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Sulfasalazine

MOA of sulfasalazine?

• Combination of sulfapyridine (an antibiotic) and 5-ASA (5-aminosalicylic acid; aka mesalamine).
• Used for inflammatory bowel disease (IBD; i.e., ulcerative colitis and Crohn).
• USMLE just wants you to know that sulfasalazine = 5-ASA = mesalamine = NSAID. Don’t worry about the sulfapyridine.
• Sulfasalazine and mesalamine are interchangeable on the USMLE.
• Sometimes Qbanks will get pedantic about when to use NSAID vs steroids for IBD; the USMLE won’t. You will not see both an NSAID and steroid as answers to the same question, where you have to pick between the two. And if you did, the vignette would give you, e.g., renal failure or peptic ulcers, where NSAIDs would be contraindicated anyway.

a) Somatostatin analogue

b) Acute variceal bleeds; also used for acromegaly, VIPoma, and carcinoid syndrome.

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Octreotide

MOA of octreotide?

• Somatostatin analogue.
• Longer half-life than endogenous somatostatin.
• Somatostatin is a hormone that generally shuts off the action of many endocrine hormones, notably growth hormone. Think of it as a general endocrine suppressor. –> “Somatostatin…oh right, that’s the one that shuts off other hormones, right?”

When is octreotide the answer?

• Highest yield –> pharmacologic treatment for bleeding esophageal varices.
  • Acutely bleeding varices treatment = rubber banding + octreotide.
  • Varices bleeding prophylaxis = propranolol (beta-blockade).
• Can also be used for acromegaly, VIPoma, and carcinoid syndrome (remember: somatostatin shuts off hormones, so this makes sense right?).

a)

• 5-HT3 (serotonin) receptor antagonist.
• 5-HT3 receptors are located at the chemoreceptor trigger zone (vomiting center) in the caudal (lower) medulla. If the USMLE question shows you a sagittal brain MRI and asks about ondansetron MOA, choose the caudal medulla letter as the answer.

b)

• Very strong anti-emetic (stronger than metoclopramide).
• Used mostly in patients undergoing chemotherapy who have nausea and vomiting.

c)

• QT prolongation (HY, along with metoclopramide, macrolides, TCAs, and anti-psychotics).

a)

• Blocks NK1 receptors.
• Substance P normally binds to NK1 receptors to induce pain and nausea.
• Therefore aprepitant antagonizes the effect of Substance P.
• NK1 = neurokinin-1, aka tachykinin.

b)

• Similar to ondansetron, can be used for nausea and vomiting in patients undergoing chemotherapy (stronger than metoclopramide).

a)

• Pancreatic lipase inhibitor (i.e, prevents breakdown of fats in lumen of small bowel –> decreased absorption).

b)

• Can be used for obesity.
• Usually a distractor, rather than correct answer, on USMLE questions. But because it shows up in answer choices, students frequently say, “What’s that?”

c)

• Can cause steatorrhea and fat-soluble vitamin deficiency in theory.

a)

• Pancreatic enzyme replacement composed of amylase, lipase, and proteases.

b)

• Given to patients with chronic pancreatitis (i.e., pancreas burnout from multiple bouts of acute pancreatitis, usually in the setting of alcoholism).

What’s a notable point about the presentation of patients with chronic pancreatitis?

• USMLE vignette will give an alcoholic with Hx of multiple acute pancreatitis episodes who has steatorrhea (i.e., unable to absorb fats because he lacks pancreatic lipases) + the Q will say amylase and lipsase levels are low or normal (chronic pancreatitis is characterized by organ burnout, not acute elevations in enzymes).
• (Tangentially, if you get a vignette of hepatic cirrhosis, ALT and AST will be low, not high, because the liver is burned out).

Metoclopramide –> D2 receptor antagonist (used for general nausea; also for hyperemesis gravidarum).

Ondansetron –> 5HT3 (serotonin) receptor antagonist (used in chemotherapy patients).

Aprepitant –> NK1 receptor antagonist, thereby antagonizing the effects of Substance P (used in chemotherapy patients).

a) Octreotide

b) Used for acute esophageal varices bleeding, acromegaly, VIPoma, carcinoid syndrome.

Loperamide

• Mu-opioid agonist used as an anti-diarrheal agent (i.e., promotes constipation).
• Low addiction potential –> USMLE will, weirdly enough, make this into a “plus sign question,” where there are varying numbers of (+), and the answer is “++++” for  mu-agonism, and only “+” for addictive potential; in contrast, meperidine is a highly addictive opioid, with “++++” for addictive potential.

Orlistat

MOA of orlistat?

• Pancreatic lipase inhibitor (i.e, prevents breakdown of fats in lumen of small bowel –> decreased absorption).

When is it used?

• Can be used for obesity.
• Usually a distractor, rather than correct answer, on USMLE questions. But because it shows up in answer choices, students frequently say, “What’s that?”

Adverse-effects of orlistat?

• Can cause steatorrhea and fat-soluble vitamin deficiency in theory.