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TitleAcing the GI Board Exam.
Author
LanguageEnglish
File Size14.3 MB
Total Pages275
Table of Contents
                            Cover
Front Matter
Contents
Chapter 1
Chapter 2
Chapter 3
Chapter 4
Chapter 5
Appendix A
Appendix B
Bibliography
Subject Index
                        
Document Text Contents
Page 2

14-0960_Spiegel GI Board Exam 2E_TitleGraphic.eps


THE ULTIMATE CRUNC RESOURCE

Page 137

118 Chapter 3

Vignettes 77-85: Motility Meds Mix n’ Match

On the left is a list of medications used in patients with neurogastrointestinal and motility

disorders. On the right is a list of mechanisms of action. Match each medication on the left to its

corresponding mechanism of action on the right.

77. Linaclotide

78. Alosetron

79. Erythromycin

80. Rifaximin

81. Lubiprostone

82. Peppermint oil

83. Alvimopan

84. Baclofen

85. Methylnaltrexone

Inhibits TLESRs

Smooth muscle relaxant/antispasmodic

Chloride channel-2 agonist

Peripheral acting μ opioid antagonist

5-HT3 receptor antagonist

Motilin receptor agonist

Guanylate cyclase C agonist

Minimally absorbed antibiotic

Page 138

14-0960_Spiegel GI Board Exam 2E_TitleGraphic.eps


“Tough Stuff” Vignettes 119

Vignettes 77-85: Answers

Neurogastroenterology and motility disorders comprise the most common set of conditions

managed by gastroenterologists. This question bank asks about mechanisms of actions of thera-

pies used for these conditions. I briefly discuss each medication, including its clinical use and

pharmacological mechanism.

77. Linaclotide: Linaclotide is a first-in-class guanylate cyclase C (GCC) receptor agonist. The

FDA approved linaclotide for treatment of chronic idiopathic constipation and irritable

bowel syndrome with constipation (IBS-C). By activating the GCC receptor, linaclotide

increases the intracellular availability of cyclic GMP in enterocytes. This, in turn, activates

various ion channels, including the CFTR chloride channel, which pumps chloride into

the lumen of the bowel. To maintain electrical neutrality, cations like sodium will follow,

and water will follow in its wake. The result is a net transfer of water into the lumen. In

light of this mechanism of action, linaclotide is associated with diarrhea, which is some-

times okay for patients suffering from severe constipation, but can also be dose limiting.

Diarrhea is reported to occur in about 20% of patients. In addition, linaclotide is thought

to reduce firing of the afferent nerves in the myenteric plexus. This may account for some

of linaclotide’s established benefits for abdominal pain in IBS. The therapy is specifically

approved for the pain of IBS based on the FDA label. Based on phase III clinical trials

of linaclotide at a dose of 290 mcg once daily, the effect size in IBS is substantial, with a

number needed to treat (NNT) of 5 (see Vignette 5 if you need a reminder about how to

calculate the NNT).

78. Alosetron: Alosetron is a first-in-class 5-HT3 receptor antagonist. It was originally

approved for wide use in patients with diarrhea-predominant IBS (IBS-D), but was subse-

quently withdrawn from the market because of concerns about ischemic colitis and severe

obstipation. Subsequent analyses found that ischemic colitis was quite rare, occurring in

about 3 per 1000 patients, and when it occurred it was generally mild in severity. Because

the treatment is highly effective in IBS-D at a dose of 0.5 mg twice daily, with an NNT

of 8 based on meta-analysis of randomized trials, the treatment was eventually brought

back on the market under a restrictive use program. The FDA only approves alosetron for

women with severe IBS who have failed typical first-line treatments.

Linaclotide is a guanylate cyclase C receptor agonist.

Here’s the Point!

Alosetron is a 5-HT3 receptor antagonist.

Here’s the Point!

Page 274

Subject Index 255

Sitzmark study Vignette 30

somatostatin Vignettes 37-41

sphincter, upper esophageal Vignette 7

spider angiomata Vignette 6

sprue, celiac Vignette 163

sprue, tropical Vignettes 63, 162

steatosis, microvesicular Vignette 71

steroids, anabolic Vignette 52

stomatitis, angular Vignette 19

sumatriptan, ischemic colitis due to Vignette 74

swallowing bleach Vignette 171

systemic lupus erythematosus (SLE) Vignette 18

systemic sclerosis Vignette 114

temperature-pulse dissociation Vignettes 2, 135

tetracycline Vignette 63

tetracycline, microvesicular steatosis from Vignette 75

thatched roof hut Vignette 109

thumbprinting Vignette 42

transient lower esophageal sphincter relaxation Vignette 22

transplantation, bone marrow Vignette 43

trichilemmoma Vignette 49

triglycerides Vignette 125

triglycerides, medium chain Vignettes 136, 137

trimethoprim-sulfamethoxazole Vignette 94

Tropheryma whipplei Vignette 64

tuberculosis, gastrointestinal Vignette 91

tuberous sclerosis Vignettes 31, 157

tumor, neuroendocrine Vignette 19

Turcot’s syndrome Vignette 158

2x2 diagnostic contingency table Vignette 133

tylosis Vignette 29

typhoid fever Vignette 135

ulceration, aphthous Vignette 21

ulceration, flask-shaped Vignette 90

ulceration, genital Vignette 21

ursodeoxycholic acid (UDCA) Vignette 134

uveitis, anterior Vignette 21

uvula, snapping Vignette 7

valproic acid, microvesicular steatosis from Vignette 71

vasculitis, leukocytoclastic Vignette 48

veno-occulsive disease (VOD) Vignette 43

Vibrio parahemolyticus Vignette 53

Vibrio vulnificus Vignettes 53, 59

villous atrophy Vignettes 161-165

vimentin staining Vignette 105

vitamin A, microvesicular steatosis from Vignette 75

Page 275

256 Subject Index

vomiting Vignette 10

von Hippel-Lindau disease Vignette 31

Weil’s syndrome Vignette 2

Whipple’s disease Vignettes 34, 64

Wilson’s disease Vignette 31

xanthelasma Vignette 20

zidovudine, microvesicular steatosis from Vignette 75

zinc deficiency Vignettes 15, 121

Zollinger-Ellison syndrome Vignettes 33, 37, 165

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