Pharmacology for Upper GI Disorders

Question 1

Sucralfate is…

Answer 1

A mucosal protection agent.

Question 2

H2 receptor antagonists

Answer 2

1. Rapidly absorbed from GI tract
2. Peak serum levels reached in 2 hrs
3. Only small % is protein bound
4. Up to ~35% is metabolized by liver
5. Excreted by kidney via glomerular filtration and tubular secretion; competes with creatinine for excretion
6. Crosses BBB
7. Examples include cimetidine, ranitidine, famotidine, nizatidine

Question 3

Adverse effects of cimetidine

Answer 3

Cytochrome P450 inhibitor associated with:

1. Gynecomastia in men
2. Decreased sperm count
3. Galactorrhea in women
4. Very rarely causes bradycardia or heart block
5. Suppresses T lymphocytes and so is avoided after organ transplant

Question 4

PPIs

Answer 4

1. Pro-drugs activated only in the acidic milieu of the secretory canaliculi
2. Permanently inactivate H+/K+ ATPase molecules, so even after drug is discontinued, return of acid secretion must await synthesis of new pump
3. Once-daily dosing is typical
4. Should be taken just before first meal of day
5. Metabolized by cytochrome P450 system, so may decrease clearance of warfarin, anti-epileptic drugs, and benzodiazepines
6. Produces hypergastrinemia in 5-10% of pts

Question 5

Regimens for eradication of H. pylori infection

Answer 5

1. PPI + clarithromycin + amoxicillin OR
2. PPI + clarithromycin + metronidazole OR
3. PPI + bismuth subsalicylate + metronidazole + tetracycline

Question 6

Causes of gastroparesis

Answer 6

1. Diabetes mellitus – autonomic neuropathy
2. Hypothyroidism
3. Scleroderma
4. Amyloidosis
5. Familial
6. Idiopathic
7. Neurological causes
8. Acute infection (e.g., Norwalk virus, Rubella, CMV, EBV, Lyme disease)
9. Drugs – anticholinergics, opiates, TCAs
10. Paraneoplastic syndrome

Question 7

Metoclopramide

Answer 7

1. Used to treat gastroparesis and associated emesis
2. Antagonizes central and peripheral dopamine receptors
3. Augments ACh release from postganglionic neurons
4. Sensitizes muscarinic receptors on smooth muscle cells to ACh
5. Side effects: extrapyramidal disorders, hyperprolactinemia

Question 8

Somatostatin

Answer 8

1. Acts on hypothalamus to inhibit release of growth hormone
2. Short half-life
3. Analogs used to treat: VIPoma, carcinoid tumors, pancreatic ascites and pancreatic fistulae, high-output intestinal fistulae, bleeding esophageal varices (reduces splanchnic blood flow)

Question 9

Indications for endoscopy in pts with dyspepsia

Answer 9

1. Age > 50 yrs OR

2. Alarm symptoms (e.g., bleeding, iron deficiency anemia, vomiting, weight loss)