GASTROINTESTINAL SYSTEM
B. Antiulcer/Gastroesophageal Reflux Disease Agents
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PHARMACOLOGY A. Antibleeding Agents
1. Vasopressin (Pitressin; Taketomo, Hodding, &
Kraus, 2015)
a. Action. Vasopressin is a nonselective, short- acting vasoconstrictor. It decreases splanchnic blood flow and portal hypertension.
b. Uses. Used to treat acute massive GI hemorrhage.
c. Dosage. Continuous intravenous (IV) infu- sion. Initial 0.002 to 0.005 units/kg/min; double as needed every 30 minutes to a maximum of 0.01 units/kg/min. If bleeding stops for 12 hours, taper the infusion off over 24 to 48 hours.
d. Side effects include hypertension, brady- cardia, arrhythmias, wheezing, bronchospasm, abdominal cramping, vomiting, water intoxi- cation, decreased urine output, hyponatremia, decreased platelet count, and hemorrhage.
2. Octreotide Acetate (Sandostatin; Taketomo et al., 2015) a. Action. Decreases splanchnic blood flow;
inhibits gastrin synthesis and gastric acid output.
b. Uses. Used to treat GI hemorrhage and intractable diarrhea. This agent has been used for the treatment of chylothorax. Sandostatin is used when conservative treatment fails.
c. Dosage. Administer 1 to 2 mcg/kg IV bolus;
infusion rate 1 to 2 mcg/kg/hr IV for GI hemor- rhage, titrating the rate to response. Continuous IV infusion following a bolus dose of 1 mcg/
kg followed by 1 mcg/kg/hr. Dosage of 1 to 10 mcg/kg every 12 hours (IV, subcutaneous [SC] administration) is used for intractable diar- rhea. Dose reductions are recommended for patients with renal failure.
d. Side effects include bradycardia, chest pain, hypertension, abdominal pain, nausea, diarrhea, headache, fat malabsorption, hypoglycemia or hyperglycemia, hypothyroidism, and possible ana- phylactic shock. The incidence of gallstones and biliary sludge is approximately 33% in children receiving the medication for more than 12 months.
3. Vitamin K1, Phytonadione (AquaMEPHYTON, mephyton; Taketomo et al., 2015)
a. Action. Provides vitamin K activity and can be used as a cofactor in the liver synthesis of clotting factors II, VII, IX, and X; however, the mechanism of stimulation is unknown.
b. Uses. Prevents and treats hypoprothrombin- emia caused by malabsorption, drug- or antico- agulant-induced vitamin K deficiency.
c. Dosage. Note: Dosing presented is for GI- specific diseases for which supplementation is needed and is based on international normalized ratio (INR).
i. Biliary atresia. Infants 1 to 6 months old: INR more than 1.2 to 1.5: 2.5 mg PO QD (orally every day). INR more than 1.5 to 1.8 initial 2 to 5 mg intramuscular (IM) once fol- lowed by 2.5 mg PO once daily. INR more than 1.8 initial 2 to 5 mg IM followed by 5 mg PO once daily.
ii. Cholestasis. Infants, child, and adoles- cents: administer 2.4 to 15 mg/d PO.
iii. Liver disease. Infants, child and adolescents: administer 2.5 to 5 mg/d PO.
d. Side effects include a transient flushing reaction, rare hypotension, hypertension, rare dizziness, rash, and urticaria. U.S. boxed warn- ing: Severe reactions resembling anaphylaxis have occurred during and immediately after IV administration. IV administration should be used when other routes of administration are not feasible and the benefits outweigh the risks.
B. Antiulcer/Gastroesophageal Reflux Disease
elevated serum creatinine, elevated aspartate aminotransferase (AST) and alanine aminotrans- ferase (ALT), neutropenia, pancytopenia, and thrombocytopenia.
e. Additional warnings. The use of H2 blockers and proton-pump inhibitors (PPIs) has been associated with increased incidence of gastro- enteritis and community-acquired pneumonia in children (Stark & Nylund, 2016). In neonates, there is an associated increased incidence of infectious complications and necrotizing entero- colitis (NEC; Slaughter et al., 2016).
2. Ranitidine (Zantac; Slaughter et al., 2016; Stark &
Nylund, 2016; Taketomo et al., 2015)
a. Action. A histamine-2 receptor antagonist that decreases the secretion of acid.
b. Uses. Used for short-term treatment of active peptic ulcer disease, GERD, or long-term pro- phylaxis and prevention of hypersecretory states and bleeding.
c. Dosage. GI bleed or stress ulcer prophylaxis.
Infant: administer 2 to 6 mg/kg daily via IV divided every 8 hours. Child and adolescents: administer 3 to 6 mg/kg daily via IV, divided every 6 hours, for a maximum of 300 mg daily; 0.15 to 0.5 mg/
kg/dose for one dose followed by 0.08 to 0.2 mg/
kg/hr continuous IV infusion. GERD dosing is 5 to 10 mg kg/d divided twice daily; maximum daily dose is 300 mg daily. Dose reduction is recom- mended for patients with renal impairment.
d. Side effects include bradycardia (rapid IV administration), tachycardia, agitation, head- ache, dizziness, nausea, vomiting, elevated serum creatinine, hepatitis, arthralgia, leukope- nia, and thrombocytopenia.
e. Additional warnings. The use of H2 blockers and PPIs has been associated with increased incidence of gastroenteritis and community- acquired pneumonia in children (Stark &
Nylund, 2016). In neonates, there is an associ- ated increased incidence of infectious complica- tions and NEC (Slaughter et al., 2016).
3. Famotidine (Pepcid; Slaughter et al., 2016; Stark &
Nylund, 2016; Taketomo et al., 2015)
a. Action. A histamine-2 receptor antagonist that decreases the secretion of acid.
b. Uses. Used in therapy and treatment of pep- tic ulcer disease, GERD, and hypersecretory states.
c. Dosage. GERD: In infants, administer 0.5 to 1 mg/kg daily PO up to 8 weeks or 0.25 to 0.5 mg/
kg daily via IV. In children and adolescent dosing is 0.25 to 0.5 mg/kg/dose every 12 hours up to 20 mg/dose. Stress ulcer prophylaxis: In infants, children, and adolescents, administer 0.5 to 1 mg/kg/dose every 12 hours, with a maximum dose of 20 mg/dose. Dose reductions are recom- mended for patients with renal impairment.
d. Side effects include arrhythmias, tachycar- dia, headache, dizziness, constipation, diarrhea, thrombocytopenia, and pancytopenia.
e. Additional warnings. The use of H2 blockers and PPIs has been associated with increased incidence of gastroenteritis and community- acquired pneumonia in children (Stark &
Nylund, 2016). In neonates, there is an associated increased incidence of infectious complications and NEC (Slaughter et al., 2016).
4. Omeprazole (Prilosec; Slaughter et al., 2016;
Stark & Nylund, 2016; Taketomo et al., 2015)
a. Action. PPI; direct inhibitor of hydrochloric acid secretions at the cellular level. It demonstrates antimicrobial activity against Helicobacter pylori.
b. Uses. Used for short-term treatment (4−8 weeks) of severe erosive esophagitis and severe GERD and duodenal ulcer disease associated with H. pylori.
c. Dosage. GERD: In infants, administer 0.7 mg/
kg/dose daily PO; for children greater than or equal to 1 year and adolescents 5 kg to less than 10 kg, administer 5 mg Q day PO; 10 kg to less than 20 kg, 10 mg Q day PO; greater than or equal to 20 kg, 20 mg Q day PO; Erosive esophagitis: 5 kg to less than 10 kg, administer 5 mg Q day PO; 10 kg to less than 20 kg, 10 mg Q day PO; greater than or equal to 20 kg, 20 mg Q day PO. H. pylori eradication: administer 1 to 2 mg/kg/d divided into two doses; maximum single dose of 20 mg. The capsule form of the med- ication is a sustained-release capsule. The capsule can be opened and the beads mixed with an acidic medium such as 1 tablespoon of applesauce. The tablets of medication should not be crushed. The manufacturer suggests using the suspension for administration in a nasogastric (NG) tube.
d. Side effects include bradycardia, tachycardia, nausea, diarrhea, abdominal cramps, headache, dizziness, skin rash, elevated liver enzymes, hypomagnesemia, proteinuria, skin rash, and thrombocytopenia.
e. Additional warnings. The use of H2 blockers and PPIs has been associated with increased inci- dence of gastroenteritis and community-acquired
PHARMACOLOGY ■ 539
pneumonia in children (Stark & Nylund, 2016).
In neonates, there is an associated increased incidence of infectious complications and NEC (Slaughter et al., 2016).
5. Pantoprazole (Protonix; Slaughter et al., 2016;
Stark & Nylund, 2016; Taketomo et al., 2015) a. Action. In PPI, pantoprazole is a direct inhib- itor of hydrochloric acid secretions at the cellular level. This PPI more directly inhibits acid secre- tion compared with other PPIs. It demonstrates antimicrobial activity against H. pylori.
b. Uses. Used to treat GERD (Food and Drug Administration [FDA] approved in ages
≥5 years), pathological hypersecretory condi- tions, and as an adjunct to duodenal ulcer treat- ment associated with H. pylori.
c. Dosage. GERD: Infants and children younger than 5 years, administer 1.2 mg/kg/d daily for 4 weeks; children 5 to 11 years, 20 or 40 mg PO daily; children and adolescents, 20 or 40 mg once daily. For gastric acid suppression when PO administration is not appropriate or tolerated, the dose is 0.8 or 1.6 mg IV once daily, maximum dose 80 mg.
d. Side effects include hypotension, hyperten- sion, headache, urticaria, pruritus, hypergly- cemia, hypermagnesemia, nausea, vomiting, diarrhea, constipation, urinary frequency, ele- vated liver enzymes, elevated triglyceride lev- els, cough, and dyspnea. Anaphylaxis has been reported with IV administration.
e. Additional warnings. The use of H2 blockers and PPIs has been associated with increased incidence of gastroenteritis and community- acquired pneumonia in children (Stark &
Nylund, 2016). In neonates, there is an associ- ated increased incidence of infectious complica- tions and NEC (Slaughter et al., 2016).
6. Lansoprazole (FIRST-Lansoprazole; Slaughter et al., 2016; Stark & Nylund, 2016; Taketomo et al., 2015)
a. Action. PPI; acts as a direct inhibitor of hydrochloric acid secretion at the cellular level.
b. Uses. For short-term treatment of symptom- atic GERD (up to 8 weeks; FDA approved for ≥1 year); for duodenal ulcer treatment associated with H. pylori, erosive esophagitis, and hyperse- cretory conditions.
c. Dosage. GERD: Infants 1 to 2 mg/kg/d for weight-based dosing; for fixed dosing in infants older than 3 months, administer 7.5 mg twice a day or 15 mg daily; children 1 to 11 years
who weigh less than or equal to 30 kg, 15 mg daily for up to 12 weeks; children greater than 30 kg, 30 mg daily for up to 12 weeks; children 12 years or older, 15 mg once daily for up to 8 weeks.
d. Side effects include hypertension, hypo- tension, nausea, dyspepsia, abdominal pain, diarrhea, constipation, elevated liver enzymes, dizziness, and headache.
e. Additional warnings. The use of H2 blockers and PPIs has been associated with increased incidence of gastroenteritis and community- acquired pneumonia in children (Stark &
Nylund, 2016). In neonates, there is an associ- ated increased incidence of infectious complica- tions and NEC (Slaughter et al., 2016).
7. Sucralfate (Carafate; Taketomo et al., 2015) a. Action. Gastric protectant; paste formation and ulcer adhesion occur within 1 to 2 hours of administration and last up to 6 hours.
b. Uses. Used for short-term management of duodenal ulcers and gastritis; typically may be used for esophageal, gastric, and rectal erosions.
c. Dosage. Dose is not established; administer 40 to 80 mg/kg/d PO in divided doses every 6 hours. Administer 1 hour before meals or on an empty stomach.
d. Side effects include constipation and rarely, anaphylaxis, bezoar formation, and hypersen- sitivity. Decreased absorption of concurrently administered drugs may occur. Safety and effi- cacy in children have not been established.
8. Calcium Carbonate (Maalox; Taketomo et al., 2015) a. Action. Maalox is an antacid that neutralizes gastric acid.
b. Uses. Provides symptomatic relief for peptic ulcer, gastritis, esophagitis, hiatal hernia, and treatment of hyperphosphatemia in end-stage renal failure.
c. Dosage. In children 2 to 5 years, administer one tablet (400 mg calcium carbonate) as symp- toms occur (not to exceed 3 tablets/d); chil- dren older than 5 years to 11 years, two tablets (800 mg) as symptoms occur (not to exceed 6 tablets/d); children older than 11 years, two to four tablets as symptoms occur (not to exceed 15 tablets/d).
d. Side effects include headache, laxative effect, hypercalcemia, and hypophosphatemia.