Module 2: Gastric Protectants Flashcards
What are two examples (other than H2 receptor antagonists, D2 receptor antagonists, antacids and PPI’s) that are used as gastric protectants?
Misoprostol
Sucralfate
What are GI indications for misoprostol?
Tx and prevention of NSAID induced gastroduodenal ulcers
Tx of duodenal ulcers caused by PUD
What are GI indications for sucralfate?
Suppress H. Pylori and inhibit acid secretion in infected patients with duodenal ulcers.
Note: not used in treatment of peptic ulcers as PPI’s more effective.
As such, sucralfate used in the initial management of GERD in pregnancy.
What is the MOA for misoprostol?
- Synthetic analogue of prostaglandin E1
- is rapidly de-esterified to misoprostol acid in the stomach upon oral administration.
- The active metabolite then binds to specific prostaglandin receptors on the gastric parietal cells thus inhibiting acid production.
- May increase mucus production, increase bicarbonate secretion in the duodenum, increase mucosal blood flow, decrease vascular permeability, increase prostaglandins that have been depleted d/t various insults in the area.
What is the MOA for sucralfate?
- it is a sulfated polysaccharide, sucrose octasulfate, complexed with aluminum hydroxide.
- prevents acute, chemically-induced mucosal damage and heals chronic ulcers without altering gastric acid or pepsin secretion or significantly buffering acid
- sucralfate stimulates angiogenesis and the formation of granulation tissue, possibly due to growth factor binding
- also binds to the injured tissue, thereby delivering growth factors and reducing access to pepsin and acid
What are the pharmacokinetic considerations for misoprostol?
A: Misoprostol, an ester, undergoes rapid de-esterification to its pharmacologically active metabolite, misoprostol acid, in the stomach after oral administration. Absorption of misoprostol acid is rapid, with peak plasma concentrations occurring within 15 to 30 mins and rapidly declining within 120 mins. Only 7% of the dose is systemically bioavailable as the acid following oral administration. Misoprostol acid does not accumulate when misoprostol is taken chronically
D: Approx 85% of misoprostol acid is bound to serum albumin.
M: Misoprostol acid is metabolized by the liver but it does not inhibit or induce the hepatic CYP 450 system.
E: Inactive metabolites are mostly excreted in the urine with a minor proportion found in fecal excretions. The plasma half-life of misoprostol acid is 13-40 mins. Plasma steady state is achieved within 2 days.
Is misoprostol safe for pregnancy and lactation?
Pregnancy: Misoprostol is a potent uterine stimulant that induces abortion in early pregnancy, and labour in advanced pregnancy. Premature labor or birth defects can also result when misoprostol is administered to pregnant women.
Lactation: No studies to evaluate the passage of misoprostol or its active metabolite, misoprostol acid, into breast milk. There is a potential for drug-induced diarrhea in the infant.
Is misoprostol safe in pediatrics?
Safety and efficacy below 18 yrs not studied.
Is sucralfate safe in pregnancy and lactation?
As it is virtually unabsorbed orally, it is indicated for initial tx of GERD in pregnancy.
Most authorities consider it safe during breastfeeding.
Is surcralfate safe in pediatrics?
Not established.
What are some common expected side effects of misoprostol?
Headache
Abd pain, mild-dose related diarrhea
Vaginal bleeding and uterine cramping
What are adverse effects of sucralfate?
few adverse effects.
It can bind to other drugs if taken simultaneously.
Similar to antacids, significant aluminum retention only occurs in patients with renal failure
Sucralfate can also bind to phosphate and lead to hypophosphatemia. Combining sucralfate and antacids can potentially amplify these effects
What are significant drug interactions with misoprostol?
Antacids decreased bioavailability of misoprostol. Magnesium-containing antacids may increase risk for misoprostol-induced diarrhea.
Oxytocin = enhanced therapeutic effect of oxytocin.
What are the pharmacokinetics of sucralfate?
A: Minimal from GI tract
D: Acts locally at ulcer sites; unbound in GI tract to aluminum and sucrose octasulfate
M: None
E: Primarily urine (small amounts of sulfated disaccharide)
Contraindications for misoprostol?
Pt’s who are hypersensitive to misoprostol or any of its ingredients
Pregnant women
Women of childbearing potential unless the possibility of pregnancy has been excluded and an effective method of contraception started
What are some disease related concerns to consider with sucralfate?
Diabetes: Hyperglycemia
Renal impairment: use with caution as contains aluminum and inadequate excretion can cause build-up.
What is the onset, peak, duration and half-life of misoprostol?
Onset = inhibition of gastric secretion 30 mins
Peak = in fasting state 12 (give or take 3) mins
Duration = 3 hours
Half-life: 20-40 mins
What is the onset, duration, peak and half-life for sucralfate?
Onset = 1-2 hour acid neutralizing capacity
Other’s unkown.
