Treatment / Replace PGs
Replace prostaglandins
MISOPROSTOL
| Based on mechanism of action, MISOPROSTOL (PGE1) is the drug of choice for treatment of ulcers induced by nonsteroidal anti-inflammatory agents, although side effects and the need for frequent dosing limit its use. It is abortifacient. |  |
- approximately 15-20% of patients with arthritis develop ulcers
- incidence is increasing as the mean age of the population increases
Mechanism of Action
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MISOPROSTOL locally blocks the action of the NSAIDs on the stomach lining, leaving the NSAIDs free to act systemically at their target site
- there are two reasons that this does, in fact, happen:
- PGE1 is less involved in inflammation than other prostaglandins but more involved in acid, mucous and bicarbonate production
i.e. a pharmacodynamic interaction - MISOPROSTOL is absorbed and functions systemically, but it has a shorter half-life (30-40 minutes) than some NSAIDs: acetaminophen and ibuprofen (2 hours), rofecoxib (17 hours), but not aspirin (15 minutes)
i.e. a pharmacokinetic interaction
- PGE1 is less involved in inflammation than other prostaglandins but more involved in acid, mucous and bicarbonate production
- there are two reasons that this does, in fact, happen:
- reduces histamine-stimulated cAMP production à decreases acid secretion AND stimulates of mucous and bicarbonate secretion i.e., both raises gastric pH and protects surface
- reduces incidence of NSAID-induced ulcers to <3% and the incidence of ulcer complications by 50%
Pharmacokinetics
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rapidly absorbed and metabolized to the active free acid
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short serum half-life (<30 minutes)
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excreted in urine
- available in a combined formulation with an NSAID (diclofenac) specifically for the treatment of NSAID-induced ulcers
Side Effects
- not widely used due to side effects and need for multiple daily dosing
- dose related diarrhea, severe nausea and cramping abdominal pain (due to increased intestinal electrolyte and fluid secretion) in 10-20% of patients
- stimulates uterine contractions à ABSOLUTELY CONTRAINDICATED DURING PREGNANCY