Sucralfate

Mechanism

Mechanism of action

In an acidic gastric environment characterized by a pH < 4.0, sucralfate undergoes rapid polymerization and intramolecular cross-linking. The aluminum hydroxide ions dissociate from the complex, leaving a polyanionic macromolecular structure of sulfated sucrose with a strongly negative charge.

This molecule with a high density of negative charge selectively binds, by electrostatic attraction, to the positively charged proteins (albumin, fibrinogen) exposed on the necrotic surface of ulcerative craters. An adherent and insoluble physical viscoelastic barrier is generated that protects the damaged mucosa from the corrosive digestive action of hydrochloric acid (HCl), pepsin and bile salts for more than 6 hours.

Additionally, sucralfate locally stimulates the synthesis of endogenous prostaglandins (PGE₂ and PGI₂) in the gastric mucosa, promotes the physiological secretion of bicarbonate and mucus, stimulates the local release of epidermal growth factor (EGF) and fibroblast growth factor (FGF), and directly adsorbs bile salts and free pepsin in the lumen. stomach.

Pharmacokinetics

Pharmacokinetics

• Absorption: Virtually zero orally (< 5% of the sucrose sulfate component is absorbed systemically). The released aluminum is absorbed in a negligible proportion (≈ 0.005%) in people with preserved kidney function.
• Distribution: Its action is strictly topical on the gastrointestinal epithelium.
• Metabolism: It does not undergo any metabolic biotransformation.
• Excretion: The unabsorbed fraction (95%) is eliminated completely and unaltered in the feces. The minimal sucrose sulfate absorbed is eliminated by renal filtration.

Indicators and dose

Approved and Off-label indications

• Short-term treatment (up to 8 weeks) of active duodenal ulcer.
• Prophylaxis of digestive bleeding due to stress in critically ill patients (with the theoretical advantage of not raising gastric pH and not facilitating retrograde pulmonary bacterial colonization, unlike PPIs).
• Mucositis induced by radiation or chemotherapy and severe peptic esophagitis (Off-label, through oral suspensions in gargles).

Dosage and Clinical Adjustment

Adults:

• Active duodenal ulcer: 1 g orally four times a day (1 hour before three main meals and at bedtime) on an empty stomach, for 4-8 weeks.
• Maintenance of healing: 1 g orally twice a day.

Adjustment in Renal Failure: No adjustment is required for the sucrose fraction. However, in severe renal failure (GFR < 30 mL/min) or dialysis, prolonged use should be avoided to prevent drug-induced aluminum toxicity.

Adjustment in Liver Failure: Does not require dose modifications.

Security

Risk of Bezoar and Intestinal Obstruction

Given its highly polymerizable and agglutinating nature, sucralfate has the ability to form insoluble complexes with food debris and gastric mucus. This significantly increases the risk of formation of gastric or esophageal bezoars, especially in patients admitted to intensive care units, subjects with diabetic or post-surgical gastroparesis, or those receiving continuous enteral nutrition through a nasogastric tube.

Contraindications

• Absolute: Known hypersensitivity to the components.
• Relative: End-stage chronic renal failure or renal osteodystrophy (risk of systemic aluminum accumulation and induction of encephalopathy, osteomalacia or dementia due to dialysis). Coadministration of continuous enteral nutrition formulas by tube.

Adverse effects (ADRs)

• Common (>1/100): Severe constipation (occurs in ≈ 2% to 3% of patients, due to the intrinsic astringent properties of the released aluminum hydroxide).
• Uncommon / Rare: Flatulence, dry mouth, nausea, indigestion, skin rashes.
• Serious (in special populations): Accumulation and systemic aluminum poisoning in patients with end-stage renal failure.

Drug interactions

• By interference with absorption (Physical Barrier): Sucralfate forms a film that drastically reduces the absorption and plasma levels of multiple drugs administered simultaneously: ciprofloxacin, levofloxacin, phenytoin, digoxin, warfarin, theophylline, levothyroxine, ketoconazole and tetracyclines. Management guideline: These drugs should be administered at least 2 hours before or 4 hours after the sucralfate dose.
• Interaction with Antacids: Sucralfate requires an acidic environment to polymerize and activate. Coadministration of potent antacids or PPIs may substantially reduce their gastric therapeutic efficacy.

Pregnancy and Breastfeeding

FDA Category B: Not associated with an increase in fetal malformations. Since maternal systemic absorption is extremely low, it is the drug of choice for the treatment of active peptic ulcers during pregnancy if systemic acid suppression is desired.

Breastfeeding: Compatible and safe. Since it is not absorbed, it is not excreted in breast milk and does not pose any risk to the infant.