ANTI ULCER AGENTS
The Digestive System
PEPTIC ULCERS Is erosion in the lining of the stomach or duodenum. The word peptic refers to pepsin, stomach enzyme that breaks down proteins. Occur when there is a hyper secretion of hydrochloric acid and pepsin which erode the GI mucosal lining
Predisposing Factors: Mechanical disturbances Genetic influences Bacterial organisms Environmental factors Certain drugs
Duodenal & Gastric Ulcer
CLASSIC SYMPTOM OF PEPTIC ULCER Gastric ulcer: Pain occurs 30 mins to 1.5 hrs after eating Duodenal ulcer: Pain occurs 2-3 hours after eating.
Stress Ulcer: Usually follows a critical situation such as extensive trauma or major surgery
HELICOBACTER PYROLI (H. Pylori) Gram negative bacillus Known to cause: Gastritis Gastric ulcer Duodenal ulcer
TREATMENT The use of only one antibacterial agent is not effective for eradicating [Link]
A. Bismuth 2 tabs QID + Amoxicillin 500mg cap TID Tetracycline 500mg 1 cap QID + Metronidazole 500mg tab PO X 2 weeks
B. Amoxicillin 500mg cap TID + Omeprazole 20mg cap BID PO X 2 weeks C. Omeprazole 20mg cap BID + Clarithromycin 500mg tab BID X 1 week s + Metronidazole 500mg tab PO X 2 weeks
D. Ranitidine/Bismuth(pylorid)400m g 1 tab BID + Clarithromycin 500mg tab BID X 1-2 weeks
7 GROUPS OF ANTI ULCER DRUGS: 1. Tranquilizers 2. Anticholinergic 3. Antacids 4. H2 blockers 5. PPIs 6. Pepsin Inhibitor Sucralfate 7. Prostaglandin E analogue Misoprostol
TRANQUILIZER Have minimal effect in preventing & treating ulcers Decrease vagal stimulation & anxiety Example: LIBRAX Combination of anxiolytic chlordiazepoxide and the Anticholinergic clidirium bromide
ANTICHOLINERGICS Decrease acetylcholine by blocking the cholinergic receptors Relieve pain by decreasing GI motility & secretion. Delays gastric emptying time so they are used frequently for duodenal ulcer than gastric ulcer.
Should be taken before meals to decrease the acid secretion that occurs with eating.
Antacids can slow the absorption therefore should be taken 2 hours after Anticholinergic is administered.
Side effects & Adverse Reactions
Dry mouth Tachycardia Urinary retention Constipation milk-alkali syndrome
Milk-alkali syndrome Is intensified if milk products are ingested with calcium carbonate.
Confirmed by: Presence of alkalosis, hypercalcemia, crystalluria & renal failure
Non Systemic Effect: Composed of alkaline salts: A. Aluminum (Aluminum hydroxide, aluminum carbonate) B. Magnesium (Magnesium hydroxide, magnesium carbonate)
Magnesium compounds: Can cause diarrhea Aluminum compounds: Can cause constipation
A combination of magnesium & aluminum salts neutralizes gastric acid without causing severe diarrhea & constipation.
Pharmacokinetics
Aluminum Hydroxide: Small amount is absorbed in the GIT Primarily bound to PO4 & excreted in the feces Small portion excreted in the urine
Pharmacodynamics
Neutralizes gastric acid including HCL inc. the pH of gastric secretion Ideal Dosing Intervals: 1 and 3 hours after meals and at bedtime
Ideal Dosing Intervals:
Antacids taken on empty stomach are effective for 30-60 mins before passing into the duodenum. chewable tablet should be followed by H2O (24oz)
Contraindications: Impaired renal function because of risk of hypermagnesemia. Prolonged use of ALOH can cause hyponatremia.
HISTAMINE 2 BLOCKERS (H2 Blockers)
Most popular drugs used in the treatment of gastric & duodenal ulcers. Prevent acid reflux in the esophagus (reflux esophagitis) Blocks the H2 receptors of the parietal cells in the stomach
3 H2 Blockers RANITIDINE (Zantac 1983) FAMOTIDINE (Pepcid 1986) NIZATIDINE (Axid 1988) More potent than cimetidine Duration of Action: long Fewer side effects & drug interactions
TAGAMET 1ST H2 blocker in 1975 Short half life Short Duration of Action Blocks about 70% of acid secretion for 4 hours Good kidney function
Pharmacokinetics Ranitidine: Is 5-12X more potent than cimetidine but less potent than famotidine. Rapidly absorbed & reach the peak concentration after a single dose. Has a low protein-binding
Pharmacokinetics
50% excreted unchanged in the urine Ulcer healing for 8 weeks is 90% Large doses are effective for controlling Zollinger-Ellison Syndrome
Zollinger-Ellison Syndrome
Pharmacodynamics Ranitidine Inhibits histamine at H2 receptor site Effective in the treatmentx of gastric & duodenal ulcer. Relieves symptom of reflux esophagitis
Prevents aspiration pneumonitis that can result from aspiration of gastric acid secretion.
Neither cimetidine nor Ranitidine should be taken with antacids because their H2 blocking action could be decreased.
Famotidine is 50-80% more potent than cimetidine is 5-8x more potent than ranitidine indicated for short term use (4-8 wks)(duodenal ulcer)
Nizatidine Latest H2 blocker Relieve nocturnal gastric acid secretion for 12hours. Similar to famotidine in protein binding & half-life
PROTON PUMP INHIBITORS (PPIs) Suppresses gastric acid secretion by inhibiting the H/K ATPase enzyme Inhibit acid secretion by 90% greater than H2 blockers
PROTON PUMP INHIBITORS (PPIs)
EXAMPLES: prazole lanzoprazole rabeprazole pantoprazole esomeprazole Duration of treatment: 4-8 weeks
PEPSIN INHIBITOR (Mucosal Protective Drug Ex:Sucralfate (Carafate) A complex of sulfated sucrose & Aluminum hydroxide Non absorbable & combines with protein to form a viscous substance that covers the ulcer & protect it from acid & pepsin.
Does not neutralize acid nor decrease acid secretions
Side effects: Constipation Dosage: 1 gram QID AC & HS
PROSTAGLANDIN ANALOGUE
Ex: Misoprostol (Cytotec) Appears to suppress gastric acid secretions & increase cytoprotective mucus in the GI tract. Causes moderate decrease in PEPSIN secretions As effective as Cimetidine
PROSTAGLANDIN ANALOGUE
WHEN CLIENT IS TAKING HIGH DOSES OF NSAIDS, they frequently recommended for the duration of the NSAID therapy Contraindication: Pregnancy
