peptic ulcer disease
DESCRIPTION
Basics of Therapeutics for Pharm D studentsTRANSCRIPT
By: Dr. Abhimanyu Prashar
PUD: “A condition in which there is a discontinuity in the entire thickness of the gastric or duodenal mucosa”
Ulcers:
“The areas of degeneration and necrosis of gastrointestinal mucosa exposed to acid and pepsin
secretion”
Regulation of gastric acid secretion
Mediated by 3 pathways: Neurocrine (Ach)Paracrine (Histamine)Endocrine (Gastrin)
• Activation of proton pump exchange of H+
• In addition, histamine, gastrin & ach receptors stimulate H+ production
• Ach from post ganglionic vagal neurons• Gastrin fron antral G cells stimulates pepsinogen secrection,
hepatic bile flow & pancreas (insulin)
It also stimulates gastric & intestinal motility
Directly stimulates Hcl secretion by acting on gastrin receptors on parietal cells
Gastrin activates ECL cells which releases histamine
Histamine activates H2 rec, results in activation adenylate cyclase which convers ATP to cAMP and subsequent generation of H+ & proton pump mobilses & activated
Autoregulatory mechanism: Ingestion of meal gastrin release gastric acid
secretion decreased PH release of somatostatin from D cells decreased release of gastrin, inhibits acid secretion, suppress histamine release
Other NTs, vasoactive intestinal peptide, galanine, serotonin, are also involved in direct or indirect regulation of gastric acid secretion
Epidemiology PUD is more common in unskilled labourers and low socioeconomic
groups
Smokers and individuals who are on NSAIDs are more prone to develop PUD
About 10% of the population in developed countries likely to be affected by PUD
Duodenal ulcer is 4 times more common than gastric ulcer
Etiopathogenesis
Infection with Helicobacter pylori
Use of NSAIDs
Local irritants
Dietary factors
Hormonal factors
Decreased mucous secretion
H.pyloriA spiral gram negative bacterium
95% of duodenal ulcers & 85% of gastric ulcers are associated with H.pylori infection
H.Pylori produces Cag A proteins and vacuolating cytotoxins (Vac A) which activates inflammatory cascade
It expresses sialic acid specific haemagglutinins and a lipid binding adhesion that mediate binding to the mucosal surface
Enzymes like urease, haemolysins, neuraminidase and fucosidase involve in tissue damage
Altered gastrin homeostasis in H.pylori infection
Hypergastinaemia leads to inflammation and ulcer formation
Use of NSAIDs
NSAIDs cause 3 patterns of mucosal damage Superficial erosions & haemorrhagesSilent ulcers detected at endoscopyUlcers causing clinical symptoms
Mechanism: reduction of mucosal PGs production
Approx. 20% of patients taking NSAIDs experience Dyspepsia
Approx. 4% of NSAID users suffer from ulcer and ulcer complications
Local irritants
Pyloric antrum & lesser curvature of stomach most exposed
for longer periods of irritants (like spicy food, alcohol,
tobacco smoking) hence these are common sites for
occurrence of gastric ulcer
Dietary factors
Poor socio-economic status (malnutrition)
Irregular food habits
Social habits
Consumption of spicy food
Hormonal factors
Zollinger-Ellison syndrome (acid secreting tumours) leads to massive hypersecretion of gastric acid
Decreased mucous secretion
Conditions like stress, anxiety that decreases quantity
or quality of normal protective mucous barrier predisposes
to the development of PUD
Clinical features
Duodenal ulcer
• Pain-food relief pattern• Night pain common• No vomiting• Melena (blood in stool)
more common• No loss of weight
Gastric ulcer
• Food-pain pattern• No night pain• Vomiting present• Hematemesis (blood in
vomit) more common• Significant loss of weight
Investigations
Endoscopy
Radiology
H. pylori detection:
Serology to detect Abs
Urea breath test
Histology & culture
Management
Triple therapy
Omeprazole 20 mg PO bid+
Clarithromycin 500 mg PO bid for 7 days+
Amoxicillin 1 gram PO bid
Omeprazole 20 mg PO bid+
Clarithromycin 500 mg PO bid for 7 days
+Metronidazole 400 mg PO tid
Quadruple therapy
Bismuth 107.7 mg PO qid+
Metronidazole 200 mg PO tid & 400 mg at night
+Tetracycline 500 mg PO qid
for 14 days+
Omeprazole 20 mg or Lansoprazole 30 mg or Pantoprazole 40 mg PO bid
Follow on antisecretory therapy for complicated ulcers and larger ulcers of ≥ 1 cm
diameter H2 Rec antagonists
Ranitidine 300 mg POor
Nizatidine 300 mg POor
Famotidine 40 mg POor
Cimetidine 800 mg PO
With evening meal For additional 4-6 weeks
PPIs
Pantoprazole 40 mg PO or
Lansoprazole 30 mg PO or
Omeprazole 20 mg PO or
Rabeprazole 20 mg PO
For additional 2-4 weeks
Bleeding peptic ulcers
Endoscopic haemostasis using a heater probeor
Inj. Adrenaline 1: 10000 or 1: 100000
Omeprazole 80 mg as a bolus dose then 8 mg/hr infusion for 3 days
Stress ulceration prophylaxis
Ranitidine 300 mg PO 1-0-1or
Famotidine 40 mg PO 1-0-1or
Sucralfate 1 gram every 6 hourlyor
Omeprazole 20/40 mg PO 1-0-1or
Pantoprazole 20/40 mg PO 1-0-1
Antacids
Magnesium hydroxide (1g≈ 30 m eq HCl)
Magnesium trisilicate (1g ≈ 10 m eq HCl)
Aluminium hydroxide gel (5 ml ≈ 1 m eq HCl)
Calcium carbonate (1g ≈ 20 m eq HCl)
Sodium bicarbonate (1 g ≈ 12 m eq HCl)
Sodium citrate (1g ≈ 12 m eq HCl)
Ulcer protective drugs
Sucralfate (aluminium salt of sulphated sucrose)
Colloidal bismuth sub citrate
Prostaglandin analogues:
Misoprostol (methyl PGE1 ester) 200 mcg
Anticholinergics:
Pirenzepine 100-150 mg/day
Drugs causing dyspepsiaCorticosteroidsBisphosphonates Potassium chlorideIronAntibioticsCCBsNitratesTheophyllineDrugs with anti muscarinic effects e.g. TCAsNSAIDs:
High risk: Long acting - piroxicam, ketoprofenlow risk: short acting- ibuprofen, diclofenacreduced risk: highly selective COX-2 inhibitors
ZES
Characterized by severe peptic ulceration,
gastric acid hyper secretion and a non β-cell
islet tumor of the pancreas (gastrinoma)
ZES is the cause of about 0.1 % of cases of duodenal ulceration
Gastrinoma
Large amount of gastrin
Parietal cells
Maximal acid secretion & increased parietal cell mass
Increased acid output
Reduced luminal PH to 2 or less
Inactivate pancreatic lipase & precipitates bile acids
Diarrhea & steatorrhoea
Secretes
Stimulates
Path
ogen
esis
Clinical features:Diarhoea & Steatorrhoea
Investigations:serum gastrin levelsEndoscopic ultrasound
Management
Non-pharmacological:Tumor resection
Pharmacological:Omeprazole 60-80 mg/D
Synthetic somatostatin analogue:Octreotide SC 200-300 mcg/D
BD