Carmel Christy MM20505 MD STUDENT

L10: Drugs in peptic ulcer and biliary diseases

Drugs in peptic ulcer

• Classification
o Neutralization of secreted acid
▪ Non-systemic: Antacid
▪ Systemic: Sodium bicarbonate & Calcium bicarbonate
o Reduction of gastric acid secretion
▪ H2 receptor antagonists
▪ Proton pump inhibitor (PPI)
▪ Anti-cholinergic drugs
o Mucosal protective agents
▪ Sucralfate, Prostaglandin analogues (Misoprostol) & Colloidal bismuth compounds

Antacid
(Neutralization of secreted acid)
Properties • Weak bases
• Neutralizes intragastric HCl to form salt and H2O
• Only formed acid are neutralized
• Given after meal
• A single dose (156mEq) given 1hrs after meal → neutralized up to 2hrs

Mode of 1. Antacid reacts with gastric HCl → Salt and H2O (Neutralize)
action 2. Promote mucosal defence mechanism by stimulating mucosal prostaglandin production
3. ↓ Pepsin activity (Pepsin is inactive in solution above pH 4)

Clinical • Relief pain from oesophagitis, gastric and duodenal ulcer

uses • Promote healing of duodenal ulcer (Gastric ulcer  Less effective)
• Used in dyspepsia & acid peptic disorder

Adverse • Systemic antacid (Sodium bicarbonate & Calcium bicarbonate) → Belching, Distension,
effect Metabolic alkalosis, Hypercalcaemia, Renal insufficiency, Nephrolithiasis, Rebound acidity
• Mg(OH)2 (Magnesium hydroxide) → Diarrhoea
• Al(OH)3 (Aluminium hydroxide) → Constipation
• Drug interaction → ↓ absorption of many drugs (Tetracyclines, Iron, Ketoconazole,
Fluroquinolones)

Ideal ➔ Mg(OH)2 + AL(OH)3 [Administered after meal]

combo Advantages:
➔ It reacts slowly with HCl → Magnesium chloride, Aluminium chloride, & H2O
➔ No gas generated → No Belching
➔ Metabolic alkalosis would be uncommon
Carmel Christy MM20505 MD STUDENT

➔ Since Mg(OH)2 cause diarrhoea and AL(OH)3 cause constipation → Both minimize the
impact upon bound function

H2 receptor blocker
(Reduction of gastric acid secretion)
Properties • Highly selective
• Generally, well tolerated
• Over the counter drug
Examples Cimetidine, Ranitidine (Now banned), Famotidine, Nizatidine
Pharmacokinetics • It is rapidly absorbed from gastrointestinal tract (GIT)
• 1st pass metabolism → Cimetidine, Famotidine, & Ranitidine(banned)
• Serum half life → 1.1 – 4 hours
• Excretion → Glomerular filtration & renal tubular secretion
Mode of action • The H2 antagonists competitively & reversibly bind with H2 receptor present on
cell membrane of gastric parietal cell → Inhibit the action of H2 receptor → ↓ HCl
secretion
• Also ↓ acid secretion that are stimulated by gastrin & cholinergic drugs
Clinical uses • Gastro-oesophageal reflux disease (GERD)
• Peptic ulcer disease – uncomplicated gastric & duodenal ulcer → 6-8 wees, heals
ulcer > 80-90%
• NSAIDs induced ulcer
• Prevent bleeding from stress related gastritis
Adverse effects • Diarrhoea, Headache, Fatigue, Myalgia, Constipation
• CNS → Confusion, hallucination, agitation
• Endocrine → Cimetidine inhibits binding of dihydrotestosterone → May cause
galactorrhoea in women & Gynaecomastia or impotence in men
Carmel Christy MM20505 MD STUDENT

Proton Pump Inhibitor _aka_ PPI

(Reduction of gastric acid secretion)
Properties • Benzimidazole group
• Ideal drug & now most widely used drug. Superior to H2 receptor blocker.
• Pro-drugs, highly efficacious, safe
• Single dose can inhibit 90-98% of HCl secretion
• Available in oral form, lipophilic & weak base
• Short half life
• Concentrated and activated near site of action
• Long duration of action
Examples Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole
P/kinetics • Can be give orally, but I/V also available
• Bioavailability ↓ 50% with food → Given in empty stomach, 1hr b4 meal
• Acid labile pro-drug, lipophilic, weak bases
• Given in enteric coated formulation (bc it is acid labile pro-drug)
• Half life → Abt 1.5hrs
• Duration of inhibition last up to 24hrs bc irreversible inactivation of H+/K+-ATPase pump
• Rapid 1st pass & systemic hepatic metabolism
• Excreted by kidney (very less)
Mode of • PPI which is absorbed in intestine and rapidly enter into Parietal cell canaliculi &
action concentrated within parietal cell > 1000 folds → Irreversible inactive H+/K+-ATPase and
block final common pathway of acid secretion
Clinical • Gastro-oesophageal reflux disease (GERD)
uses • Peptic ulcer disease:
Duodenal ulcer → Heal 90% ulcer within 4 weeks
Gastric → Heal 90% ulcer within 6-8 weeks
• NSAIDs induced ulcer
• Prevention of re-bleeding from peptic ulcer
• Non-ulcer dyspepsia
• Prevention of stress related mucosal bleeding
Eradication • PPI → ↑ intra-gastric pH → ↓ minimum inhibitory concentration (MIC) of antibiotic
of against H. pylori
H.pylori • Minor direct anti-microbial property
infection
Adverse 1. Diarrhoea, Headache, Abdominal pain
effect 2. Nutrition → ↓ Vit.B12 absorption
3. Hypergastrinoma → ↑ gastrin level which causes long term use
↑ in proliferation of colonic mucosa which will cause carcinogenesis
Carmel Christy MM20505 MD STUDENT

Hyperplasia of ECL (Enterochromaffin-Like) cells causing Gastric carcinoid tumour

Sucralfate
(Mucosal protective agents)
Chemistry Salt of sucrose complexed to sulphated Al(OH)3
Pharmacokinetics Poorly absorbed from GIT → Less than 3% of intact drug & aluminium is absorbed
from GIT, remainder is excreted in faces
Mode of action • Breaks down into sucrose sulphate and aluminium salt in acidic environment
• Sucrose sulphate is strongly negative charged
• Sucrose sulphate binds to positive charged proteins in the base of the ulcer or
erosion → forms a viscous tenacious paste & acts as a physio-barrier that prevent
further damage
• Sucralfate also stimulates prostaglandin & bicarbonate secretion
Clinical uses • Limited CU
(CU) • Healing of duodenal ulcer
• Decrease upper GIT bleeding in ill patient
• Prevention of stress related bleeding
Adverse effect • Virtually devoid of systemic adverse effect (Almost no adverse effect)
• Constipation (2%) due to aluminium

Prostaglandin Analogous → Misoprostol (PGE1 Analogue)

(Mucosal protective agents)
Description • Misoprostol a Prostaglandin E1 analogue (PGE1 Analog)
Pharmacokinetics • Rapidly absorbed
• Serum half-life → Less than 30 minutes
• Excreted in urine
Mode of action 1. Misoprostol binds to the prostaglandin receptor on parietal cells which decrease
histamine induced cAMP production → Causing modest acid inhibition
2. Mucosal protective action → stimulate mucous & bicarbonate secretion & enhance
mucosal blood flow
3. Other action:
- Stimulate intestinal electrolyte & fluid secretion
- Stimulate intestinal motility
- Stimulate uterine contraction
Clinical uses NSAIDs induced ulcer
Adverse effect • Nausea
• Cramping abdominal pain
• Stimulate uterine contraction
Contradiction Pregnancy
Carmel Christy MM20505 MD STUDENT
Carmel Christy MM20505 MD STUDENT

Colloidal Bismuth Compound

(Mucosal protective agents)
Examples • Bismuth subsalicylate → Bismuth + Salicylate (USA available)
• Bismuth subcitrate
• Bismuth dinitrate
Ps, can get otc
Pharmacokinetics • Rapid dissociation within stomach
• Allowing absorption of salicylate
• More than 99% appears in stool
• Stored in many tissues
• Slow renal excretion
Mode of action 1. Selectively chelates (type of bonding of ions and molecules to metal ions) with
protein material in the ulcer base & form coating and creates a protective layer
against acid & pepsin
2. May stimulate prostaglandins, mucous & bicarbonate secretion
3. Direct anti-microbial activity against H. pylori
Clinical uses • Non-specific dyspepsia
• Acute diarrhoea → Colloidal Bismuth C Decrease frequency & liquidity of stool
• Prevention of traveller’s diarrhoea
• Triple therapy (as a 2nd line therapy): For eradication of H. pylori
(Bismuth subsalicylate, tetracycline & metronidazole)
Adverse effect Excellent safety profile
• Blackening of stool
• Harmless darkening of tongue
• Encephalopathy → Ataxia, headache, confusion & seizure (Rare prolonged use)
• Salicylate toxicity (high dose)
Carmel Christy MM20505 MD STUDENT

Drugs in biliary diseases

Drugs that dissolve non-calcified cholesterol

Examples • Chenodeoxycholic acid (CDCA)
• Ursodeoxycholic acid (UDCA)
Adverse effect • Diarrhoea
Mode of • Selected patients with gallstones as surgery is the preferred treatment in most cases
action when active intervention is needed

Drugs affecting biliary spasm

What? • Drugs which relieve the pain produced by the passage of gallstones down the bile
duct (bile cholic)
Examples • Morphine
• Buprenorphine
• Pethidine
• Atropine → Commonly use bc has antispasmodic action
Mode of • Selected patients with gallstones as surgery is the preferred treatment in most cases
action when active intervention is needed