Peptic ulcer treatment
Post on 23-Aug-2014
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Pharmacotherapy of Peptic ulcer
Objectives Regulation of Gastric acid secretion Classification of drugs used in peptic
ulcer Mechanism of action, Uses & Adverse
effects, drug interactions of H2 Blockers Proton pump inhibitors Antacids Ulcer protectives
Drugs for eradication of H.pylori
Why Peptic ulcer occurs Imbalance primarily between Aggressive
factors and Defensive factors
Aggressive
factors, e,g,
acid, pepsin,
bile , H.pylori.
Defensive
factors, e.g.
mucus,
HCO3, PG,
NO
Formation of HCL
Regulation of gastric acid secretion
Classification of drugs used in peptic ulcer 1. Drugs that inhibit gastric
acid secretion 2. Drugs that neutralize
gastric acid (Antacids)3. Ulcer protectives 4. Anti H. pylori drugs
Classification (Contd.)
Drugs that inhibit gastric acid secretion H2 receptor blockers: Cimetidine,
Ranitidine, Famotidine Proton pump inhibitors: Omeprazole,
Pantoprazole, esomeprazole Anticholinergics : Pirenzepine Prostaglandin analogues: Misoprostol
Classification (Contd..) Drugs that neutralize gastric acid
(Antacids) Systemic:
• Sodium bicarbonate, sodium citrate Non systemic:
• Magnesium hydroxide, Mag. Trisilicate, Aluminium hydroxide gel, Magaldrate
Classification (Contd..) Ulcer protectives
Sucralfate Colloidal Bismuth Sulfate (CBS)
Anti H. pylori drugs Amoxicillin, Clarithromycin,
Metronidazole, Tinidazole, Tetracycline
H2 ANTAGONISTS
Mechanism of action Competitively block H2 receptors on
parietal cell & inhibit gastric acid production
Supress secretion of acid in all phases but mainly nocturnal acid secretion
Also reduce acid secretion stimulated by Ach, gastrin, food, etc.
Pharmacokinetics Absorption is not interfered by food Can cross placental barrier and reaches milk,
Poor CNS penetration The serum half-lives range from 1.1 to 4
hours; Cleared by a combination of hepatic
metabolism, glomerular filtration, and renal tubular secretion.
Dose reduction needed in moderate to severe renal insufficiency
Bioavailability 80 50 40 >90
Relative Potency 1 5 -10 32 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
DOA (hrs) 6 8 12 8
Inhibition of 1 0.1 0 0
CYP 450
Dose mg (bd) 400 150 20 150
Cimetidine Ranitidine Famotidine Nizatidine
Comparison of H2 antagonists
H2 antagonists - UsesPromote the healing of gastric and duodenal ulcers Duodenal ulcer – 70 to 90% at 8 weeks Gastric Ulcer – 50 to 75% NSAID ulcers induced ulcers Stress ulcer and gastritis GERD Zollinger-Ellison syndrome Prophylaxis of aspiration pneumonia
Adverse effects Headache, dizziness, bowel upset, dry
mouth CNS: Confusion, restlessness Bolus IV – release histamine –
bradycardia, arrhythmia, cardiac arrest Cimetidine has antiandrogenic actions
Drug interactions Cimetidine inhibits several CYP-450
isoenzymes and reduces hepatic blood flow, so inhibits metabolism of many drugs like theophylline, metronidazole, phenytoin, imipramine etc.
Antacids reduce the absorption of all H2 blockers
Proton Pump Inhibitors Most effective drugs in antiulcer therapy Prodrugs requiring activation in acid
environment Activated forms binds irreversibly to
H+K+ATPase and inhibit it
Omeprazole Pantoprazole Lansoprazole Esomeprazole
Mechanism of Action Prodrugs inactive at neutral pH
At pH < 5 rearranges to two charged cationic
forms (sulfenamide + sulphenic acid) that bind
covalently with SH groups of H K ATPase and ⁺ ⁺inactivate it irreversibly
Also inhibits gastric mucosal carbonic anhydrase
Pharmacokinetics - PPI Available as enteric coated tablets They should be given 30 minutes to 1 hour
before food intake half life is very short and only 1-2 Hrs Still the action persists for 24 Hrs to 48 hrs after a
single dose Action lasts for 3-4days even after stoppage of
the drug
PPI – contd. Therapeutic uses:
1. Gastroesophageal reflux disease (GERD)2. Peptic Ulcer - Gastric and duodenal ulcers3. Bleeding peptic Ulcer 4. Zollinger Ellison Syndrome5. Prevention of recurrence of nonsteroidal
antiinflammatory drug (NSAID) - associated gastric ulcers in patients who continue NSAID use.
6. Reducing the risk of duodenal ulcer recurrence associated with H. pylori infections
7. Aspiration Pneumonia
Comparative success of therapy with PPI and H2 antagonist
Adverse Effects Nausea, loose stools, headache
abdominal pain, constipation, Muscle & joint pain, dizziness, rashes Rare
Gynaecomastia, erectile dysfunction Leucopenia and hepatic dysfunction Osteoporosis in elderly on prolonged use Hypergastrinemia
Drug interactions Omeprazole inhibits the metabolism
of warfarin, phenytoin, diazepam, and cyclosporine.
However, drug interactions are not a problem with the other PPIs.
PPI – Dosage schedule Omeprazole 20 mg o.d. Lansoprazole 30 mg o.d. Pantoprazole 40 mg o.d. Rabeprazole 20 mg o.d. Esomeprazole 20-40 mg o.d
Proton Pump Inhibitors Lansoprazole :
Partly reversible, more potent, slightly more against H pylori, Higher BA, rapid onset.
Pantoprazole: More acid stable, I.V, CYP450 less affinity
Rabeprazole: claimed to most rapid Es-omeprazole
Better intragastric pH , higher healing rates.
Muscarinic antagonists
Block the M1 class receptors Reduce acid production, Abolish gastrointestinal
spasmPirenzepine and Telenzepine Reduce meal stimulated HCl secretion by reversible
blockade of muscarinic (M1) receptors on the cell bodies of the intramural cholinergic ganglia
Unpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurred vision)
Prostaglandin analogues- Misoprostol Inhibit gastric acid secretion Enhance local production of mucus or
bicarbonate Help to maintain mucosal bloodTherapeutic use:
Prevention of NSAID-induced mucosal injury (rarely used because it needs frequent administration – 4 times daily)
Misoprostol Doses: 200 mcg 4 times a day ADRs:
Diarrhoea and abdominal cramps Uterine bleeding Abortion Exacerbation of inflammatory bowel disease and
should be avoided in patients with this disorderContraindications:1. Inflammatory bowel disease2. Pregnancy (may cause abortion)
Antacids Weak bases that neutralize acid Also inhibit formation of pepsin (As pepsinogen converted to pepsin at
acidic pH) Acid Neutralizing Capacity:
Potency of Antacids Expressed in terms of Number of mEq of 1N
HCl that are brought down to pH 3.5 in 15 minutes by unit dose of a preparation (1 gm)
Systemic antacids Sodium Bicarbonate:
Potent neutralizing capacity and acts instantly ANC: 1 gm = 12 mEq
DEMERITS: Systemic alkalosis Distension, discomfort and belching – CO2
Rebound acidity Sodium overload
Non systemic antacids Insoluble and poorly absorbed basic
compounds React in stomach to form
corresponding chloride salt The chloride salt again reacts with
the intestinal HCO3- so that HCO3- is not spared for absorption
Non systemic Antacids Magnesium hydroxide (ANC 30 mEq)
Aqueos suspension is called Milk of magnesia
Magnesium trisilicate (ANC 10 mEq) Aluminium Hydroxide (ANC 1-2.5mEq/g)(Magaldrate – hydrated hydroxy magnesium
aluminate)
Non systemic antacids Duration of action : 30 min when taken in empty
stomach and 2 hrs when taken after a meal Adverse effects:
Aluminium antacids – constipation (As they relax gastric smooth muscle & delay gastric emptying) – also hypophosphatemia and osteomalcia
Mg2+ antacids – Osmotic diarrhoea In renal failure Al3+ antacid – Aluminium toxicity
& Encephalopathy
Miscellaneous drugs Simethicone: Decrease surface
tension thereby reduce bubble formation - added to prevent reflux
Alginates: Form a layer of foam on top of gastric contents & reduce reflux
Oxethazaine: Surface anaesthetic
Chemical reactions of antacids with HCl in the stomach
Drug interactions By raising gastric pH & forming insoluble
complexes ↓ absorption of many drugs Tetracyclines, iron salts, H2 Blockers,
diazepam, phenytoin, isoniazid, ethambutol
Sucralfate – ulcer protective Aluminium salt of sulfated sucrose MOA:
In acidic environment ( pH <4) it polymerises by cross linking molecules to form sticky viscous gel that adheres to ulcer crater - more on duodenal ulcer
Astringent action and acts as physical barrier Dietary proteins get deposited on this layer
forming another coat
Sucralfate – contd. Concurrent antacids avoided, (as it needs acid for
activation) Uses:
Prophylaxis of Stress ulcers Bile reflux gastritis Topically – burn, bedsore ulcers, excoriated skins
Dose: 1 gm 1 Hr before 3 major meals and at bed time for 4-8 weeks
ADRs: Constipation, hypophosphatemia Drug interactions : adsorbs many drugs and
interferes with their absorption
Colloidal Bismuth Subcitrate (CBS) Mechanism of action
CBS and mucous form glycoprotein bi complex which coats ulcer crater
↑ secretion of mucous and bicarbonate, through stimulation of mucosal PGE production
Detaches H.pylori from surface of mucosa and directly kills them
Colloidal Bismuth subcitrate Dose: 120 mg 4 times a day Adverse effects
blackening of tongue, stools, dentures Prolonged use may cause
osteodystrophy and encephalopathy Diarrhoea, headache, dizziness
Eradication of H.pylori
No acidNo ulcerOLD TESTAMENT
No HP No ulcer
NEW TESTAMENT
H. pylori Gram (-) rod Associated with gastritis,
gastric & duodenal ulcers, gastric adenocarcinoma
Transmission route fecal-oral Secretes urease → convert
urea to ammonia Produces alkaline
environment enabling survival in stomach
Higher prevalence in Low SES
Who are they ?
Barry J Marshall J. Robin Warren
Nobel Laureates of Medicine – 2005
Discovery of H. pylori & its role in peptic
ulcer
Triple TherapyThe BEST among all the Triple therapy regimen is:
Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks
Short regimens for 7 – 10 days not very effective
Other 2 weeks regimen(mg) Amoxicillin 750/ + Tinidazole 500
+omeprazole 20 mg/ lansoprazole 30 mg BD
clarithromycin 250 + Tinidazole 500/amoxicillin 1000 + lansoprazole 30 mg BD
Thank You
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