PEPTIC ULCER PHARMA

1. KARAGANDA STATE MEDICAL UNIVERSITY
REPORT
PEPTIC ULCER
SUBJECT- PHARMACOLOGY
SUBMITTED TO-
SUBMITTED BY-
GROUP-
KGMU,2016

2. CONTENTS;-
 Physiology of Gastric acid secretion
 An introduction to Peptic Ulcer
Disease
 Drugs used in PUD

3. PHYSIOLOGY OF GASTRIC ACID SECRETION
• Food is broken into macroparticles
• Acid causes hydrolysis, sterilizes themeal content
& activates pepsinogen to pepsin
• Acid secretion:
• Basal
• Stimulated
DIAGRAM SHOWING OXYNTIC GASTRIC GLAND

4. GASTRIC PARIETAL CELL UNDERGOING TRANSFORMATION AFTER
SECRETAGOGUE MEDIATED STIMULATION

5. PHASES OF GASTRIC ACID SECRETION AND THEIR REGULATION

6. PATHOPHYSIOLOGY
PHYSIOLOGICAL REGULATION OF GASTRIC ACID SECRETION

8. PEPTIC ULCER DISEASE;-
• PEPTICULCER is defined as disruption of the mucosalintegrity of the
stomach and/or duodenumleading to a local defect or excavation due to
active inflammation.
Epidemiology
• Middle-age to older age .
• peptic ulcers - firstportion of the duodenum or in the stomach, in a ratio of
about 4:1.

9. • Male/female ratio is 3:1
CLINICAL PRESENTATION
• Epigastric pain
• Burning, aching, gnawing, hunger pain
 aggravated by food in Gastric ulcer ,
 relieved by food in Duodenal ulcer
• Bloating and nausea

10. • Loss of appetite and weight loss in Gastric ulcer
• In SevereCases
- Vomiting blood or coffee ground like material
- Black tarry stools
CLASSIFICATION OF ANTI-ULCER DRUGS;-
1.Drugs for reduction of acid secretion:
 Proton Pump Inhibitors:- Omeprazole, Lansoprozole, Dexlansoprazole
,Pantoprozole,Rabeprozole, Esomeprozole
 H2 receptor antagonists:- Ranitidine, Famotidine, Cimetidine ,Roxatidine
 Anticholinergics: - Pirenzepine, Propantheline ,Oxyphenonium
 Prostaglandin analogues: - Misoprostol
2.Drugs to neutralize gastric acid (antacids):
 Nonsystemic:- Aluminium hydroxide, Mag. hydroxide
Magaldrate , Mag. trisilicate ,Calcium carbonate .
 Systemic:- Sodiumbicarbonate , Sodiumcitrate

11. MISCELLANEOUS ADJUVANTS-
Simethicone
Sodiumalginate
3.Ulcer Protectives:
• Sucralfate,
• Colloidal Bismuth Subcitrateand Bismuth
Subsalicylate
• Ranitidine bismuth citrate
• Newer cytoprotectives- Rebamipide,Ecabet
4.Antimicrobial drugs for H. pylori eradication:
• Amoxycillin
• Clarithromycin
• Metronidazole
• Tinidazole
• Tetracycline
PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION OF GASTRIC ACID
SECRETION

12. PROTON PUMP INHIBITORS;-
• Diminish daily acid production (basaland stimulated) by 80-95%
• Absorbed fromsmall intestine at a pH of 6
• PPIs areprodrugs - acidic environment needed for activation.
MECHANISM OF ACTION
• After absorption prodrug gets activated to a tetracyclic sulfenamide cation
.
• Activated formthen binds covalently with sulfhydrylgroups of cysteines in
the H+
, K+
-ATPase, irreversibly inactivating the pump molecule.
• Maximum acid inhibitory effect between 2 and 6 hours after administration
and duration of inhibition lasting up to 72–96 hours.
• Because the pumps need to be activated for these agents to be effective,
their efficacy is maximized if they are administered beforemeal.

13. DOSAGE OF PPIs :-
• Omeprazole 20 mg OD
• Esomeprazole 20 - 40 mg OD
• Rabeprazole 20 mg OD
• Lansoprazole 30 mg OD
• Pantoprazole 40 mg OD
PPIs: ADRs
• Nausea, Diarrhea, Abdominal pain, Flatulence.
• Nosocomialpneumonia
• Clostridium difficle diarrhoea
• Hypergastrinemia, REBOUND hypersecretion of acid
• Arthralgia, headache, skin rashes.
Drug interactions :
 Decreased acidity may decreasethe absorption of Ketoconazole,
Ampicillin esters, Iron salts, Digoxin
 CYP2C19 and CYP3A4 enz inhibition 
 metabolism of benzodiazepines, warfarin, phenytoin, diazepam, theophylline
etc
 H2 RECEPTOR ANTAGONISTS;-
• Inhibit acid production by reversibly competing with histamine for binding to
H2 receptors on the basolateral membrane of parietal cells.
• Suppress acid productionby 70%
• Inhibit basal and stimulated acid secretion, which accounts for their efficacy in
suppressing nocturnal acid secretion.
• Ranitidine, Famotidine, Roxatidine, Nizatidine.

14. Adverse Drug Reactions of H2 antagonists;-
• Diarrhea, headache, drowsiness, fatigue, muscular pain, and constipation.
• Confusion, delirium, hallucinations, slurred speech
• REBOUND hyperacidity
• Pancytopenia, neutropenia, anemia, and thrombocytopenia
Dose of H2 antagonists;-
 Ranitidine 300 mg hs
 Famotidine 40 mg hs
 Nizatidine 300 mg hs
PROSTGLANDIN ANALOGUES;-
MISOPROSTOL- PGE1 ANALOGUE
• MOA- Binds to EP3 receptor on parietal cells and stimulate
Gi pathway- thereby decreasing intracellular cAMP &
gastric acid secretion.
• Cytoprotective effects
Daily dose –
• The usual recommended dose for ulcer prophylaxis is
200 micrograms four times a day.
Pharmacokinetics
• Inhibitacid sec.in 30 min.,peaks at 60-90 min.,lasts for 3 hrs.
Adverse effects
• Diarrhea
• Exacerbations of IBD
• C/I in pregnancy as increases uterine motility
ANTICHOLINERGICS (rarely usednow)

15.  SELECTIVE M1 BLOCKERS-PIRENZEPINE,TELENZEPINE
 The ACh receptor on the parietal cell is of the M3 subtype.
 Suppress neuralstimulation of acid production via actions on M1
receptors of intramural ganglia.
 Poor efficacy, significant and undesirableanticholinergic side effects, and
risk of blood disorders (pirenzepine)
ANTACIDS
• ALUMINIUM HYDROXIDE, MAGNESIUM HYDROXIDE,
MAGNESIUM TRISILICATE, CALIUM CARBONATE, MAGALDRATE
MOA-neutralises HCL and formAlCl3 and MgCl2 & Carbonates
• Fixed combinations of magnesium and aluminum
(Al3+
can relax gastric smooth muscle, producing delayed gastric emptying and
constipation; Mg2+
causes loosestools).
• The magnesium-containing preparations :
contraindicated in chronic renal failure patients because of possible
hypermagnesemia.
• Aluminum causes chronic neurotoxicity.
( Calcium Carbonate and SodiumBicarbonate rarely usednow a days.)
DRUG INTERACTIONS
• Aluminium and Magnesium ions form inert complexes-
Tetracyclines, Fluoroquinlones, Itraconazole, Digoxin or Iron salts
• Aluminium group of antacids decrease the bioavailability of
Phosphates, Iron salts and Digoxin
• By raising gastric pH and ionization, antacids decrease the
absorption of acidic drugs- Barbiturates, Phenytoin, NSAIDS .
SIMETHICONE

16. • Silicon polymer, reduces flatulence and hiccups
• Surfactant,antifoaming agent, cause proper dispersal of antacid
over gastric surface , coats ulcer base.
SODIUM ALGINATE-
• Hydrophilic colloidal carbohydrate derived from seaweeds
• Used with antacid & H2 antagonist-heart burn & GERD
ULCER PROTECTIVES
• SUCRALFATE-
• Complex sucrose salt - the hydroxyl groups substituted by
aluminum hydroxide and sulfate.
• MOA:
 Enhances prostaglandin synthesis,
 Stimulates mucus and bicarbonate secretion, and
 Enhances mucosal defense and repair.
Dose:
• 1 g four times daily (for active duodenal ulcer)
• 1 g twice daily (for maintenance therapy)
SIDE EFFECTS
• Constipation
• Avoided in pts. with chronic renal insufficiency to prevent
aluminum-induced neurotoxicity
• The "sticky" nature of the viscous gel - bezoars in some patients
with underlying gastroparesis.
COLLOIDAL BISMUTH SUBCITRATE & BISMUTH SUBSALICYLATE

17. • In acidic media CBS- forms acid resistant protective coating over
ulcer base
• Also stimulates mucosal PGE2 synthesis & HCO3- secretion
• Dislodges H.PYLORI from gastric mucosa –antimicrobial activity.
• Dose: 120 mg qid
• Heals ulcer in 4 – 8 wks
• ADRs- blackening of stool,darkening of tongue
• Prolonged use –Neuropathy,osteodystrophy, encephalopathy.
Anti H.pylori drugs;-
• Helicobacter pylori: gramnegative bacillus
• Attaches to gastric epithelium:gastritis, dyspepsia, peptic ulcer, gastric
lymphoma, gastric carcinoma.
• No single agent is effective in eradicating the organism.
• Combination therapy for 14 days provides the greatest efficacy
• The agents used with the greatest frequency include amoxicillin,
metronidazole, tetracycline, clarithromycin, and bismuth compounds.

18. • Choice of a particular regimen will be influenced by -
 Efficacy,
 Patient tolerance,
 Existing antibiotic resistance,
 Costof the drugs
• Two anti-H. pyloriregimens available in prepackaged formulation:
 Prevpac (lansoprazole, clarithromycin, and amoxicillin)
 The contents taken twice per day for 14 days
 Helidac (BSS, tetracycline, and metronidazole).
 Helidac constituents taken four times per day with an antisecretory
agent (PPI or H2 blocker), also for at least 14 days.

19. TRIPLE THERAPY;-
 The BEST among all the Triple therapy regimens is
Omeprazole /Lansoprazole - 20 / 30 mg BD
Clarithromycin - 500 mg BD
Amoxycillin - 1gmBD
Given for 14 days followed by P.P.I for 4 – 6 weeks
QUADRUPLE THERAPY;-
GIVENWHENTRIPLETHERAPY FAILS
Omeprazole/lansoprazole - 20 / 30 mg OD
Bismuthsubsalycilate - 525 mg
Metronidazole - 250 mg QID
Tetracycline - 500 mg QID
SEQUENTIAL THERAPY (10 DAYS);-
For 1-5 days
• Omeprazole /lansoprazole -20 mg/30mg BD
• Amoxicillin -1 g BD
Followed by 6-10 days
• Omeprazole/lansoprazole -20mg/30mg BD
• Clarithromycin -500 mg BD
• Tinidazole -500 mg BD
Major SIDE EFFECTS of drugs;-
• Bismuth : black stools, constipation, or darkening of the tongue.
• Amoxicillin : nausea, vomiting, skin rash,
allergic reaction , pseudomembranous colitis ,
antibiotic-associated diarrhea.
• Tetracycline : rashes and, very rarely, hepatotoxicity and anaphylaxis.

20. Treatment of patients infected with resistant strains of
H.pylori
• Regimens considered for second-line therapy include:
• Combi. of Pantoprazole, Amoxicillin, and Rifabutin for 10 days (86% cure
rate)
• Levofloxacin-based triple therapy
(Levofloxacin, Amoxicillin, PPI) for 10 days .
• furazolidone-based triple therapy
(Furazolidone, Amoxicillin, PPI) for 14 days.
THANK YOU