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Drugs For Peptic Ulcer
Drugs For Peptic Ulcer
Ulcers occur five times more commonly in the duodenum, where over 95%
are in the bulb or pyloric channel.
In the stomach, benign ulcers are located most commonly in the antrum (60%)
and at the junction of the antrum and body on the lesser curvature (25%).
e capacity Elaboration
regenerativ of
Epithelial prostaglandi
n
• Elaboration of
prostaglandin
Mucosal defence
mechanism
Aggressive forces
H.Pylori
NSAIDS
infection
Corticosteriods cigarette
alcohol
Associated disease
Chronic renal
Cirrhosis
failure
Zollinger
ellison
syndrome
MANAGEMENT
Endoscopic
procedures are
investigation
of choice.
Goals of antiulcer therapy
Relief of pain
Ulcer healing
Prevention of complications (bleeding, perforation)
Prevention of relapse
Approaches for treatment of peptic
ulcer
Reduction of Neutralisation
gastric acid of gastric
secretion acid(antacids)
Systemic Non-systemic
• Amoxicillin
ANTI • Clarithromycin
• Tetracycline
H-PYLORI • Metronidazole/tinidazole
MECHANISM OF ACID SECRETION
Physiological acid secretion
Parietal cells are main site of acid secretion in stomach
Hydrogen potassium pump secretes H+ ions in the apical
canaliculi of parietal cells by follwing secretogouges:
1. Histamine
2. Gastrin
3. Acetylcholine
DRUGS FOR REDUCTION OF GASTRIC
ACID SECRETION
secretion.
juice.
• S enantiomer of
More potent than
omeprazole . Newer PPI is claimed to
omeprazole .
• Similar potency and cause faster acid
• Higher bioavailability clinical efficacy to suppression.
Inhibition of
omeprazole ,but is more
H+K+ATPase is partly
• Slower elimination . acid stable and has higher Due to higher pKa,it is
reversible.
bioavailability. more rapidly converted
• Longer t1/2. to the active species.
Higher oral availability .
• Affinity for CYT P450 is
• Higher healing rates of lower than omeprazole or However ,potecy and
Faster onset of action
erosive esophagitis and lansoprazole:risk of drug efficacy are similar to
better GERD symptoms interactions is minimal. omeprazole .
Slightly longer t1/2 than
relief is reported.
omeprazole.
• Side effect and drug
Side effects are similar
interactions similar to •
but drug interactions are
racemic drug .
les significant .
USES
1. PEPTIC ULCER
3. STRESS ULCER
5. ZOLLINGER-ELLISON SYNDROME
6. ASPIRATION PNEUMONIA
PEPTIC ULCER
Omeprazole produces more complete round the clock inhibition of gastric acid
Higher dose than for peptic ulcer or twice daily administration is generally needed.
ZOLLINGER –ELLISON SYNDROME
syndrome .
Inoperable cases have been treated for >6 years with sustained hypersecretory
CIMETIDINE
RANTIDINE
FAMOTIDINE
ROXATIDINE
salts .
concentration.
ADVERSE EFFECT
Cimetidine is well tolerated ;adverse effects occur in <5%.
Mild side effects includes :
Headache ,dizziness ,bowel upset , dry mouth, rashes.
Cimetidine (not other h2 blockers) has –
I. Antiandrogenic action
II. Increases plasma prolactin
III. Inhibits degradation of estradiol by liver .
IV. High doses for prolong time causes gynaecomastia, loss of libido ,impotency
,temporary decrease in sperm count
INTERACTIONS
i. Cimetidine inhibits several cytochrome p450 enzyme and decreases hepatic blood flow .
ii. It is an enzyme inhibitor : inhibits metabolism of many drugs
a) Warfarin
b) Antipsychotics
c) Lidocaine
d) Nifedipine
e) Sulfonylurea
i. Antacids reduce absorption of all h2 blockers
ii. Ketoconazol absorption is decreased (reduced gastric acidity)
When used concurrently a gap of 2 hrs is required.
RANITIDINE FAMOTIDINE ROXATIDINE
• 5 times more potent. • Longer duration of action. • Twice as potent and longer
acting than ranitidine .
• Pharmacokinetic profile • Some inverse agonistic action
similar to cimetidine. on h2 receptor had been • Pharmacokinetic profile same
noted . as that of ranitidine.
• No antiandrogenic action
• 5-8 times more potent than • No anti androgenic action .
• No increase in prolactin ranitidine .
secretion • No cytochrome p450
• Antiandrogenic action absent. inhibitory action.
• Less marked effect on hepatic
metabolism. • Bioavailability 40-50%.
2. GASTRIC ULCERS
effects.
Prostaglandin Analogue
PGE2 and PGI2 are produced in the gastric mucosa.
DISADVANTAGE-
(a) Absorbed systemically: large doses will induce alkalosis.
(b) Produces CO2 in stomach
(c) Acid rebound occurs, but is usually short lasting.
(d) Increases Na+ load
USES OF SODIUM BICARBONATE-
Casual treatment of heartburn
Alkalinize urine
To treat acidosis
2. SODIUM CITRATE
Properties similar to sod. bicarbonate
CO2 is not evolved
NON-SYSTEMIC ANTACIDS
1.MAGNESIUM HYDROXIDE
Low water solubility
Its aqueous suspension (milk of magnesia) has low
concentration of OH¯ ions and thus low alkalinity.
Rebound acidity is mild and brief.
2. ALUMINIUM HYDROXIDE GEL
Constipation
Osteomalacia
Aluminium toxicity (encephalopathy, osteoporosis)
USES
Used therapeutically in hyperphosphatemia and phosphate
stones.
3. CALCIUM CARBONATE
Potent and rapidly acting acid neutralizer
DRAWBACKS-
Liberates CO2
Acid rebound occurs.
Mild constipation or rarely loose motions may be
produced.
The absorbed calcium can be dangerous in renal
insufficiency.
4. MAGALDRATE
It is a hydrated complex of hydroxymagnesium
aluminate that initially reacts rapidly with acid
and releases alum. hydroxide
Has prompt and sustained neutralizing action.
Antacid combinations
These may be superior to any single agent on the following
accounts:
Tetracyclines Phenothiazines
Iron salts Indomethacin
Fluoroquinolones Phenytoin
Ketoconazole Isoniazid
H2 blockers Ethambutol
Diazepam Nitrofurantoin
ULCER PROTECTIVE
It incluses sucralfate, colloidal bismuth subcitrate, rebamipide,
ecabet
Both mucus and epithelial Cell to cell tight junction restrict back
diffusion of acid and pepsin.
MECHANISM OF ACTION
Constipation
Hypophosphatemia
Dry mouth and nausea are infrequent
USES
DOSE:-
120mg taken 1/2 hour before 3 major meal and at bedtime for
4-8 weeks
Scientific contribution:-
- In 1940, Dr. A. Stone freedberg of Harvard medical school identified unusual curved shaped bacteria
in stomach of ulcers victim
MORPHOLOGY
H. pylori is spiral shaped gram negative bacteria.
It has a multiple polar flagella above the pole and motile.
It is a strong producer of urease.
UREASE
UREA CO2 + NH3
Adaptation to acidic environment of stomach
14 14
DAYS CBS 120mg
DAYS METRONIDAZOLE
QID 400mg TDS
OMEPRAZOLE TETRACYCLINE
20 mg BD 500 mg QID
• DAY 1-14 Amoxicillin1g BD PPIs 14 days
BD
• DAY 7-14 Clarithromycin 500 mg BD+metronidazole
500mg BD
• DAY 1-5 Amoxicillin 1g BD PPIs 10 days
BD
• DAY 6-10 Clarithromycin 500mgBD+metronidazole
500mg BD
SEQUENTIAL QUADRUPLE THERAPY
Active ulcer not attributable to H-pylori
Proton pump inhibitors
Uncomplicated duodenal ulcer: treat for 4 weeks
Uncomplicated gastric ulcer: treat for 8 weeks
H 2-receptor antagonists:
Uncomplicated duodenal ulcer: cimetidine 800 mg, ranitidine
or nizatidine 300 mg, famotidine 40 mg, orally OD at bedtime for 6
weeks
Uncomplicated gastric ulcer: cimetidine 400 mg, ranitidine or
nizatidine 150 mg, famotidine 20 mg, orally BD for 8 weeks
Complicated ulcers: proton pump inhibitors are the preferred drugs
Peptic ulcer disease
Lifestyle modifications
Diet management
Stop consumption of alcohol, NSAIDS
Stress management
Smoking cessation
Anti ulcer therapy
Drugs for peptic ulcer
1. REDUCTION OF GASTRIC ACID SECRETION
H2 antihistaminics
Proton pump inhibitors
Anticholinergic drugs
Prostaglandin analogues
2. ANTACIDS
Systemic
Non-systemic
3. ULCER PROTECTIVES
4. ANTI H. PYLORI DRUGS
DRUGS OF CHOICE