DRUGS USED IN ACID

PEPTIC
DISEASES
 Acid-peptic diseases include:-

 gastroesophageal reflux
 peptic ulcer (gastric and duodenal)
 stress-related mucosal injury.

In all these conditions, mucosal erosions or

ulceration, and the processes of restitution and
regeneration after cellular injury). Over
 Acid-peptic diseases arise when the
caustic effects of aggressive factors
overwhelm the defensive factors of the
gastrointestinal mucosa
 aggressive factors like :-
 Acid
 Pepsin
 Bile
defensive factors of the gastrointestinal
mucosa
 mucus

 bicarbonate secretion

 Prostaglandins

 blood flow

 90% of peptic ulcers are caused by

 infection with the bacterium Helicobacter
pylori
 use of nonsteroidal anti-inflammatory
drugs (NSAIDs).
 Treatment of acid peptic
disorder :-
 Drugs used in the treatment of acid-peptic
disorders may be divided into two classes:

1) agents that reduce intragastric acidity

 ANTACIDS

 H 2 -RECEPTOR ANTAGONISTS

 PROTON PUMP INHIBITORS

2 ) agents that promote mucosal
defense.
SUCRALFATE
PROSTAGLANDIN ANALOGS
BISMUTH COMPOUNDS
AGENTS THAT
REDUCE
INTRAGASTRIC
ACIDITY
 PHYSIOLOGY OF ACID
SECRETION
 Parietal cells are stimulated to secrete acid
(H + ) by:-
 gastrin (acting on gastrin/CCK-B receptor)
 acetylcholine (M 3 receptor)
 histamine (H 2receptor).
 Acid is secreted across the parietal cell
canalicular membrane by the H + /K + -
ATPase proton pump into the gastric lumen.
 Gastrin is secreted by antral G cells into blood
binds to gastrin-CCK-B receptors on parietal
cells and enterochromaffin-like (ECL) cells.
 The enteric nervous system release
acetylcholine (ACh), which binds to M 3
receptors on parietal cells and ECL cells.
 Stimulation of ECL cells by gastrin (CCK-B
receptor) or acetylcholine (M 3 receptor)
stimulates release of histamine.
 Histamine binds to the H 2 receptor on the
parietal cell, resulting in acid secretion by the
H + /K + - ATPase.
 1) ANTACIDS

 Antacids have been used for centuries in the

treatment of patients with dyspepsia and acid-peptic
disorders.
 commonly used by patients as nonprescription
remedies for the treatment of intermittent heartburn.
 Their principal mechanism of action is reduction of
intragastric acidity by react gastric hydrochloric acid
to form a salt and water (Antacids are weak bases).
 Antacid available are:- Sodium bicarbonate ,
Calcium carbonate, magnesium hydroxide and
aluminum hydroxide
 All antacids may affect the absorption of other
medications by binding the drug
 2 ) H 2 -RECEPTOR
ANTAGONISTS
 H 2 - receptor antagonists (commonly
referred to as H 2 blockers) were the most
commonly prescribed drugs in the world.
 the advent of proton pump inhibitors, the
use of prescription H 2 blockers has
declined markedly.
 Four H 2 antagonists are in clinical use:
cimetidine, ranitidine, famotidine, and
Nizatidine.
 Mechanism of action :-
 the four H 2 -receptor antagonists when
given in usual prescription inhibit 60–
70% of total 24-hour acid secretion.
 H 2 antagonists reduce acid secretion
by block histamine (released from ECL
cells ) from binding to the parietal cell H
2 receptor.
 Clinical Uses:-

A. Gastroesophageal Reflux Disease

(GERD)
B. Peptic Ulcer Disease
C. Nonulcer Dyspepsia
 Adverse Effects
 H 2 antagonists are extremely safe drugs.
Adverse effects occur in less than 3% of
patients and include diarrhea, headache,
fatigue, myalgias, and constipation.
 cimetidine When used long-term or in high
doses, it
may cause gynecomastia or impotence in men
and galactorrhea in women.
 PROTON PUMP
INHIBITORS:-
 Six proton pump inhibitors are available
for clinical use: omeprazole,
esomeprazole, lansoprazole,
dexlansoprazole, Rabeprazole, and
pantoprazole.
 Proton pump inhibitors are administered
as inactive prodrugs.
 Mechanism of action
 proton pump inhibitors inhibit acid
secretion because they block the final
common pathway of acid secretion, the
proton pump.
 In standard doses, proton pump inhibitors
inhibit 90–98% of 24-hour acid secretion
 A) Gastroesophageal Reflux Disease (GERD)
patients with symptomatic GERD are treated empirically
with medications without knowledge of whether the patient
has erosive or nonerosive reflux disease.
B ) Peptic Ulcer Disease
1. H pylori-associated ulcers—
 For H pylori -associated ulcers, there are two
therapeutic goals:
to heal the ulcer
to eradicate the organism.
The most effective regimens for H pylori eradication are
combinations of two antibiotics and a proton pump
inhibitor. Proton pump inhibitors
 The best treatment regimen consists of a
14-day regimen of “triple therapy”: -
 a proton pump inhibitor twice daily
 clarithromycin, 500 mg twice daily.
 amoxicillin, 1 g twice daily, or
metronidazole, 500 mg twice daily.
 After completion of triple therapy, the
proton pump inhibitor should be
continued once daily for a total of 4–6
weeks to ensure complete ulcer healing.
 Alternatively, 10 days of “sequential
treatment” consisting on
 days 1–5 of a proton pump inhibitor
twice daily plus amoxicillin, 1 g
twice daily.
 followed on
 days 6–10 by five additional days of
a proton pump inhibitor twice daily,
plus clarithromycin, 500 mg twice
daily, and Tinidazole, 500 mg twice
daily
2 -NSAID-associated ulcers—
 Proton pump inhibitors provide rapid

ulcer healing so long as the NSAID is

discontinued.
 In patients with NSAID-induced

ulcers who require continued NSAID

therapy, treatment with a once- or
twice-daily proton pump inhibitor
more reliably promotes ulcer healing
C ) Prevention of Stress-Related
Mucosal Bleeding
The only proton pump inhibitor approved
by the Food and Drug Administration (FDA)
for this indication is an oral immediate-
release omeprazole formulation
MUCOSAL
PROTECTIVE
AGENTS
 The gastro duodenal mucosa has evolved a
number of defense mechanisms to protect
itself against the noxious effects of acid and
pepsin
 mucus restrict back diffusion of acid and
pepsin
 Epithelial bicarbonate secretion establishes
a pH gradient within the mucous layer
 Blood flow carries bicarbonate and vital
nutrients to surface cells and provide quickly
repaired to areas of injured epithelium.
 Mucosal prostaglandins appear to be
important in stimulating mucus and
bicarbonate secretion and mucosal
blood flow.
 factors interfere with the mucosa
protective mechanisms:-

 Use of non-steroidal anti inflammatory

drug (NSAIDs)
 Cigarette smoking, stress
 Frequently fasting for long time
 Alcohol
 Presence of bacteria called Helicobacter
pylori in the stomach
 1) SUCRALFATE
 Sacrulfate is a salt of sucrose complexed to
sulfated aluminum hydroxide.
 In water or acidic solutions it forms a viscous,
tenacious paste.
 the precise mechanism of action is unclear.
 It is believed that the negatively charged sucrose
sulfate binds to positively charged proteins in the
base of ulcers or erosion, forming a physical
barrier
 Sacrulfate is still used by many clinicians for
prevention of stress-related bleeding.
 Constipation occurs in 2% of patients due to the
aluminum salt.
 2) BISMUTH COMPOUNDS
 Two bismuth compounds are available: bismuth
subsalicylate and bismuth subcitrate
potassium.
 The precise mechanisms of action of bismuth are
unknown.
 Bismuth coats ulcers and erosions, creating a
protective layer against acid and pepsin.
 Bismuth subsalicylate reduces stool frequency
and liquidity in acute infectious diarrhea.
 bismuth subcitrate potassium widely used by
patients for the nonspecific treatment of
dyspepsia.
  Bismuth compounds are used in 4-drug
regimens for the eradication of H pylori
infection
1. pump inhibitor twice daily combined with
bismuth subsalicylate (2 tablets; 262 mg
each)
2. tetracycline (250–500 mg).
3. Metronidazole (500 mg) four times daily for
10–14 days
 Bismuth causes harmless blackening of the
stool,
 PROSTAGLANDIN
ANALOGS:-
 The human gastrointestinal mucosa
synthesizes a number of prostaglandins
 the primary ones are prostaglandins E
and F. Misoprostol,
 A analog of PGE 1 , has been approved
for gastrointestinal conditions.
 Misoprostol has both acid inhibitory and
mucosal protective properties.
 It is stimulate mucus and bicarbonate secretion
 enhance mucosal blood flow.
 it binds to a prostaglandin receptor on parietal
cells, reducing histamine-stimulated acid inhibition.
 It is approved for prevention of NSAID-induced
ulcers in high-risk patients.
 Diarrhea and cramping abdominal pain occur in 10–
20% of patients.
 Because misoprostol stimulates uterine
contractions it should not be used during
pregnancy.
DRUGS STIMULATING
GASTROINTESTINAL
MOTILITY
 Drugs that can selectively stimulate gut motor
have significant potential clinical usefulness.
 Prokinitic drugs :-
1. Agents that increase lower esophageal sphincter
pressures may be useful for GERD.
2. Drugs that improve gastric emptying may be
helpful for gastro paresis and postsurgical
gastric emptying delay.
 Laxative :-
agents that enhance colonic transit may be useful
in the treatment of constipation.
 Prokinitic drugs :-

 METOCLOPRAMIDE & DOMPERIDONE

 MACROLIDES
 CHOLINOMIMETIC AGENTS
 METOCLOPRAMIDE &
DOMPERIDONE

 Metoclopramide and dopmeridone are

dopamine D 2 –receptor antagonists.
 Within the gastrointestinal tract activation
of dopamine receptors inhibits cholinergic
smooth muscle stimulation; blockade of
this effect is believed to be the primary
prokinetic mechanism of action of these
agents.
 Clinical Uses
 Gastroesophageal Reflux Disease.
 Prevention of Vomiting.
 Postpartum Lactation Stimulation

Adverse effect :-
 The most common adverse effects of metoclopramide
involve the central nervous system. Restlessness,
drowsiness, insomnia, anxiety.

 Dopmeridone is extremely well tolerated. Because it

does not cross the blood-brain barrier to a significant
degree
LAXATIVES
 The overwhelming majority of people
do not need laxatives; yet they are
self-prescribed by a large portion of
the population
 Laxative are medicines accelerate the
passage of food through the intestine.
 For most people, intermittent
constipation is best prevented with :-
1. high-fiber diet
2. adequate fluid intake
3. regular exercise.
 Laxatives are generally of value in:
1. Treatment of drug-induced constipation,
for the expulsion of parasites after
antihelminthic treatment
2. Clear the alimentary canal before
surgery or radiological procedures
 Laxatives of any type should not be used
when there is obstruction of the bowel
 Overuse can lead to an atonic colon
where the natural propulsive activity is
diminished
 When drug treatment is required, bulking
agents are the first choice, followed by
the osmotic laxatives
 Stimulant drugs are reserved for
intermittent use only
Classification of laxatives:-
 Laxatives may be classified by their
major mechanism of action, in to :-
 BULK-FORMING LAXATIVES
 STOOL SURFACTANT AGENTS
(SOFTENERS)
 OSMOTIC LAXATIVES
 STIMULANT LAXATIVES
 BULK-FORMING LAXATIVES

 Common preparations include

natural plant products ( methylcellulose )
synthetic fibers (polycarbophil).
 Bulk-forming laxatives are indigestible,

hydrophilic colloids .
 they absorb water, forming a bulky,
emollient gel that distends the colon and
promotes peristalsis.
 STOOL SURFACTANT AGENTS
(SOFTENERS)
 Common agents include docusate (oral or
enema) and glycerin suppository,
mineral oil .
 These agents soften stool material,
permitting water and lipids to penetrate.
 viscous oil that lubricates fecal material,
retarding water absorption from the stool.
 OSMOTIC LAXATIVES

 Osmotic laxatives are soluble but

nonabsorbable compounds that result in
increased stool liquidity due to an obligate
increase in fecal fluid.
 Nonabsorbable Sugars or Salts(Magnesium
hydroxide (milk of magnesia)) is commonly
used osomatic laxative
 lactulose are nonabsorbable sugars that can
be used to prevent or treat chronic
constipation. These sugars are metabolized by
colonic bacteria, producing severe flatus and
cramp
 polyethylene glycol (PEG) are used for
complete colonic cleansing before
gastrointestinal endoscopic procedures.
 STIMULANT LAXATIVES

 Stimulant laxatives (cathartics) induce

bowel movements through direct
stimulation of the enteric nervous system
and colonic electrolyte and fluid
secretion.
 Anthraquinone Derivatives(Aloe,
Senna)
 Diphenylmethane Derivatives
(Bisacodyl)