Drugs acting on the gastro-intestinal tract

1. INTRODUCTION

2. Drugs used in the GIT grouped in to the following
category basing on their effects.
 Antacids
 Laxatives
 Purgatives
 Antispasmodic/sedatives
 Ant diarrhoeas
 Carminative

3.  Emetics/ant emetics
 Digestant
 Diagnostic agent
 Sulphonamides
 Vermifuges

4.  Is usually a base or a basic salt which
counteract stomach acidity.
 Are basic substances that reduce
gastric acidity by neutralising HCL.

5. The stomach secretes:
 Hydrochloric acid (HCl)
 Bicarbonate
 Pepsinogen
 Intrinsic factor
 Mucus
 Prostaglandins

6.  HCl – an acid that aids digestion and also serves
as a barrier to infection
 Bicarbonate – a base that is a natural
mechanism to prevent hyperacidity
 Pepsinogen – an enzymatic precursor to pepsin,
an enzyme that digests dietary proteins

7.  Intrinsic factor – a glycoprotein that facilitates
gastric absorption of vitamin B12
 Mucus – protects the stomach lining from both
HCl and digestive enzymes
 Prostaglandins – serve a variety of anti-
inflammatory and protective functions

8.  Cardiac
 Pyloric
 Gastric
Note:The cells of the gastric gland are the largest in
number and of primary importance when
discussing acid control

9.  The stomach is divided into three functional areas,
each with specific glands.
 The cardiac zone(cells), the uppermost area of the
stomach by the cardiac sphincter, contains the
cardiac glands.
 The pyloric zone is the lowermost part of the
stomach and contains the pyloric glands.

10.  The greater part of the body of the stomach, the
fundus, contains the gastric glands.
 The gastric glands play the most significant role in
acid-related disorders.

11.  Parietal cells
◦Produce and secrete HCl
◦Primary site of action for many acid-
controller drugs

12.  Secreted by the parietal cells when
stimulated by food
 Maintains stomach at pH of 1 to 4
 Secretion also stimulated by:
◦Large fatty meals
◦Excessive amounts of alcohol
◦Emotional stress

13.  Chief cells
◦Secrete pepsinogen, a proenzyme
◦Pepsinogen becomes pepsin when
activated by exposure to acid
◦Pepsin breaks down proteins
(proteolytic)

14.  Mucoid cells
◦Mucus-secreting cells (surface
epithelial cells)
◦Provide a protective mucous coat
◦Protect against self-digestion by HCl

15.  Caused by imbalance of the three
cells of the gastric gland and their
secretions
 Most common: hyperacidity
 Clients report symptoms of
overproduction of HCl by the parietal
cells as indigestion, sour stomach,
heartburn, acid stomach

16.  PUD: peptic ulcer disease
 GERD: gastroesophageal reflux disease
 Helicobacter pylori (H. pylori)
◦ Bacterium found in GI tract of 90% of
patients with duodenal ulcers, and 70%
of those with gastric ulcers
◦ Combination therapy is used most often
to eradicate H. pylori

17.  There are three basic categories of
acid-controlling agents.
 Antacids – first developed by the
ancient Greeks who used crushed
coral (calcium carbonate) to treat
dyspepsia.

18.  H2 Antagonists - It wasn’t until the 1970s that a
new class of acid-controllling agent (H2 blockers)
was developed.
 Proton pump inhibitors

19.  They neutralise acid in the stomach by
chemical reaction, forming non acidic salt
and water, therefore rising the Ph of the
stomach.
• Stimulate mucosal Prostaglandins
production : prevent activation of proton
pump which results in ⇓ HCl production

20.  Antacid are used in treatment of heartburn and
symptomatic treatment of peptic ulcers disease.
Peptic ulcers disease (PUD), my involve lower
oesophagus, stomach and duodenum.

21.  Sodium bicarbonate NaHCO3
 Calcium carbonate CaCO3
 Al hydroxide Al(OH)3
 Magnesium Hydroxide
Mg(OH)2
 Magnesium trisilicate

23. Reduction of pain associated with acid-related
disorders
◦ Raising gastric pH from 1.3 to 1.6
neutralizes 50% of the gastric acid
◦ Raising gastric pH 1 point (1.3 to 2.3)
neutralizes 90% of the gastric acid
◦ Reducing acidity reduces pain
◦ Used alone or in combination

24.  Forms: carbonate, hydroxide
 Have constipating effects
 Often used with magnesium to counteract
constipation
 Examples
◦ Aluminum carbonate: Basaljel
◦ Hydroxide salt: AlternaGEL
◦ Combination products (aluminum and magnesium):
Gaviscon, Maalox, Mylanta, Di-Gel

25.  Forms: carbonate, hydroxide, oxide, trisilicate
 Commonly cause diarrhea; usually used with
other agents to counteract this effect
 Dangerous when used with renal failure —the
failing kidney cannot excrete extra magnesium,
resulting in hypermagnesemia

26.  Examples
◦ Hydroxide salt: magnesium hydroxide (MOM)
◦ Carbonate salt: Gaviscon (also a combination product)
◦ Combination products such as Maalox, Mylanta
(aluminum and magnesium)

27. Forms: many, but carbonate is most common
 May cause constipation
 Their use may result in kidney stones
 Long duration of acid action may cause increased
gastric acid secretion (hyperacidity rebound)
 Often advertised as an extra source of dietary
calcium
◦ Example: Tums (calcium carbonate)

28.  Highly soluble
 Buffers the acidic properties of HCl
 Quick onset, but short duration
 May cause metabolic alkalosis
 Sodium content may cause problems in patients
with Heart Falure , hypertension, or renal
insufficiency (fluid retention)

29. OTC antiflatulents
 Activated charcoal
 Simethicone
◦ Alters elasticity of mucus-coated
bubbles, causing them to break
◦ Used often, but there are limited data to
support effectiveness

31.  Gastric acid secretion by parietal cells of the
gastric mucosa is stimulated by acetylcholine,
histamine, and gastrin.
 The receptor-mediated binding of acetylcholine,
histamine, or gastrin results in the activation of
protein kinases, which in turn stimulates the
H+/K+–adenosine triphosphatase (ATPase)
proton pump to secrete hydrogen ions in
exchange for K+ into the lumen of the stomach.

32.  Reduce acid secretion
 Most popular drugs for treatment of acid-related
disorders
◦ cimetidine
◦ famotidine
◦ ranitidine

33.  Antagonists of the histamine H2 receptor block the
actions of histamine at all H2 receptors,
 Their chief clinical use is to inhibit gastric acid
secretion, being particularly effective against
nocturnal acid secretion.
 By competitively blocking the binding of histamine to
H2 receptors, these agent reduce the intracellular
concentrations of cyclic adenosine monophosphate
and, thereby, secretion of gastric acid.

34.  GERD (gastroesophageal reflux disease)
 PUD
 Erosive esophagitis
 Adjunct therapy in control of upper GI bleeding
 Pathologic gastric hypersecretory conditions
(Zollinger-Ellison syndrome)

35.  Cimetidine may induce impotence and
gynecomastia in males
 Other effects
◦ Headaches, lethargy, confusion, diarrhea, urticaria,
sweating, flushing, Dizziness
 Due to the mention above side effects cimetidine
is largely replaced by Ranitidine which have less
side effects with relatively similar potency.

37.  The parietal cells release positive hydrogen ions
(protons) during HCl production
 This process is called the “proton pump”
 H2 blockers and antihistamines do not stop the
action of this pump
 Proton pump is the terminal step in acid secretory
pathway.
 Drugs in this group are usually taken once a day

39.  The action of the hydrogen-potassium-ATPase
pump is the final step in the acid-secretion
process of the parietal cell.
 If the chemical energy is present to run the pump
it will transport the hydrogen ions out of the
parietal cell, which increases the acid content of
surrounding gastric lumen and lowers the pH.

40.  Hydrogen ions are protons (positively charged
hydrogen atoms) this ion pump is also called the
proton pump.
 The PPI bind irreversibly to the proton pump.
 The binding of this enzyme prevents the
movement of the hydrogen ion out of the parietal
cells into the stomach and therefore blocks all acid

41.  PPI effectively stop over 90% of acid production
in the stomach. For acid secretion to return to
normal after the pt. stops the PPI the parietal cell
must synthesize new hydrogen potassium
productionATPase.

42.  Reduce gastric acid secretion by inhibiting the
action of H+
/K+
ATPase enzyme
 Irreversibly bind to H+
/K+
ATPase enzyme
 Result: achlorhydria—ALL gastric acid secretion is
blocked

43.  Total inhibition of gastric acid secretion
 Proton pump includes:
◦ lansoprazole 30mg daily for four weeks
◦ omeprazole 20mg daily for four weeks
◦ rabeprazole
◦ pantoprazole
◦ esomeprazole

44.  GERD maintenance therapy
 Erosive esophagitis
 Short-term treatment of active duodenal and
benign gastric ulcers
 Zollinger-Ellison syndrome
 Treatment of H. pylori–induced ulcers

45.  Headache
 Rashes
 Pain in muscles and joints
 Diarrhoea and impotency in male may also occur
 Prolonged use leads to vitamin B12 deficiency
(because HCl is important for releasing vitamin
B12 from food).

46.  These agents are also known as cytoprotectives.
 They prevent damaged mucosa from acid in the
stomach. Some cytoprotectives acts by forming a
gel with mucus therefore preventing acid from
reaching stomach or duodinal ulcers.

47.  Cytoprotectives include:
 Bismuth chelate
 Misoprostol
 sucralfate

48.  Bismuth chelate (tripotassium
dicitratobismuthate) this have another
advantage that it also inhibit growth of bacilli
therefore can be used in combination with other
drugs to treat Helicobacter pylori
 it is given at the dose of 10ml twice daily or 5ml
four times a day for four weeks

49. Pharmacological actions:
1- Undergoes rapid dissolution in the stomach into
bismuth and salicylates.
2- Salicylates are absorbed
3- Bismuth coats ulcers and erosions protecting
them from acid and pepsin and increases
prostaglandin and bicarbonate production
Uses:
-Treatment of dyspepsia and acute diarrhoea

50. Sucralfate = complex aluminum hydroxide +
sulfate + sucrose
Mechanism of action:
1- in acidic environment of the stomach, it forms a
viscous paste that binds to ulcers or erosions for
6 hours forming a physical barrier against
hydrolysis of mucosal proteins by pepsin.

51. 2- stimulates mucosal prostaglandins and
bicarbonate production
3- Sucralfate binds bile salts (used to treat
individuals with biliary gastritis

52.  Used for stress ulcers, erosions, PUD
 Attracted to and binds to the base of ulcers and
erosions, forming a protective barrier over these
areas
 Protects these areas from pepsin, which normally
breaks down proteins (making ulcers worse)

53.  Sucralfate is given at the dose of 2g twice a day.
 The drug have disadvantage that it inhibit
absorption of various drugs including
fluoroquinolon antibiotics(Ciprofloxacin,
penfloxacin, norfloxacin etc), tetracycline,
theophylline and amitryptylline, Digoxin,
Phenytoin.


54.  Adverse Effects:
Constipation
 Precautions:
1) should be avoided in patients with renal failure
(because some aluminium is absorbed).
2) Should be taken at least 2 hours after the
administration of other drugs as phenytoin and
digoxin (forms a viscous layer in the stomach that
may inhibit absorption of drugs)

55.  Synthetic prostaglandin analog
 Prostaglandins have cytoprotective activity
◦ Protect gastric mucosa from injury by enhancing local
production of mucus or bicarbonate
◦ Promote local cell regeneration
◦ Help to maintain mucosal blood flow
◦ Inhibit histamine-stimulated gastric acid secretion

56.  Used for prevention of NSAID-induced gastric
ulcers
 Doses that are therapeutic enough to treat
duodenal ulcers often produce abdominal cramps,
diarrhea

57.  Adverse Effects:
1. Diarrhea, with or without abdominal pain and
2. Exacerbations of inflammatory bowel disease and
should be avoided in patients with this disorder.

58. Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)

59. Gastro-esophageal
reflux disease
1- Mild: H2 receptor antagonists (twice daily)
2- Severe: Proton pump inhibitors once daily (for 8
weeks)
3- Antacids are recommended only for the patient with
mild, infrequent episodes of heartburn.
4- Severe with nocturnal acid breakthrough: proton
pump inhibitors twice daily. If symptom persist, H2
receptor antagonist is added at night
Helicobacter pylori
infection (H. pylori)
Triple therapy for 14 days:
[Proton pump inhibitor + clarithromycin 500 mg +
(metronidazole 500 mg or amoxicillin 1 g)] twice a day.
NSAID-related Ulcers 1- Proton pump inhibitors (best)
2- H2 receptor antagonist
3- Misoprostil
Peptic ulcer Proton pump inhibitors