Gastrointestinal Agents covers about Peptic Ulcer, Alcoholic Liver Diseases, GERD and Inflammatory Bowel Disease

1.  Gastro oesophageal reflux disease
 Peptic Ulcer Disease
 Alcoholic liver disease
 Inflammatory Bowel Diseases (Crohn’s Disease and Ulcerative
Colitis)
GASTROINTESTINAL
DISORDER

2.  The term gastrointestinal disorders refer to any condition or
disease that occurs within the gastrointestinal tract. For
example, gastro esophageal reflux disease (GERD), peptic
ulcer disease (PUD), alcoholic liver disease (ALD),
inflammatory bowel disease (IBD), etc.
 Gastrointestinal tract includes the mouth, esophagus,
stomach, small intestine, large intestine, colon, rectum,
biliary tract, gallbladder, liver, and pancreas.
INTRODUCTION

3.  Gastro esophageal reflux disease (GERD) is a chronic
condition in which gastric content flow back into the
esophagus, causing irritation to the esophageal mucosa with
or without tissue damage.
 The GERD with tissue damage is known as esophagitis or
erosion GERD and without tissue damage is known as non-
erosive reflux disease (NERD)
GASTRO ESOPHAGEAL REFLUX DISEASE
(GERD)

4. Risk Factors Linked to GERD:
 Age and male sex are associated with a higher incidence of
esophagitis.
 Obesity - Obese people 2.5 times more likely to have GERD
than those with normal body mass index (BMI).
 Alcohol consumption
 Stress
 Smoking
 Coffee, chocolate, acidic and fatty foods (e.g. spicy foods,
citrus, carbonated drinks
 Certain eating habits (e.g., heavy meals or lying down shortly
after eating)
ETIOPATHOGENESIS OF GERD

5.  Hiatal hernia (It is a condition in which part of the stomach
pushes up through the diaphragm muscle).
 Medication. A number of common drugs are associated with
GERD e.g. Anticholinergic, benzodiazepines, calcium channel
blockers, dopamine, nicotine nitrates, theophylline, estrogens,
progesterone, glucagon, some prostaglandin, NSAIDs,
bisphosphonates, antibiotics, etc.
 Pregnancy
 Gastrointestinal malformations and tumors
 latrogenic (e.g. after gastrectomy)
 Scleroderma
 Infectious esophagitis
 Asthma

6.  The various mechanisms involved in the production of
gastroesophageal reflux are inappropriate, transient
relaxation of the lower esophageal sphincter (LES), pressure
abnormalities in the LES (due to hormonal and neural
mediators, food, drugs and patient lifestyle), poor esophageal
clearance, delayed gastric emptying time and hiatal hernia.
 Untreated GERD may lead to Barrett esophagus, esophagitis,
ulceration, stricture, and rarely adenocarcinoma (An
esophageal stricture is an abnormal tightening of the
esophagus)

7. Clinical manifestations of GERD can be classified as esophageal and
extraesophageal manifestations of GERD.
(A) Esophageal (Typical) Manifestations
 Retrosternal pain (Heart burn)
 Chest pain
 Epigastric pain
 Regurgitation mostly after meals
 Dysphagia (difficulty or discomfort in swallowing)
 Odynophagia (Painful swallowing)
 Nausea
 Belching
 Early satiety
 Bloating
 Water brash (Excessive salivation)
 Halitosis (Bad breath)
CLINICAL MANIFESTATIONS OF GERD

8. (B) Extraesophageal (Atypical) Manifestations
 Chronic cough
 Asthma
 Laryngitis
 Bronchospasm
 Recurrent pulmonary infections
 Otitis media
 Dental erosion
 Discomfort in the nose
 Trouble sleeping

9. Diagnosis and Investigation of GERD
 A diagnosis of GERD based on the presence of typical symptoms
is correct in only 70% of patients.
 Diagnostic studies, e.g, upper GI endoscopy, esophageal
manometry test, 24-hours pH probe test and nuclear medicine
gastric emptying study, may be indicated to confirm the
diagnosis or to rule out other causes of symptoms.

10.  The goals of GERD treatment are to control symptoms, to heal
esophagitis, and prevent recurrent esophagitis or other
complications.
 The treatment of GERD consists of lifestyle modification and
initiating acid suppression therapy, preferably with proton
pump inhibitors (PPIs).
 Sometimes surgical treatment with corrective anti reflux
surgery is considered in select cases, e.g, patients who
develop complications despite receiving optimal drug therapy.
 Patients with signs of GERD complications or other illness or
do not respond to drug therapy should be considered for
further diagnostic testing
MANAGEMENT OF GERD

11.  Non-pharmacological management of GERD includes patient
education, lifestyle modification and surgical therapy.
 All patients should be educated regarding factors that may
worsen the symptoms.
 Lifestyle modification is considered to be the first line of
treatment of GERD.
 Lifestyle modification includes
 Avoid alcohol, chocolate, citrus juice, and tomato-based products.
 Weight loss (if overweight)
 Avoid peppermint, coffee, and possibly the onion family
 Avoid smoking
 Avoid eating at least 3 hours before bedtime, elevating the head of the
bed
 Avoid skipping meals
 Avoid drugs that lower LES pressure [e.g., calcium channel blockers, beta
alpha-adrenergic agonists, theophylline, nitrates, PDE-S inhibitors) or in
esophagus (e.g, Ferrous sulfate, NSAIDs, bisphosphonates, etc.)
NON-PHARMACOLOGICAL MANAGEMENT
OF GERD

12.  PPI drugs Cap. Omeprazole 20 mg once a day/BD OR
Rabeprazole 20 mg or Pantoprazole 40 mg once a day OR
Esomeprazole 40 mg once a Lansoprazole 30 mg once a day.
 All taken 30-60 minutes before meals for 2-8 weeks.
 Prokinetic agent Domperidone 30 mg sustained release. Other
prokinetic agents that can be used are Metoclopramide,
Itopride and Mosapride.
 PPIs irreversibly bind the proton pumps (H+/K+ ATPase), the
final step in gastric acid secretion.
 Side effects with PPIs are generally well tolerated and minor
such as diarrhea, abdominal pain, headache which resolves as
treatment is discontinued.
 Other option include to suppress acid secretion is H₂ receptor
antagonist e.g. Ranitidine, Cimetidine, Famotidine, Nizatidine,
Roxatidine may be given intermittently to patients intolerant
of PPIs.
PHARMACOLOGICAL MANAGEMENT OF
GERD

13.  Antacids and alginates are effective in short-
term or intermittent symptom antacid-alginate
combination is recommended for episodic and
postprandial symptoms.
 These preparations are usually taken after each
meal and at bed time Further evaluation may
be considered in patients non-responsive to
this therapy include an upper Gl endoscopy with
or without enhanced imaging and function
testing.

14. PEPTIC ULCER DISEASE

15.  Peptic ulcer disease is the presence of ulceration (an erosion
or lesion) in the esophagus, stomach, and duodenum
secondary due to pepsin and gastric acid secretion.
 The diameter of peptic ulcer is at least 0.5 cm and a depth
that reaches the muscularis mucosae.
 Peptic ulcer is the main cause of upper gastrointestinal
haemorrhage.
INTRODUCTION

16. Types of peptic ulcer are
 (A) According to site of ulcer
 1. Gastric ulcer (Stomach ulcer): It is a peptic ulcer of the gastric mucosa.
 2 Duodenal ulcer: It is a peptic ulcer of the duodenal mucosa
 (B) According to cause
 1. Helicobacter pylori associated peptic ulcers
 2 NSAID induced peptic ulcers

17.  Ulcer formation occurs when either the gastric protective
mechanisms are disrupt and/or excessive acids or pepsin is
secreted. The lining of the stomach and duodenum normally
has a barrier of mucous to protect it from acidic digestive
juices. If this protect barrier is damaged, the acid may cause
inflammation and lesion of the lining.
ETIOPATHOGENESIS OF PEPTIC ULCER

18.  Peptic ulcer disease (PUD) may be due to any of the following
 Helicobacter pylori infection (most common)
 Prolonged nonselective NSAID use (possibly in combination
with glucocorticoids)
 Medications such as steroids, SSRI, bisphosphonates,
anticoagulants, potassium chloride or chemotherapeutic
agents
 Lifestyle factors (e.g, alcohol use, smoking, caffeine, spicy
food, etc.).
 Psychological factors (e.g, anxiety, stress, post-traumatic
stress disorder (PTSD)

19.  Stomach cancer
 Extensive burns (e.g, Curling's ulcer)
 Increased intracranial pressure (e.g, Cushing's ulcer)
 Conditions associated with an overproduction of stomach acid
(hypersecretastates) (e.g. Zollinger-Ellison syndrome)
 Genetic factors
 Rarely systemic mastocytosis, hyperparathyroidism, radiation,
systemic inflammation diseases (e.g, Crohn's disease,
sarcoidosis)

20.  Epigastric pain is the most common symptom of peptic ulcer
but occurs only in minority of patients. It is characterized by a
gnawing or burning sensation. Pain typically follows a daily
pattern specific to the patient.
 In case of gastric ulcer. Pain increases shortly after eating,
there is a possibility of weight loss due to fear of food intake
and nightly pain is less common.
 In case of duodenal ulcer Pain increases 2-5 hours after
eating, pain is relieved with food intake, there is a possibility
of weight gain and nightly pain is more common.
 Other symptoms include belching, indigestion,
gastrointestinal reflux, nausea and vomiting, loss of appetite,
abdominal fullness, inability to tolerate fatty foods and
heartburn
CLINICAL MANIFESTATIONS OF PEPTIC
ULCER

21.  In advance cases upper abdominal pain, anorexia, cachexia.
 Hematemesis, melena, or anemia may suggest bleeding.
 Patient may show iron deficiency anaemia.
 Up to 70% of patients with peptic ulcers do not experience
symptoms.
Diagnosis and Investigation of Peptic Ulcer
 Stool Antigen Test
 Polymerase Chain Reaction (PCR)
 Urea breath test
 Biopsy
 CBC
 Liver Function Test
 GI Endoscopy

22. Drugs Dose (mg) Frequency Duration
Proton Pump Inhibitors (PPI) 20 mg BD 14 Days
Clarithromycin 500 mg BD
Metronidazole 400 mg BD
PI 20 mg BD 14 Days
Amoxicillin 1 mg BD
Metronidazole 400 mg TDS
PPI 20 mg BD 14 Days
Amoxicillin 1 mg BD
Clarithromycin 500 mg BD
PHARMACOLOGICAL MANAGEMENT OF
PEPTIC ULCER
H. Pylori Eradication Therapy

23. Proton Pump Inhibitor Oral Dose Frequency
Omeprazole 20 mg Twice Daily
Lansoprazole 30 mg Twice Daily
Pantoprazole 40 mg Twice Daily
Esomeprazole 20 mg Twice Daily
Rabeprazole 20 mg Twice Daily
Proton Pump Inhibitors

24. Oral Drug Regimens Used to Treat NSAID Induced Peptic Ulcers
Drug Oral Dose
Proton Pump Inhibitors
Omeprazole 20-40 mg daily
Lansoprazole 15-30 mg daily
Pantoprazole 40 mg daily
Esomeprazole 20-40 mg daily
Rabeprazole 20 mg daily
H2 Receptor Antagonists
Ranitidine 150 mg twice daily/ 300 mg at bed time
Famotidine 20 mg twice daily/ 40 mg at bed time
Ulcer Protective (Cytoprotective Agent)
Sucralfate 1 g four times daily/2 g twice daily

25.  Proton Pump Inhibitors
 H2 Receptor Antagonists
 Ulcer Protective

26. ALCOHOLIC LIVER DISEASE (ALD)

27.  Alcoholic liver disease (ALD) refers to a range of progressive
liver damaging conditions caused by chronic and excessive
alcohol consumption.
 Liver is the primary site for ethanol metabolism. Each time
liver filters alcohol, some of its cells die. The liver can
regenerate new cells, but chronic and excessive alcohol
consumption an reduce its ability to regenerate. This can
result in serious and permanent damage to the liver.
INTRODUCTION

28.  Chronic and excessive alcohol consumption produces a wide
spectrum of hepatic lesions which are steatosis, hepatitis,
fibrosis/cirrhosis and hepatocellular carcinoma.
 Steatosis is characterized by the deposition of fat in
hepatocytes Steatosis can progress to steatohepatitis, which
is a more severe, inflammatory type of liver injury.
ETIOPATHOGENESIS OF ALCOHOLIC LIVER
DISEASE (ALD)
 Steatohepatitis can lead to the
development of fibrosis, during
which there is excessive deposition
of extracellular matrix proteins This
stage may progress to cirrhosis,
characterized by excessive liver
scarring, vascular alterations, and
eventual liver failure.

29. The three stages of ALD, which may or may not occur
sequentially, are as follows:
 Stage I Alcoholic fatty liver: This is the stage of steatosis This
stage occurs after acute alcohol ingestion, is typically
asymptomatic and reversible with abstinence.
 Stage II Alcoholic hepatitis: This is the stage of
steatohepatitis Alcoholic hepatitis can range in severity from
asymptomatic to liver failure and death.
 Stage III Alcohol-related cirrhosis: This is the final stage of
ALD This stage involves replacement of the normal hepatic
parenchyma with extensive thick bands of fibrous tissue and
regenerative nodules, which results in the clinical
manifestations of portal hypertension and liver failure.

30.  The mechanism of development of ALD involves hepatic
degradation of ethanol to acetyl-CoA by alcohol
dehydrogenase results in excess of NADH.
 The excess of NADH drives the formation of glycerol 3-
phosphate (G3P) from dihydroxyacetone phosphate (DHAP
Increase in both G3P and fatty acids cause increased
triglyceride synthesis in the live accompanying inflammation
(steatohepatitis).
 Chronic inflammation leads to hepatic fibrosis and sclerosis
leading to portal hypertension and eventually cirrhosis.
PATHOGENESIS OF ALD

31.  Cofactors in the development of alcoholic liver disease (ALD)
are
 Genetic factors: Rate of alcohol metabolism plays a role
 Gender: Women are more susceptible compared to men
 Diet and nutrition: Under nutrition and over nutrition
 Cigarette smoking
 Co-morbid conditions e.g. Non-alcoholic steatohepatitis (NASH), non-
alcoholic fatty liver disease (NAFLD) viral hepatitis and
hemochromatosis

32.  1. Alcoholic fatty liver
 It is reversible
 Mostly asymptomatic
 Feeling a sensation of pressure in the upper abdominal area
 Hepatomegaly soft in consistency
 Acute exacerbation with risk of hepatic failure is rare
 2. Alcoholic hepatitis
 It is reversible in mild cases
 Nausea, loss of appetite, weight loss, low-grade fever with
tachycardia
 Hepatomegaly with hepatic tenderness
 Jaundice, fatigue, and fever
 If portal hypertension ensues, splenomegaly, ascites, and/or variceal
bleeding may develop
CLINICAL MANIFESTATIONS OF
ALCOHOLIC LIVER DISEASE (ALD)

33.  3. Alcohol-related cirrhosis
 It is irreversible and final stage of ALD
 Patients are often initially asymptomatic
 Nausea, vomiting, fatigue, malaise, anorexia, and weight loss
 Hepatomegaly
 Splenomegaly
 Pruritus
 Jaundice
 Ascites
 Telangiectasia (These are dilated small blood vessels on the skin or
mucous membranes)
 Caput medusa (It is the cluster of swollen veins in abdomen).
 Palmar erythema (It is a skin condition that makes the palms of
hands turn red)
 Petechiae and purpura
 Hormonal disorders
 Gynecomastia
 Hypogonadism
 Peripheral edema

34.  Patient history of habitual alcohol intake of sufficient length and
intensity, transaminase levels, and imaging studies are crucial
for diagnosis of ALD.
 Laboratory tests
 Aspartate aminotransferase (AST) > Alanine aminotransferase
(ALT) (both ↑ AST and ↑ ALT)
 ↑ Gamma-glutamyl transpeptidase (GGT)
 ↑ Serum ferritin
 ↑ CDT(carbohydrate-deficient transferring)
 ↑ Bilirubin
 ↑ Prothrombin time
 ↑ Glutamate dehydrogenase (GLDH)
 ↑ Ammonia
 ↓ Serum albumin
 ↓Cholinesterase
DIAGNOSIS AND INVESTIGATION OF
ALCOHOLIC LIVER DISEASE (ALD)

35.  Treatment options include medication, lifestyle changes, and
liver transplants.
 There are still no FDA approved pharmacological or nutritional
therapies for treating patients with ALD.
 Treatment of ALD requires complete cessation of alcohol use.
Also, patients should be encouraged to stop smoking.
 Disulfiram
 Naltrexone
 Acamprosate
 This drugs are approved abstinence and relapse prevention
medications to treat alcohol addiction.
MANAGEMENT OF ALCOHOLIC LIVER
DISEASE (ALD)

36. INFLAMMATORY BOWEL DISEASES (CROHN’S
DISEASE AND ULCERATIVE COLITIS)

37.  There are two forms of idiopathic inflammatory bowel disease
(IBD):
 Ulcerative Colitis
 Crohn's Disease

38.  It is an inflammatory bowel disease (IBD) that causes
inflammation and ulcers (sores) in your digestive tract.
Ulcerative colitis affects the innermost lining of your large
intestine, also called the colon, and rectum. In most people,
symptoms usually develop over time, rather than suddenly.
The Truelove-Witts Classification of UC

39. Montreal classification of severity of ulcerative colitis

40.  Crohn's disease is a type of inflammatory bowel disease (IBD).
It causes swelling of the tissues (inflammation) in your
digestive tract, which can lead to abdominal pain, severe
diarrhea, fatigue, weight loss and malnutrition.
CROHN'S DISEASE
 Inflammation caused by
Crohn's disease can
involve different areas of
the digestive tract in
different people, most
commonly the small
intestine. This
inflammation often
spreads into the deeper
layers of the bowel.

41.  Infectious agents:
 Viruses
 L-Forms of bacteria
 Mycobacteria
 Chlamydia
 Genetics
 Metabolic defects
 Connective tissue Disorder
 Environmental Factors:
 Diet
 Smoking
 Use of NSAID’s
 Oral Contraceptive intake
 Immune Defects
 Altered host susceptibility
 Immune mediated mucosal damage
ETIOPATHOGENESIS OF IBD

42.  Psychological factors:
 Stress
 Emotional or physical trauma
 Occupation

43.  Diarrhea, often with blood or pus
 Rectal bleeding — passing small amount of blood with stool
 Abdominal pain and cramping
 Rectal pain
 Urgency to defecate
 Inability to defecate despite urgency
 Weight loss
 Fatigue
 Fever
 In children, failure to grow
CLINICAL MANIFESTATION OF UC

44.  Diarrhea
 Fever
 Fatigue
 Abdominal pain and cramping
 Blood in your stool
 Mouth sores
 Reduced appetite and weight loss
 Pain or drainage near or around the anus due to inflammation
from a tunnel into the skin (fistula)
 Inflammation of skin, eyes and joints
 Inflammation of the liver or bile ducts
 Kidney stones
 Iron deficiency (anemia)
 Delayed growth or sexual development, in children
CLINICAL MANIFESTATION OF CD

45.  Rehydration
 Supplementation of Nutritional Deficiencies
 Pharmacotherapy
 Supportive care:
 Antidiarrheal Agents
 Anticholinergic Drugs: Relieves Abdominal cramping
 Mild Disease:
 5-aminosalicylic acid Derivatives: Mesalamine, Sulfasalazine,
olsalazine
 Can be administered orally, as suppositories or as enemas
 If no improvement or 5-ASA agents are not tolerated
 Topical Corticosteroids: Budesonide
 Oral systemic Corticosteroids
Pharmacological Management of UC

46. Pharmacological Management of CD
Aminosalicylates: Sulfasalazine, Mesalazine, Olsalazine
Antimicrobials: Ciprofloxacin, Metronidazole
Corticosteroids: Prednisolone, Budesonide
Thiopurines: Azathioprine or Mercaptopurine
Calcineurin Antagonists: Cyclosporine