Drugs For PUD&GERD&Diorrhea by Daniel Chans M July 2022

GIT PHARMACOLOGY
Dept of Pharmacology and

Therapeutics
MUST
danielchans@must.ac.ug
+256772468493
DANIEL CHANS M (MPS)

BPharm, MSc, MPharm
7/26/2022 DANIEL CHANS M MPS 2021 1

OBJECTIVES
By the end of the module, you should be able to;
• Describe the pathophysiology of the different conditions that affect the GIT.
• Describe the pharmacology of drugs used in treatment of GIT disorders (classification

with examples, pharmacokinetics, mechanism of actions, therapeutic uses, adverse effects
and drug interactions)

Discussion Layout
Over view of the different conditions that affect the GIT.
Pathophysiology of the conditions
Causes
Basic pharmacology of the different agents;
• ANTIULCERS
• ANTIDIARRHOEALS
• LAXATIVES
• ANTIEMETICS
• EMETICS
• Ulcerative colitis and IBD

Review of the GIT physiology
Structure of the GIT Functions of the GIT???
• Food passage (peristalsis)
• Temporary food storage
• Food digestion (both physical and
chemical)
• Food absorption
• Water and ion absorption(water and
electrolyte balance)
• Excretion of undigested and previously
digested matter as waste products
• Secretion and control of digestive juices
in various segments of alimentary tract
to ensure controlled digestion and
egestion.
What can go wrong in the GIT?

GIT DISORDERS
 Gastroesophageal Reflux Disease (GERD)
 Peptic Ulcer Disease (PUD)
 Nausea
 Emesis
 IBS
 Diarrhea
 Constipation

Management of GIT disorders
GIT disorder Treatment / class of
dugs
Peptic and duodenal Anti-ulcers drugs
ulcers
Constipation Laxatives / purgatives
Diarrhoea Antidiarrhoeal drugs
Emesis and nausea Anti-emetic agents
Gastro-esophageal Anti-ulcer drugs
reflux disease (GERD)
Inflammatory bowel Anti-inflammatory
disease agents

DISCUSSION
• What are Peptic Ulcers?

• What Factors contribute to Peptic Ulcers?
• What are the aggressive factors?
• What are the protective factors?
• What are the non-pharmacological options?
• What are the Pharmacological Options?

PROBLEM DIRECTED STUDY 1
• A 45-year-old male patient presents with dyspepsia and dull epigastric pain which has been worsening
gradually over the last one month. The pain is partly relieved by food, but becomes worse after 2 hours
or so. Heart burn and pain which awakens him is often felt at night. Epigastric tenderness is detected
on palpation. Upper gastrointestinal endoscopy reveals an ulcer measuring 12 mm X 18 mm in the 1st
part of duodenum. His medical records show that he suffered similar episode of pain about 9 months
ago. No endoscopy was done, but he was treated with omeprazole 20 mg OD for 6 weeks.
Subsequently, nearly 3 months back, he suffered from loose motions and abdominal pain which was
treated with a 5 day course of metronidazole + norfloxacin. Facility for H. pylori testing is not available.
There is no history of NSAID use.
(a) What would be the most appropriate treatment option for him to achieve fast symptom relief, ulcer
healing and prevention of further recurrences?

SOLUTION 1
• WHAT WOULD YOU DO?

PEPTIC AND DUODENAL ULCERS
 Acid and pepsin: Play major pathogenic roles in the development of GIT ulcers and related
conditions.
 Acid-pepsin diseases include peptic ulcers, gastroesophageal reflux and stress -related
mucosal injury.
PEPTIC ULCERS:
 Refers to any ulcer in an area where the mucosa is bathed in the hydrochloric acid and pepsin
(i.e. the stomach and upper part of the duodenum).
 Peptic ulcer disease is chronic, recurs and affects at least 10% of the population in
developed countries. A considerable population suffer from dyspeptic symptoms without
having ulcers (non ulcer dyspepsia).
 Drugs that are effective in the treatment of peptic ulcer either reduce gastric acid secretion
or7/26/2022
increase mucosal resistance to acid-pepsin attacks.
DANIEL CHANS M MPS 2021 11
Peptic Ulcers

STOMACH LINING

GASTRIC MUCOSAL BARRIER
NOTE
•Surface mucosa cells in the pyloric region secrete a thick, alkaline-rich mucus that protects the epithelium of
the stomach and duodenum from harsh acid conditions of the lumen.
•This is known as the gastric mucosal barrier.

•These cells are stimulated by mechanical and chemical irritation and parasympathetic inputs.
•This protective mucus barrier can be damaged by bacterial and viral infection, certain drugs e.g. aspirin.
Gastric Acid Secretion

Peptic Ulcer Disease
PUD linked to
Ca..read
H. pylori is present in
95% of patients with
duodenal ulcers and in Benign PUD
70% of those with
gastric ulcers Malignant PUD:

CAUSES OF PUD
Peptic ulcer disease results when the normal balance of factors that damage or protect the GIT
mucosal barrier is disturbed. Peptic ulcers arise when the;
Aggressive factors
 Increase in acid, pepsin, and bile
 Infection with the bacterium Helicobacter pylori (~ 99% of peptic ulcers)
 Use of nonsteroidal anti-inflammatory drugs (NSAIDs).
Protective Factors:
 Mucus and bicarbonate secretion, prostaglandins, blood flow, and the processes of restitution and
regeneration after cellular injury
N.B
 Almost all patients with gastritis and duodenal ulceration, and 80-90% of patients with gastric
ulcers, are caused by H. pylori infection.
Symptoms of PUD
dyspepsia

Diagnosis? HOW
• Non Invasive Tests
• Urea Breath Test (accurate, specific, active infection and cure detection)
• Stool antigen test for H.Pylori
• Invasive tests
• Serology to test for antibodies (IGG for H.Pylori)
• Endoscopy
• Histology for Biopsy
• Rapid Tissue urease
• Culture and Sensitivity
• PCR
• Fasting Gastrin Test for Zollinger-Ellison Sydrome (read about ZE
syndrome)
ENDOSCOPY

UREA BREATH TEST

Serum Gastrin Level
• Zollinger-Ellison (ZES) syndrome is characterized by gastric acid hypersecretion resulting in
severe acid-related peptic disease and diarrhea (caused by Gastrinomas in duodenum or
pancreas)
• A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison
syndrome. Such cases include the following:
• Patients with multiple ulcers
• Ulcers occurring distal to the duodenal bulb
• Strong family history of peptic ulcer disease
• Peptic ulcer associated with diarrhea, steatorrhea, or weight loss
• Peptic ulcer not associated with H pylori infection or use of nonsteroidal anti-inflammatory
agents
• Peptic ulcer associated with hypercalcemia or renal stones
• Ulcer refractory to medical therapy
• Ulcer recurring after surgery
Gastroesophageal Reflux Disease (GERD)
-Backflow of stomach acid into the esophagus

-Esophagus is not equipped to handle stomach acid => scaring
-Usual symptom is heartburn, an uncomfortable burning sensation behind the
breastbone (MI often mistaken for GERD!)
-More severe symptoms: difficulty swallowing, chest pain
-Reflux into the throat can cause sore throat
-Complications include esophageal erosions, esophageal ulcer and narrowing of the
esophagus
-In some patients (~10%), the normal esophageal lining or epithelium may be
replaced with abnormal (Barrett's) epithelium. This condition (Barrett's esophagus)
has been linked to cancer of the esophagus.
Gastroesophageal Reflux Disease
(GERD)
Endoscope of Barrett’s Esophagus

(can become malignant - needs monitoring)

Symptoms of gastroesophageal reflux disease
Typical Symptoms Acid regurgitation, heartburn
Epigastric fullness, epigastric pressure, epigastric

Atypical Symptoms
pain, dyspepsia, nausea, bloating, belching
Chronic cough, bronchospasm, wheezing,

Extraesophageal Symptoms hoarseness, sore throat, asthma, laryngitis, dental
erosions

Gastroesophageal Reflux Disease
(GERD)
Precipitants:
 Food (fatty food, alcohol, caffeine)

 Night time meals (3h before sleep)
 Smoking
 Obesity
 Pregnancy
Usually chronic relapsing course

Classification of anti-ulcer drugs
A. Agents that reduce intra gastric acidity
• Antacids
• H2-Receptor Antagonists
• Proton Pump Inhibitors
• Prostaglandin analogs
B. Agents that promote mucosal defense

/mucosa; protectants
• Sucrafate
• Chelated bismuth Slideshare.net
• Misoprositol
C. Antimicrobials
• Metronidazole
• Amoxicillin
• Clarithromycin
• Tetracycline
• 7/26/2022
Bismuth subsalicylate DANIEL CHANS M MPS 2021 27
Drugs used in PUD…
doctorlib.info
Classification of drugs used in peptic ulcer
1. Drugs that inhibit gastric acid secretion
a. Proton-pump inhibitors (PPIs): Omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole, dexlansoprazole
b. H2-receptor antagonists (H2-blockers): Cimetidine, ranitidine, famotidine, roxatidine.
c. Antimuscarinic agents (Anticholinergic agents): Pirenzepine, telenzepine.
d. Prostaglandin analogues: Misoprostol.
2. Ulcer protective : Sucralfate, colloidal bismuth subcitrate (CBS).
3. Drugs that neutralize gastric acid (antacids)
• a. Systemic antacids: Sodium bicarbonate, sodium citrate.
• b. Non-systemic antacids: Magnesium hydroxide, magnesium trisilicate, aluminum
hydroxide, calcium carbonate.
4. Anti-Microbials
• Amoxicillin, tetracycline, clarithromycin, metronidazole, tinidazole, bismuth
subsalicylate, Nitazoxanide, Rifabutin, …
PROTON PUMP INHIBITORS
• Strong inhibitors of gastric acid secretion through irreversible inhibition of proton pump, preventing “pumping”
or release of gastric acid (24 hr action)
• Indicated in PUD, Gastritis, GERD, & Zollinger-Ellison syndrome
• Faster relief and healing than H2 receptor blockers
• Decreases acid secretion by up to 95% for up to 48 hours
• 2, or 4-8 week course of treatment (maybe longer)
Omeprazole Lansoprazole
Rebeprazole
Esomeprazole
Pantoprazole
PROTON PUMP INHIBITORS
Prototype: Omeprazole
 Others: Lansoprazole , rabeprazole , pantoprazole , and esomeprazole etc.
MOA: The drug is converted into sulfenamide which combines covalently with a cysteine
residue of the H+/K+-ATPase (proton pump), forming a stable covalent bond.
This results into inhibition of the H+/K+-ATPase proton pump that controls H+ secretion
from parietal cells into secretory canaliculi
Therapeutic uses:
 PUD
 GERD
N.B They Reduce the risk of bleeding from an ulcer caused by aspirin and other NSAIDs
 They are also successfully used with antimicrobial regimens to eradicate H. pylori.
Pharmacokinetics:
 Some of these agents are delayed-release formulations and are effective orally and some are also available
for intravenous injection.
 Have a long duration of action.
 Metabolites of these agents are excreted in urine and faeces.
Adverse effects and drug interactions:
• There are increased reports of diarrhoea and Clostridium difficile colitis in community patients receiving
PPIs; therefore, patients must be counselled to discontinue PPI therapy if they have diarrhoea for several
days and to contact their physicians for further follow-up.
 Omeprazole inhibits the metabolism of warfarin, phenytoin, diazepam, and cyclosporine. However, drug
interactions are not a problem with the other PPIs.
 Prolonged therapy, may result in low vitamin B12, because acid is required for its absorption.
 What are other SEs of Omeprazole ….Long term use ???

N.B:
 For maximum effect, PPIs should be taken 30-60 minutes before meals e.g. breakfast
or the largest meal of the day. (except dexlansoprazole)
 Their long duration of action is due to their irreversible inhibition of H+/K+ ATPase
pump.
 Sulfenamide, unlike omeprazole doesn’t readily cross cell membrane, and therefore it
accumulates in the canaliculi of parietal cell, thus PPIs have little action on other
pumps in the body.
 Prolonged Use may increase risk of GI cancer?

• Adverse Effects
• Adverse reactions to omeprazole include headache, diarrhea, abdominal pain, nausea, dizziness, vomiting, and
constipation. Long term use: Pneomonea, C.defficile infection, Vit B12 deficiency, Osteoporosis, Dementia,
Increased Ca risk, Hypergastrineamia,
• Not recommended for long-term use in patients with gastroesophageal reflux disease, duodenal ulcers, and in
lactating women.
• Adverse effects of lansoprazole are fatigue, dizziness, headache, nausea, diarrhea, constipation, anorexia, or
increased appetite.
• Contraindications and Precautions
• Proton pump inhibitors are contraindicated in long-term use for gastroesophageal reflux disease (GERD) and
duodenal ulcers.
• They are also contraindicated in patients with hypersensitivity to these agents and children younger than two
years, and during pregnancy (categories B and C).
• Lansoprazole should be avoided in patients with severe hepatic impairment.
• Proton pump inhibitors are used with caution in patients with dysphasia, metabolic or respiratory alkalosis,
and hepatic disease, and during pregnancy.
• Drug Interactions
• Omeprazole increases serum levels and potentially increases the
toxicity of benzodiazepines, phenytoin, and warfarin.
• This agent shows decreased absorption with sucralfate (these
drugs should be given at least 30 minutes apart).
• Lansoprazole decreases serum levels if taken concurrently with
sucralfate.
• It decreases serum levels of ketoconazole and theophylline.
• Proton pump inhibitors decrease the bioavailability of itraconazole,
iron salts and other drugs that require gastric PH for absorption.
• Inhibits CYP2C19…could inhibit activation of prodrug clopidogrel,
reducing its antiplatelet effects and lead to increased cardiovascular
events.
Histamine H2 Receptor Blockers
• Inhibit secretion of gastric acid through competitive inhibition of Histamine H2 receptors
• Prevention & tx of PUD, Esophagitis, GI bleeding, stress ulcers, and Zollinger-Ellison Syndrome
• May alter the effects of other drugs through interactions with CYP450 (especially cimetidine)
• Suppresses 24 hour gastric secretion by 70%
• Good for night symptoms in GERD
• The development of tachyphylaxis within two to six weeks of initiation of H2RAs limits
their use in the management of GERD
7/26/2022 Cimetidine FamotidineDANIEL CHANS

Ranitidine
M MPS 2021 Nizatidine 36
H2 -RECEPTOR ANTAGONISTS
Examples of H2 antagonists
 1st generation: Cimetidine
 2nd generation: Rinatidine, Nizatidine and Famotidine
Suppression of acid release is less than with PPIs because only the histamine component is
inhibited.
Adding H2-receptor antagonists (H2RAs) at bedtime to high-dose proton pump inhibitors is likely to enhance nocturnal gastric pH control
and decrease nocturnal gastric acid breakthrough.
MOA
H2 receptor blockers competitively block histamine induced acid release by parietal cells.
NB. Cimetidine has a weak antiandrogen, and may cause gynaecomastia and sexual dysfunction in
males.
In the elderly particularly it may cause CNS disturbances like lethargy, hallucinations and confusion.
It inhibits CYP450 enzymes, hence it increases a potential risk of adverse effects for drugs like
Warfarin, Phenytoin, Lidocaine and Propranolol which are inactivated by this enzyme.

2nd Generation H2 receptor antagonists
Differences from cimetidine lie chiefly in dose and in profile of unwanted side effects.
PK
 Administered orally and Ranitidine have a t 1/2 2h, famotidine - t 1/2 3h and nizatidine - t 1/2
1h. Incompletely metabolised in the liver, and metabolites and the unchanged drug is
excreted in the kidney.
Adverse effects
 CNS: Headache, dizziness, and reversible confusion,
 GIT: Constipation and diarrhoea may occur.
 Urticaria, sweating and somnolence are reported with nizatidine.
N.B: The drugs do not inhibit hepatic microsomal enzymes and do not block androgen
receptors hence the absence of some adverse effects seen in 1st Generation drugs.
Anticholinergics
Pirenzipine
• Muscarinic M1 acetylcholine receptor antagonist
• Blocks gastric acid secretions
• About as effective as H2 blockers
• Rarely used clinically
• Anticholinergic side effects (anorexia, blurry vision, constipation, dry mouth,

sedation)

Antacids
Systemic Antacid: Sodium Bicarbonate
Non-systemic Antacid:
Aluminum Hydroxide + Magnesium Hydroxide Combinations (Maalox and Mylanta)
Contraindicated in patients with impaired renal function
Magnesium may cause diarrhea
Aluminium may cause constipation
Calcium Carbonate (Tums)

Calcium may cause constipation

Antacids
Antacids have a number of actions which include;
• Neutralizing gastric acid and thus relieving associated pain and

nausea
• Reducing delivery of acid into the duodenum following a meal
• Inactivation of the proteolytic enzyme pepsin by raising the gastric

pH above 4–5

Prostaglandins- Misoprostol
• PGE1 analog
• Stimulates Gi pathway, leading to decrease in gastric acid release
• For treatment of NSAID induced ulcers
• Side effects include diarrhea, pain, and cramps (30%), abortion
• Contraindicate in pregnancy because it can cause birth defects, and

premature birth
7/26/2022 DANIEL CHANS M MPS 2021 Misoprostol 43

USES
These include the following:
Healing of duodenal ulcer and gastric ulcer, including those induced by NSAIDs
Prophylaxis of gastric and duodenal ulceration in patients on NSAID therapy
Adverse effects
• Diarrhoea, abdominal pain, nausea and vomiting, dyspepsia, flatulence, abnormal
vaginal bleeding, rashes and dizziness may occur.
• The most frequent adverse effects are gastrointestinal and these are usually dose
dependent.
Contraindications
• Pregnancy (or desired pregnancy) is an absolute contraindication to the use of
misoprostol, as the latter causes abortion.

Summary of Acid Reduction therapeutics
Antacids
H+ Cl-

Sucralfate (carafate) MUCOSAL PROTECTIVE AGENTS
• Can be used to prevent & treat PUD
• It requires an acid PH to activate
• Forms sticky polymer in acidic environment and adheres to the ulcer site, forming a
barrier
• May bind with other drugs and interfere with absorption
• Give approximately 2 hours before or after other drugs
• Take on an empty stomach before meals

Chelated Bismuth
• Protects the ulcer crater and allows healing
• Some activity against H. pylori
• Should not be used repeatedly or for more than 2 months at a
time
47
• Can cause black stools, constipation
HELICOBACTER PYLORI
• H. pylori are bacteria able to attach to the epithelial cells of the stomach and
duodenum which stops them from being washed out of the stomach.
• Once attached, the bacteria start to cause damage to the cells by secreting
degradative enzymes, toxins and initiating a self-destructive immune response.
ANTIMICROBIALS
 H. pylori is implicated in the production of gastric and, more particularly, duodenal
ulcers and is a risk factor for gastric cancer.
 To reduce the incidence of recurrence of peptic ulcer associated with H pylori
infection, treatment regimens must include eradication of H. pylori.
 Combination therapy; Tripple therapy (i.e. three drugs from different classes), is
employed to eradicate H. pylori infection. The triple therapy should include: 1PPI and
2 antibiotics.
 Quadruple therapy eg with Bismuth cpd is avialable
 Omeprazole and metronidazole or amoxicillin plus clarithromycin is often
recommended.
 The therapy is given twice daily for 14 days and the choice of metronidazole or
amoxicillin depends on the local pattern of H. pylori resistance.
 In resistance cases, however, a PPI has also been used as part of ‘quadruple
therapy’ with amoxicillin and clarithromycin plus
DANIEL CHANS M metronidazole.
MPS 2021 49
Anti-H.pylori Therapy (antimicrobials)
• Antibiotic Ulcer Therapy - Used in Combinations H. pylori is present in
95% of patients with
• Clarithromycin - Inhibits protein systhesis duodenal ulcers and in
70% of those with
• Amoxicillin - Disrupts cell wall gastric ulcers
• Tetracycline - Inhibits protein synthesis
• Metronidazone (nitroimidazole) - Used often
due to bacterial resistance to amoxicillin and
tetracycline, or due to intolerance
• Others..eg…Tinidazole, Nitazoxanide
Triple Therapy Proton pump inhibitor + amoxicillin/tetracycline +
metronidazone/clarithomycin
Quadruple Therapy –
-Add Bismuth Quadruple Therapy (Bismuth and 2 antibiotics-
Tetracycline+Nitroimidazole or ) plus a PPI e.g B,T,M pill QID and Omez BD for 10-14
days
N.B Resistance and reactions by alcoholics to metronidazole limits its use 50
Some kits on the market
Low dose of clarithro

ACG 2017 Guidelines for HPI (Medscape.com)
• First-line treatment
• 10-14 days of bismuth quadruple therapy (bismuth, proton pump inhibitor [PPI], tetracycline, and a
nitroimidazole), particularly in those with previous macrolide exposure or are penicillin allergic
• 10-14 days of concomitant PPI, clarithromycin, amoxicillin, and a nitroimidazole
• 14 days of clarithromycin triple therapy (clarithromycin, a PPI, and amoxicillin or metronidazole)

should be reserved for patients with no previous history of macrolide exposure who live in regions
where clarithromycin resistance among H pylori isolates is known to be low (< 15%)
• 5-7 days of sequential therapy with a PPI and amoxicillin, followed by 5-7 days with clarithromycin,
a PPI, and a nitroimidazole
• 7 days of a hybrid therapy with a PPI and amoxicillin, followed by 7 days with a PPI, amoxicillin,
clarithromycin, and a nitroimidazole (conditional recommendation)
• 10-14 days of levofloxacin triple therapy (levofloxacin, a PPI, and amoxicillin)
• 5-7 days of fluoroquinolone sequential therapy (a PPI and amoxicillin), followed by 5-7 days of a
PPI, fluoroquinolone, and nitroimidazole

Salvage treatment if first-line therapy fails and HPI persists
include the following options
• Pts previously on clarithromycin therapy should receive Bismuth

Quadruple therapy (BQT) or Levofloxacin Salvage regimens
• Pts previously on BQT shd receive Clarithromycin or Levofloxacin salvage
regimens
• Salvage treatment regimens
• BQT or Levofloxacin tripple therapy for 14 days
• Concomitant therapy for 10-14 days (avoid Clarithro Tripple therapy)
• Rifabutin Tripple therapy for 10 days (Rifabutin+PPI+Amoxicllin)
• High dose Dual Therapy for 14 days (PPI+Amoxicillin)

ASSIGNMENT
• Please look up the individual doses of the above drugs
• MOAs for the Antibiotics (to be covered fully under Chemotherapy)
• Advances in Treatment of H.P.I
• Nitazoxanide therapies
• UCG guidelines for H.P.I eradication

https://www.semanticscholar.org/paper/ACG-Clinical-Guideline%3A-Treatment-of-Helicobacter-
Chey-Leontiadis/da1ba270c1f57350ae5004df20a021fff9166e94

UCG,2016 GUIDELINES

Non-Pharmacological Options

Considerations in Treatment of peptic ulcer
• Endoscopy is definitive diagnostic test for ulcers
• Antimicrobial agents to eradicate H. pylori infection
• Misoprostol (a prostaglandin analog) to inhibit gastric acid secretion and increase carbonate and mucus
production, to protect the stomach lining: pregnancy CI
• Antacids to neutralize acid gastric contents by elevating the gastric pH, thus protecting the mucosa and relieving
pain
• Avoidance of caffeine and alcohol to avoid stimulation of gastric acid secretion
• Test for cure/H.pylori eradication 4 weeks after completion of AbX therapy AND 1-2 wks withholding PPIs
• H2 blockers to reduce acid secretion
• Sucralfate, mucosal protectant to form an acid-impermeable membrane that adheres to the mucous membrane
and also accelerates mucus production
• Dietary therapy with small infrequent meals and avoidance of eating before bedtime to neutralize gastric
contents
• Gastroscopy to allow visualization of the bleeding site and coagulation by laser or cautery to control bleeding
• Surgery to repair perforation or treat unresponsiveness to conservative treatment, and suspected malignancy.

What is the Non-Pharmacological plan for PUD/GERD?
• How about NSAID Induced Ulcers

Quizlet.com
7/26/2022 60
MUST READ: HOW EXACTLY IS GERD
MANAGED?..NOW…

ANTIDIARRHOEAL AGENTS

PROBLEM DIRECTED STUDY 2
• A 35-year-old man has come with complaint of acute onset diarrhoea.
The stools are relatively small volume, liquid but not watery, frothy and are
preceded by griping pain in abdomen. Foul smelling wind, eructation and mild
fever are the other complaints. He has passed 4 loose motions in the past 8
hours and there is no appetite. He admits to have eaten spicy snacks last
evening at a road side stall. Physical examination reveals body temperature
101°F, no signs of dehydration, but diffuse abdominal tenderness. A tentative
diagnosis of enteroinvasive diarrhoea is made.
(a) Does this patient require rehydration therapy?
(b) Should an antibiotic be prescribed? If so, which antibiotic would be
appropriate?
(c) Should an antimotility-antidiarrhoeal drug be coprescribed to reduce the
number of stools?
(d) Should any other symptomatic drug be given to him?
(e) Describe Pharmacology of drugs used in Diarrhea
SOLUTION 2

Antidiarrhoeal agents
• Diarrhea is the frequent passage of watery, unformed stools (>3 motions in 24
hours)
• Diarrhea ranges from mild and socially inconvenient illness to a major cause of
death among children in less developed countries.
• Drugs have a place in management but the first priority of therapy is to preserve
fluid and electrolyte balance.
Causes of diarrhea
• Increased Secretion into the GIT due to toxins
• Increase in the motility of the GIT
• Infections with enteric organisms, inflammatory bowel disease, thyrotoxicosis,
nutrient malabsorption.
• Medication side effect (e.g. quinolone and aminoglycosides),and laxative abuse,
cholinergic drugs.
• Poisoning DANIEL CHANS M MPS 2021 66
• What causes diarrhoea?
• There are many different causes of diarrhoea, but a bowel infection (gastroenteritis) is a common
cause in both adults and children.
• Gastroenteritis can be caused by:
• a virus – such as norovirus or rotavirus
• bacteria – such as campylobacter and Escherichia coli (E. coli), which are often picked up from
contaminated food
• a parasite – such as the parasite that causes giardiasis, which is spread in contaminated water
• These infections can sometimes be caught during travel abroad, particularly to areas with poor
standards of public hygiene. This is known as travellers' diarrhoea.
• Anxiety, a food allergy, medication, or a long-term condition, such as irritable bowel syndrome (IBS).
• Other: Shigella, Salmonella Typhii, Vibrio, C.Defficle
• Drugs eg……

Management of diarrhoea
The three approaches used in the treatment of severe acute

diarrhoea:
• Maintenance of fluid and electrolyte balance
• Use of antimotility drugs and adsorbents
• Use of anti-infective agents

MAINTENANCE OF FLUID AND ELECTROLYTE BALANCE
TREATMENT
• Oral rehydration therapy (ORT) with glucose electrolyte solution is sufficient to
treat the varsity majority of episodes of watery diarrhoea from acute
gastroenteritis.
• ORT is effective because glucose coupled sodium transport continues during
diarrhoea and so enhances the replacement of water and electrolyte losses in the
stool.
• It’s the mainstay treatment for viral origin diarrhoea, except in severe electrolyte
loss that is when I.V therapy is needed.
• Many patients require no other treatment especially children whose diarrhoea is
of viral origin.
NB. Glucose stimulates the absorption of sodium and the resulting water flow also
sweeps additional sodium and chloride along with it (solvent drug).
Water absorption by glucose is the basis of oral rehydration regimens.
Oral and parenteral rehydration.
• In acute diarrhea, death is usually due to dehydration rather than the specific infective
organism.
• it is important to maintain water and electrolyte balance with proper fluid replacement.
• Oral rehydration seems to be the simplest, safest, least expensive and lifesaving method of
choice for acute diarrhea.
• WHO–ORS contains sodium chloride 2.6 g, potassium chloride 1.5 g, sodium citrate 2.9
g and glucose 13.5 g. It has to be dissolved in 1 L of water.
• This provides sodium 75 mM, potassium 20 mM, chloride 65 mM, citrate 10 mM and
glucose 75 mM.
• In case of severe diarrhea with dehydration, intravenous fluids are indicated.,,e.g???
• Super ORS, an improved form of ORS with substitution of glucose with boiled rice powder,
helps in rehydration and also decreases the frequency of diarrhea.
Antimotility drugs
These act on the bowel muscle to delay the passage of gut contents so allowing time
for more water to be absorbed.
The agents are classified into:
• Muscarinic receptor antagonists: Atropine
• Opiates: codeine, diphenoxylate and Loperamide
Muscarinic receptor antagonists
• These agents are seldomly employed as primary therapy for diarrhoea because of
their actions on other systems.
• Small doses of Atropine is often prepared in combination with diphenoxylate in
treatment of diarrhoea.

Opioids
• They activate opioid receptors on smooth muscles of the bowel to diminish
propulsive activity and increase segmentation contractions.
• The faeces become dehydrated as a result of their longer stay in the GI tract.
• Mechanism of action of opoids
• Decreases fluid secretion;
• Increases fluid absorption;
• Decreases propulsive contractions;
• Increases segmenting contractions;
• Delays gastric emptying.

• Loperamide has a relatively selective action on the gastrointestinal tract and undergoes
extensive hepatic metabolism.
• In traveller's diarrhoea, loperamide reduces the frequency of passage of faeces and the
duration of the illness.
• Diphenoxylate is given once in the therapeutic dose suitable for diarrhoea, does not
have morphine-like activity in the CNS, though large doses produce typical opioid
effects. Preparations of diphenoxylate usually contain atropine as well.
Contraindication
• Loperamide is not recommended for use in children younger than 2 years of age.
• Opoids are contraindicated in infections caused by enteroinvasive bacteria such as
shigella; because they delay clearance of the organism, prolonging the diarrhoea and
accompanying fever.
Side effects of opioids
Constipation, abdominal cramps, drowsiness, dizziness, paralytic ileus
Some Opioid Drugs Act Both in the CNS and on Enteric Nerves,
Others Act Only on Enteric Nerves
Drug Central Nervous Enteric Nerves

System
Morphine +++ +++
Codeine +++ +++
Diphenoxylate + +++
Loperamide 0 +++
Loperamide does not effectively cross the blood-brain barrier

7/26/2022 after oral administration and exerts mainly
DANIEL CHANS peripheral effects
M MPS 2021 75
Others- Bismuth subsalicylate
• Used for traveller's diarrhoea and is said to be safe in healthy young adults and is reported to prevent
up to 65% of cases of diarrhoea in areas of high risk.
• It decreases fluid secretion in the bowel and may work largely by virtue of its salicylate component.
• Bismuth subsalicylate can cause tinnitus and blackening of the faeces.
• Caution should be exercised with regard to the total dose given to patients taking salicylates for other
reasons to avoid salicylism
Co-phenotrope
• This is a combination of atropine and diphenoxylate.
• It can produce a typical antimuscarinic of blurred vision and dry mouth and there is little evidence
to suggest that the combination has advantages.

Adsorbents
E.g. Kaolin & pectin, activated-charcoal
• Kaolin is a naturally occurring hydrated magnesium aluminum silicate, and

pectin is an indigestible carbohydrate derived from apples.
• Both appear to act as adsorbents of bacteria, toxins, and fluid, thereby

decreasing stool liquidity.
• They may be useful in acute diarrhea but are seldom used on a chronic basis.
• A common commercial preparation is Kaopectate.
• Kaolin-pectin formulations are not absorbed and have no significant adverse

effects except constipation. They should not be taken within 2 hours of other
medications which they may bind.

Use of anti-infective agents
• The use of anti-infective agents is usually not necessary in simple gastroenteritis
since most infections are usually viral in origin, and those that are bacterial generally
resolve without antibacterial drug therapy.
Rotavirus…..
• Most cases of traveller’s diarrhoea are caused by Escherichia coli, Shigella and
Salmonella spp, Viruses including Norwalk family, and parasite (particularly Giardia
lambria).
• This type of diarrhoea usually lasts for 3-4 days, this may be a social inconvenience
and severe infections (e.g. typhoid, amoebic dysentery and cholera) may require
erythromycin or ciprofloxacin (500mg B.D) or other antibiotics (metronidazole,
nitazoxanide etc depending on the cause. Rifaximin can also treat traveler’s diarrhea
effectively.
NB:
The use of antibiotics that destroy the normal flora, as well as the pathogen, may allow
growth of organisms such as Clostridium difficile, which can cause serious
pseudomembranous colitis requiring treatment with either metronidazole or vancomycin

How do u treat depending on the cause? Which
Antibiotic
• Shigella?
• Salmonella?
• E.coli?
• Campylobacter?
• Girdiasis?
• C.defficile?

Clostridium Difficile
•The major cause of diarrhea and colitis in patients exposed to antibiotics (~20%).
•Fecal - oral route of transmission
•Three steps to infection
•Alteration of normal fecal flora
•Colonic colonization of C. difficile
•Growth and production of toxins
•Infection can lead to formation of colitis and toxic megacolon
•Pharmacological Treatment
• Discontinue offending antibiotic
• Metronidazole
•Vancomycin
Probiotics
• Probiotics are dietary supplements containing bacteria (Lactobacillus species,
Bifidobacterium species, and others) that may promote health by enhancing the
normal microflora of the GI tract while resisting colonization by potential pathogens.
• Probiotics can stimulate the immune response and suppress the inflammatory
response.
• Probiotics can be taken in tablets, gummies, capsules, powders, and liquids.
• Yogurt may provide relief from diarrhea due to lactose intolerance.
• The Lactobacillus acidophilus in yogurt, cottage cheese, and acidophilus milk
improve digestion of lactose and may prevent or relieve diarrhea related to lactose
deficiency and milk intake.
• lactase is not a probiotic but lactase tablets may also be used to prevent
diarrhea in susceptible patients.
Non-pharmacological plan
• WHAT ARE THE NON-PHARMACOLOGICAL METHODS
• WHAT IS THE ROLE OF ZINC?
• OTHER TREATMENT MODALITIES

UCG 2016 Guidelines

• END

Drugs For PUD&GERD&Diorrhea by Daniel Chans M July 2022

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Drugs For PUD&GERD&Diorrhea by Daniel Chans M July 2022

Uploaded by

Copyright:

Available Formats

GIT PHARMACOLOGY

Dept of Pharmacology and

DANIEL CHANS M (MPS)

7/26/2022 DANIEL CHANS M MPS 2021 1

• Describe the pharmacology of drugs used in treatment of GIT disorders (classification

7/26/2022 DANIEL CHANS M MPS 2021 2

7/26/2022 DANIEL CHANS M MPS 2021 3

7/26/2022 DANIEL CHANS M MPS 2021 5

 Peptic Ulcer Disease (PUD)

7/26/2022 DANIEL CHANS M MPS 2021 6

7/26/2022 DANIEL CHANS M MPS 2021 7

• What are Peptic Ulcers?

7/26/2022 DANIEL CHANS M MPS 2021 8

7/26/2022 DANIEL CHANS M MPS 2021 9

7/26/2022 DANIEL CHANS M MPS 2021 10

7/26/2022 DANIEL CHANS M MPS 2021 12

7/26/2022 DANIEL CHANS M MPS 2021 13

•This is known as the gastric mucosal barrier.

7/26/2022 DANIEL CHANS M MPS 2021 15

7/26/2022 DANIEL CHANS M MPS 2021 16

7/26/2022 DANIEL CHANS M MPS 2021 18

7/26/2022 DANIEL CHANS M MPS 2021 20

7/26/2022 DANIEL CHANS M MPS 2021 21

-Backflow of stomach acid into the esophagus

Endoscope of Barrett’s Esophagus

7/26/2022 DANIEL CHANS M MPS 2021 24

Typical Symptoms Acid regurgitation, heartburn

Epigastric fullness, epigastric pressure, epigastric

Chronic cough, bronchospasm, wheezing,

7/26/2022 DANIEL CHANS M MPS 2021 25

 Food (fatty food, alcohol, caffeine)

Usually chronic relapsing course

7/26/2022 DANIEL CHANS M MPS 2021 26

B. Agents that promote mucosal defense

 Have a long duration of action.

 Metabolites of these agents are excreted in urine and faeces.

Adverse effects and drug interactions:

 What are other SEs of Omeprazole ….Long term use ???

 Prolonged Use may increase risk of GI cancer?

7/26/2022 DANIEL CHANS M MPS 2021 33

• Contraindications and Precautions

• Lansoprazole should be avoided in patients with severe hepatic impairment.

7/26/2022 Cimetidine FamotidineDANIEL CHANS

7/26/2022 DANIEL CHANS M MPS 2021 37

• Muscarinic M1 acetylcholine receptor antagonist

• Blocks gastric acid secretions

• About as effective as H2 blockers

• Rarely used clinically

• Anticholinergic side effects (anorexia, blurry vision, constipation, dry mouth,

7/26/2022 DANIEL CHANS M MPS 2021 39

Calcium Carbonate (Tums)

7/26/2022 DANIEL CHANS M MPS 2021 40

• Neutralizing gastric acid and thus relieving associated pain and

• Reducing delivery of acid into the duodenum following a meal

• Inactivation of the proteolytic enzyme pepsin by raising the gastric

7/26/2022 DANIEL CHANS M MPS 2021 41

• Stimulates Gi pathway, leading to decrease in gastric acid release

• For treatment of NSAID induced ulcers

• Side effects include diarrhea, pain, and cramps (30%), abortion

• Contraindicate in pregnancy because it can cause birth defects, and

7/26/2022 DANIEL CHANS M MPS 2021 Misoprostol 43

7/26/2022 DANIEL CHANS M MPS 2021 44

7/26/2022 DANIEL CHANS M MPS 2021 46