Transcript PEPTIC ULCER DISEASE

 Peptic
ulcers are the areas of degeneration
and Necrosis of gastrointestinal mucosa
exposed to acid-peptic secretions.
 The
term peptic ulcer describes a condition
in which there is a discontinuity in the entire
thickness of the gastric or duodenal mucosa
that persists in the gastric juice.
 Peptic
ulcer is usually represented as
Dyspepsia.
 Acute
or stress ulcers : Multiple, Small
mucosal erosions.
 Chronic
ulcers: Gastric or Duodenal ulcers.
 Occurs
due to imbalance between the
aggressive and defensive factors.
 Etiological factors of Acute ulcers :
A. Psychological stress
B. Physiological stress




Shock
Severe trauma
Drugs and Local irritants
Cushing’s syndrome
 Chronic
ulcer disease : Multifactoral, the main
contributing factor is the H-Pylori infection.

Acid-pepsin secretions

Mucus secretion

Gastritis
 Local Irritants
 Dietary factors
 Psychological factors
 Genetic factors
 Hormonal factors
 Miscellaneous factors
 Viral
Infections (cytomegalovirus)
 Radiation
 Chemotherapy
( e.g. hepatic artery
infusions)
 Idioathic
 Vascular
insufficiency
 Cigarette
smoking
Infection
Few months
Years
Mucosal
layer erosion
• H-Pylori Infection
• Chronic superficial gastritis
• Hyperacidity
• Peptic ulcer
 H-Pylori
contains enzymes like urease,
protease, catalase, phospholipase which
damage the mucosal barrier.


Basal and Maximal acid output due to
various stimuli.
Vagal stimulation
 Gastric
Ulcer : Impaired gastric mucosal
defenses against acid-pepsin secretions.
 Pathogenesis :
serum gastrin levels due
to ingested food leading to hyperacidity.



Acid secretion because of
mass.
parietal cell
Inhibition of gastric acid secretion.
Hco3- secretion in the duodenum due to HPylori infection
causing local release of
cytokins and further damage.
 NSAIDS
induced peptic ulcer :
NSAIDS
COX
inhibition
Adherence
of
leucocytes
to mucosal
endothelial
cells
Decreased
prostaglan
din
synthesis
Superficial
erosions
Peptic
ulcer
A
number of other factors may contribute to
the development of NSAID induced mucosal
injury, neurtophils adherence may damage
vascular endothelium and cause reduced
mucosal blood flow or may release oxygen
derived free radicals and proteases.
 Leukotriens
have stimulatory effect on
neutrophils adherence.
 Topical
irritant properties associated with the
acidic properties of NSAID’s e.g. aspirin and
their ability to decrease hydrophobicity of
mucosal gel layer
 Epigastric
pain
 Upper
abdominal pain occurring 1-3 Hrs after
meals and relieved by food or antacids is a
classical symptom of peptic ulcer disease.
 Anorexia, weight loss.
A
typical nocturnal pain that awakens the
patient from sleep.
 Heart
burn due to acid regurgitation.
 Nausea
may accompany the pain.
 Diagnosis
of H-Pylori infection .

Non-Invasive techniques:
A.
C.
Urea breath test
Serological tests
Stool test
•
Invasive techniques
A.
Rapid urease test
Culture
Histology
B.
B.
C.
 13C
Urea breath test : used to demonstrate
eradication of organism following
treatment.
Serological test : used to detect antibodies
 Used in diagnosis and epidemiological studies.

Stool test : Immunoassay using monoclonal
antibodies for qualitative detection of H-Pylori that
leads to colour change that can be detected visually
or by spectrophotometer.
 Used in the diagnosis and monitoring efficacy of
eradication therapy.

Culture : Biopsies cultured on a special medium
 Enables sensitivity testing to determine optimum
treatment or antibiotic resistance.


Histology : Gastric mucosal staining, helps in the
classification of gastritis.tests for active HP infection.
 Biopsies
are done to exclude malignancy and
uncommon lesions such as crohn’s disease.
 Wireless
capsule endoscopy : determines
NSAIDS induced ulceration of small intestine.
 Use
of gastrograffin meal:
 Gastrografin (Diatrizoate Meglumine and
Diatrizoate Sodium Solution) is a iodinated
radiopaque contrast medium for oral or rectal
administration only.
 Rapid
urease test :
Gastric biopsies
with urea solution
containing phenol
Urea ammonia
PH
Rapid colour
change
 Esophagogastroduodenoscpy
: permits
direct visualization of superficial erosions
and sites of active bleeding.
 Routine
single barium contrast
techniques :
 Fasting
serum concentration studies :
 Non
pharmacological therapy :
I. Reduce psychological stress
II. Reduce physical stress
III. Cessation of cigarette smoking
IV. Stop use of NSAIDS
V. Avoid spicy foods, caffeine, alcohol
VI. Drink plenty of water
VII. Avoid fasting and maintain optimum gap
between meals
 Classification
1.
2.
3.
4.
5.
6.

of Drugs:
Proton Pump Inhibitors : e.g. omeprazole,
pantaprazole,Lansoprazole.
H2receptor antagonists : e.g. Ranitidine,
Famotidine, cimetidine
Sucralfate
Bismuth compounds
Antacids : systemic e.g. Sodium bicarbonate,
Non Systemic e.g. Magnesium Trisilicate.
Prostaglandin Analogs : e.g. misoprostol,
Enprostil.
Anti H-Pylori drugs (Antibiotics) e.g.
Amoxicillin, clarythromycin, tetracyclines.
Proton Pump
Inhibitors
Inhibit acid
secretion
Carried in
blood stream
to the parietal
cells
Inhibition of H+
K+ ATPase
Activation
Cytosol
ESC




PPI’s differ in their in their potencies.
Plasma concentration is reached after 2-3 hrs.
T1/2 48 Hrs.
To be taken 30 minutes prior to food.
2. H2receptor antagonists :

Structural analogs of histamine.

pepsinogen ( )
pepsin

Used in symptomatic treatment.

Plasma concentration is reached within 1-3Hrs
after administration.

Recommended in patients with nocturnal gastric
acid secretion and
management of dyspepsia
symptoms.
 Sucralfate
sucrose
: Basic aluminium salt of sulfated
Polymerizes at pH
< 4.0 by cross
linking of
molecules
Gel
Adheres to the
ulcer base
Antacids are contraindicated when sulfates are
taken
Precipitates surface
proteins and acts as
a physical barrier
 Prostaglandin
Analogs :cytoprotective
properties
1. Increase mucus and bicarbonate
production.
2. Increase mucosal blood flow
3. Inhibit gastrin production

Mgsio3
Antacids : ANC--- No of Meq of 1N Hcl that
are brought to pH 3.5
in 15 minutes by unit
Cl salt
dose of antacid preparation.
-
Cl- + HCo3-
No acid-base
disturbance

Decision algorithm for management of uninvestigated
Dyspepsia
 BLEEDING
PEPTIC ULCER :
 Patients with high risk of bleeding are given
high dose of infusion of omeprazole ( 80 mg
bolus followed by 8mg/Hr) for 72 Hrs to
reduce rebleeding.
 LATE
COMPLICATIONS OF PEPTIC
ULCER:
 Reactive hypoglycaemia, diarrhoea, weight
loss, anaemia, flushing, plapitation, sweating
tachycardia, postural hypotension.
 Treatment
:
 Somatostatin analogs for reactive
hypoglycaemia.
 Antibiotics
 metachlopramide
 Zollinger-ellison
syndrome: use of
octreotide, surgical.
 Assess
 Assess
patient allergies
patient use of alcohol or alcoholcontaining products with metronidazole and
oral birth control medications with antibiotics
and counsel appropriately.
 Inform the patient of change in stool color when
bismuth salicylate is included in an HP
eradication regimen.
 Assess and monitor patients for potential
adverse effects.
 Assess and monitor patients for potential drug
interactions.
 Monitor patients for salicylate toxicity.
o Provide education to patients who are receiving HP
eradication therapy, including why antibiotic and
antiulcer combinations are used, when and how to take
medications, adverse effects, alarm symptoms, when to
contact their health care provider, and the importance of
compliance to drug
treatment.
NSAID-induced ulcer
Recommend drug treatment
Assess risk factors for NSAID-induced ulcers and
ulcer-related
complications, and when indicated recommend
appropriate
strategies for reducing ulcer risk.
Assess and monitor patients for potential drug
 Misoprostol, 200
mcg four times a day,
markedly reduces the risk of NSAID-induced
gastric ulcer, duodenal ulcer, and ulcer-related
GI complications, but diarrhea and abdominal
cramping limit its use
 H2-RECEPTOR
ANTAGONIST COTHERAPY
WITH A
NONSELECTIVE NSAID
 Standard
H2-receptor antagonist dosages (e.g.,
famotidine 40 mg/day) are effective in
reducing the risk of NSAID-induced duodenal
ulcer.
 Patients
with refractory ulcers should undergo
upper endoscopy to confirm a non healing
ulcer, exclude malignancy, and assess HP
status. HP-positive patients
 should receive eradication therapy
 In HP-negative patients, higher PPI dosages
(e.g.,
 omeprazole 40 mg/day) heal the majority of
ulcers.
 Continuous treatment with a PPI is often
necessary to maintain healing, as refractory
ulcers typically recur when therapy is
discontinued or the dose is reduced
 Poor
Patient compliance
 Resistant
organisms
 Increased
bacterial load
 Missed
dose in a 7 day regimen may also
contribute towards failure of eradication.
 Tolerability
 Preexisting
antimicrobial resistance.
 Proton
1.
2.
3.
4.
5.

1.
2.
pump inhibitors :
Diarrhea
Headache
Abdominal pain
Nausea and vomiting
Microscopic colitis
H2receptor antagonists :
Anti-androgeniceffects gynaecomastia.
Impotence
 Bismuth
1.

1.
2.

1.
2.
3.
4.

chelate:
Neurotoxicity
Sucralfate :
Constipation
Hypophosphataemia
Prostaglandin analogs :
Diarrhea
Abdominal cramps
Uterine bleeding
Abortion
Antacids : alkalosis, increase sodium load.
CONSQUENCE OF PROLONGED HYPOCHLORHYDRIA
PPI’s are metabolised by cytochrome p450
isoenzymes,the affinity of individual proton pump
inhibitors for these enzymes influence the incidence of
clinically relevant drug interactions.
 E.g. omeprazole+warfarin
warfarin levels.

benzodiazepines + omeprazole
benzodiazepines
levels.
 PPI’s also alter the absorption of other drugs du to
altered pH
 E.g. decreased absorption of Ketoconazole

increased absorption of Digoxin

Cimetidine interacts with Thiophylline, Diazepam,
Flurazepam, Triazolam.
 All acid suppressing drugs decrease absorption of pH
dependent control release tablets.
 Antacids interact with tetracyclines, ciprofloxacin
forming insoluble complexes or chelates.

 Weight loss
 Avoid spicy foods
 Avoid hot beverages
 Maintain optimum time interval between
 Reduce psychological stress
 Reduce physical stress
 Cut off irregular eating habits
 Educate the patient about the current
meals
principles of therapeutic management
 Patient should be warned about the specific
side effects to be expected from the regimen
and what to do if they experience any of these
side effects.
 Avoid drugs e.g. TCA’s, CCB’s, Anticholinergics,
NSAIDS.
 Pharmacotherapy
by Dipiro
 Clinical
Pharmacy and Therapeutics by
Roger Walker
 Pharmacology
 Clinical
by Thripati
Medicine by Kumar and Clark
 Pathology
By Harsh Mohan
Gastro-oesophageal
reflux disease
is the term used to describe a
histopathological alteration
resulting from episodes of reflux
of acid , pepsin and occasionally
bile into the oesophagus from the
stomach.
 Pathogenesis
 abnormal
:
reflux of gastric contents from the
stomach into the esophagus.
 Decreased gastroesophageal sphincter
pressures related to spontaneous transient
LES relaxations, transient increases in
intraabdominal pressure, all of which may
lead to the development of
gastroesophageal reflux.
 Other
factors : mucosal resistance, gastric
emptying, epidermal growth factor, and
salivary buffering.
 Abnormal oesophageal acid clearence.
 Endoscopy-negative reflux disease : GORD
with normal endoscopy.
 Hiatus hernia
 Patients
should be assessed for symptoms,
such as heartburn and for signs and symptoms
of complications (e.g., dysphagia)that require
immediate medical attention.
 The
goals of GERD treatment are to alleviate
symptoms, decrease the frequency of recurrent
disease, promote healing of mucosal injury, and
prevent complications.
 Many
patients with GERD will relapse if
medication is withdrawn,so long-term
maintenance treatment may be required.A
proton pump inhibitor is the drug of choice for
maintenance of patients with moderate to
severe GERD.