Final NSAIDs Induced Gastropathy.pptx

NSAIDs
Induced Gastropathy
& its management
Nonsteroidal anti-inflammatory drugs (NSAIDs)

What are NSAIDs
NSAIDs are more than just pain relievers. They also help
reduce inflammation and lower fevers. They prevent blood
from clotting, which is good in some cases but not so
beneficial in others.
NSAIDs are used to treat a variety of symptoms such as
pain, inflammation, and stiffness caused by rheumatoid
arthritis and tendonitis.

NSAIDs and their classification
Classification of NSAIDs
Types Chemical composition Common NSAIDs
Salicylates
Salicylates Derivatives of 2-
hydroxybenzoic acid (salicylic acid)
Aspirin, diflunisal, and salsalate
Propionic acid derivatives or
“profens”
Derivatives of arylacetic acids
Ibuprofen, dexibuprofen, ketoprofen, dexketoprofen,
naproxen, fenoprofen, flurbiprofen, oxaprozin, and
loxoprofen
Acetic acid derivatives Derivatives of acetic acids
Indomethacin, diclofenac, nabumetone,
tolmetin, sulindac, etodolac, and ketorolac
Enolic acid derivatives or
oxicams
Derivatives of 4-hydroxy benzothiazine
heterocycle
Piroxicam, isoxicam, meloxicam, tenoxicam,
droxicam, and lornoxicam
Fenamic acid derivatives or
fenamates
Derivatives of anthranilic acid
Mefenamic acid, flufenamic acid, tolfenamic
acid, and meclofenamic acid
Phenylpyrazolones
Derivatives of 1-aryl-3,5-
pyrazolidinedione
Phenylbutazone, oxyphenbutazone
COX-2 selective inhibitors Diaryl-5-membered heterocycles Celecoxib, rofecoxib, and valdecoxib
Anilides and sulphoanilides
Acetamides of aniline with or without a
4-hydroxy or 4-alkoxy group
Acetaminophen, phenacetin, and
nimesulide
Current perspectives in NSAID-induced gastropathy. Mediators of inflammation. 2013; 2013

NSAIDs in patient management
NSAIDs are used for three broad
symptom types that occur in a
range of conditions:
High temperature or fever
Inflammation
Pain
NSAIDs play a role in the treatment of many
different conditions that involve inflammation, pain
or both. Which includes:
Rheumatoid arthritis
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
Acute gout
Period pain
Metastatic bone pain
Osteoarthritis
Headache and migraine
Post-operative pain
Pain due to inflammation
and tissue injury
Renal colic
Anti-platelet properties

Risk factors for GI complications
associated with NSAID
Journal of Pain Research 2018:11 361–374

Relative risk of upper-GI complications
with different NSAIDs

The most commonly used drugs in
Trauma practice, for pain relief are
Non-Steroidal anti inflammatory drugs
(NSAIDs)
According to
Orthoinfo.aaos.org/topic.cfm?topic=a00284

NSAIDs Misuse and it’s impact
More than 30 million people take nonsteroidal
anti-inflammatory drugs (NSAIDs) each day.
This number has grown significantly with
increasing use of OTC and prescription NSAIDs,
low-dose aspirin, and after reports of their
potential antineoplastic effects.
The efficacy of NSAIDs as anti-inflammatory
analgesics is not in doubt, but their adverse
events are problematic. These relate mainly to
cardiovascular, renal, hepatic, and
gastrointestinal tissues.
Gastroenterology. 2018 Feb 1; 154(3): 500-14

NSAIDs Misuse and it’s impact
In a study aimed to determine the prescribing practice of multiple NSAIDs in
Pakistan by healthcare practitioner and their attitude towards patient life
safety and what consequences are responsible for irrational practice of these
most common OTC drug, their findings were:
Journal of Scientific and Innovative
Research. 2014; 3(2): 148-54

Impact of misuse on GI
The cardiovascular adverse events have recently received much attention, but the
frequency and severity of the gastrointestinal damage continues to cause concern.
Accordingly, gastroduodenal ulcer rates range from 5% to 80% in short-term
endoscopy studies and from 15% to 40% in long-term users.
NSAIDs also damage the small intestine as many as 70% of long-term users of
NSAIDs have small intestinal inflammation, and 30% have erosions or ulcers.
The gastric and small bowel damage is associated with various management
problems and, at times, life-threatening complications, such as bleeding, strictures
and perforations.
Gastroenterology. 2018 Feb 1; 154(3): 500-14

NSAIDs or no NSAIDs
Gastrointestinal effects of NSAIDs and coxibs. Journal of Pain and Symptom
Management. 2003 Feb 1;25(2):32-40

NSAID induced GI complications
There are mainly three different mechanisms of NSAID induced GI
complications:
Inhibition of enzyme COX-
1 and gastroprotective PG
Membrane
permeabilization
Production of additional
pro-inflammatory
mediators.

Standard-dose PPIs are recommended for patients taking ns-
NSAIDs at risk for upper-GI complications (bleeding and
perforation) and for those having had an episode of previous GI
bleeding and prescribed selective COX2 inhibitors. In both ns-
NSAID and COX2-selective NSAID users, PPI therapy reduces
upper-GI symptoms, in particular dyspepsia.
Appropriate use of PPIs: recommendations from
international guidelines
2016 Position paper on safe PPI use

The 2017 update recommends that patients take long-
term PPIs for NSAID bleeding prophylaxis if at high risk
American Gastroenterological Association
clinical practice updates 2017

In patients with NSAID-associated bleeding ulcers who must resume
NSAIDs, it is recommended to give a daily PPI together with a COX2-
selective NSAID at the lowest effective dose.
In patients with low-dose aspirin-associated bleeding ulcers that have
been resumed on aspirin for secondary prevention, long-term daily PPI
therapy should also be provided
American College of Gastroenterology
guidelines on management of bleeding ulcers

In patients using NSAIDs with diagnosed peptic ulcers, a full-dose PPI or
H2RA for 8 weeks should be offered and NSAIDs should be stopped where
possible.
In high-risk patients (previous ulceration) for whom NSAID continuation is
necessary, a PPI together with the NSAID should be prescribed.
National Institute for Health and Care Excellence 2014
guidelines on the investigation and management of
gastroesophageal reflux disease and dyspepsia in adults

Expert consensus document on reducing the risks of
antiplatelet therapy and NSAID use states that PPIs are the
preferred gastroprotective agent for the treatment and
prevention of GI toxicity associated with NSAIDs and aspirin
Recommendations - Risks of antiplatelet therapy and
NSAID use

Therapies for prevention of
Gastric Damage

Current perspectives in NSAID-Induced Gastropathy
Several clinical practice guidelines have proposed different approaches for
controlling the GI complications associated with NSAIDs.
A number of strategies have been recommended by American College of
Gastroenterology to decrease NSAID-induced GI damage including use of:
Selective cyclooxygenase-2 inhibitors,
Co-administration of gastroprotective agents like misoprostol
PPIs, or histamine-2 receptor antagonists.

As per the guidelines, PPIs recommended
for gastroprotective therapy to the patients
on thienopyridines and NSAIDs.

S Afr Pharm J 2012;79(4):12-18

Clinician’s Guide
The use of proton pump inhibitors in treating and preventing NSAID-
induced mucosal damage. Arthritis research & therapy. 2013 Jul 1;15(S3):S5

Method to prevent Peptic ulcer and
Mucosal injury in patients taking NSAID
Lanza et al. Am J Gastroenterol 2009; 104:728 – 738
• Although co-therapy with a standard-dose H2RA may prevent
duodenal ulcers, it has not been shown to prevent NSAID-
related gastric ulceration.
• Enteric coating or buffering of NSAIDs and co-therapy with
sucralfate have not been shown to be effective in
preventing NSAID-related gastric or duodenal ulceration

The risk of Gastroduodenal ulceration
associated with Non-steroidal anti-
inflammatory drugs (NSAIDs) can be
reduced by 75% in healthy individuals,
if they take Omeprazole 20 mg daily
According to study published in US Doctor’s
Guide of Gastroenterology
Oct 2007
75%

ENSURING GUT PROTECTION
The efficacy of omeprazole in the treatment of acid-related
disorders is well established.
Clin Drug Investig 2012; 32 (4): 221-233

OMNIUM TRIAL
OMNIUM
(Omeprazole versus
Misoprostol for NSAID-induced
Ulcer Management)
The remission rate was
significantly higher
with OMEPRAZOLE
than with the
comparator
Clin Drug Investig 2012; 32 (4): 221-233

Design: 6 month randomized, double blind, controlled trial.
Setting: 93 clinical centers in 14 countries.
Patients: 935 patients who were 18–85 years of age; had
conditions that required continuous treatment with at least a
minimal dose of oral or rectal NSAIDs; and had ulcers ⩾3 mm in
diameter in stomach, duodenum, or both, or >10 gastric or
duodenal erosions.
Ref: Hawkey CJ, Karrasch JA, Szczepañski L, et al. (1998) . N Engl J Med
Omeprazole (OM) vs. Misoprostol (MIS) for ulcers
associated with non-steroidal anti-inflammatory drug use

Hawkey CJ, Karrasch JA, Szczepañski L, et al. (1998) . N Engl J Med
Omeprazole 20 mg is was more effective than
Misoprostol
Omeprazole (20 mg/day)
was more effective and
better at maintaining
remission than Misoprostol
(400 μg/day).
Misoprostol caused more
adverse events during
treatment.

BioMed Research International Volume 2014, Article ID 693567, 7 pages
Comparison of Proton Pump Inhibitor and Histamine-2
Receptor Antagonist in the Prevention of Recurrent Peptic
Ulcers/Erosions in Long-Term Low-Dose Aspirin Users
The 24-week clinical outcomes of the patients using low-dose aspirin for
cardiovascular protection with a history of ulcers/erosions and co-therapy of
Omeprazole or Famotidine were retrospectively reviewed.
Design: Retrospective cohort study
Study design: Total 104 patients (Famotidine group: 49 patients, Omeprazole group:
55 patients)
Dosage:
• Aspirin 75 to 325 mg daily (For primary or secondary prevention of coronary artery disease or cerebral vascular
accident)
• Concomitant use of Famotidine 40 mg daily or Omeprazole 20 mg daily

Omeprazole is superior to Histamine-2 Receptor
Antagonist
49%
49% less gastrointestinal
symptoms with the use of
Omeprazole 20mg
70%
70% less recurrent
ulcers/erosions with the
use of Omeprazole 20mg
Ref: BioMed Research International Volume 2014, Article ID 693567, 7 pages

COX-2 NSAIDs versus conventional NSAIDs plus PPIs
Trial Design
• 287 H. Pylori Negative
patients whose Bleeding
peptic ulcer has healed.
• Recurrent bleeding over 6
months observation
Celecoxib 200mg BD
(s-NSAID) +
Placebo
Scheiman Arthritis Research & Therapy 2013, 15(Suppl 3):S5
Diclofenac 75mg (ns-
NSAID)
+
Omeprazole 20mg OD
4.9%
recurrent bleeding 6.4%
recurrent bleeding
A number of observational studies have provided support
for the value of PPI gastroprotection as an alternative
approach to the use of a COX-2 speciﬁc inhibitor.

RISK REDUCTION IN ULCER BLEEDING COMPARED TO
COX-2 INHIBITORS
In a large Tennessee Medicaid database, investigators
found:
Concurrent users of NSAIDs and PPIs had a 54% (27
to 72%) risk reduction in ulcer bleeding, very similar
to the 50% (27 to 66%) reduction for concurrent users
of PPIs and COX-2 selective inhibitors
Scheiman Arthritis Research & Therapy 2013, 15(Suppl 3):S5

1
NSAIDs are the
major cause of
Upper GI erosion,
ulcers and
bleeding
2
Omeprazole 20mg
OD with NSAID is
effective therapy for
upper GI erosions,
ulcers and bleeding
cases
3
Co-therapy with
Omeprazole 20mg
is effective therapy
to prevent GI
problems
Key Points

Final NSAIDs Induced Gastropathy.pptx

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