| ESOPHAGUS:
Most common site of drug
injury - Mid esophagus.
Drugs dissolve & release caustic agents that can cause local damage.
Pills tend to stick at parts of anatomic narrowing .
Certain conditions may cause additional narrowing of the esophagus -
(heart disease with left atrial enlargement, aortic aneurysms,
enlarged thyroid, and enlarged lymph nodes ).
Adverse effects of drugs is also a problem in dysmotility disorders &
in the elderly.
Lesions:
-
Ulcers
: ( pin point lesions to large circumferential ulcers)
-
Strictures
:
due to potassium chloride, iron &
quinidine .
-Slowing of gastric emptying results in
acid reflux & reflux esophagitis.
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| STOMACH:
NSAIDs damage the
stomach by:
i) Direct local toxicity to the mucosa ii) By inhibition of
prostaglandin synthesis
Erosions and ulcers related are common.
Site: Antrum , body & along the greater curvature.
Gastric lesions related to NSAIDs:
Acute hemorrhagic
gastritis, erosions, ulcers, and chemical gastritis.
Acute hemorrhagic
gastritis : Damaged
surface epithelium, edema &hemorrhage of lamina propria & little
inflammation.
Chemical gastritis:
Foveolar hyperplasia producing corkscrew appearance with villiform
configuration. (Visit:
Chronic Gastritis
;
Helicobacter
pylori associated ( Type B) Gastritis ;
Autoimmune Gastritis
(Type A);
Reactive /Reflux/
Chemical Gastritis (Type C)
;
Prepyloric gastric
ulcers : often
multiple. Features of reactive gastritis in the adjacent mucosa.
Antral ulceration produce cicatrizing submucosal fibrosis &
prepyloric diaphragms.
Iron is locally corrosive and is associated with
erosions, ulcers,
and almost
infarct-like necrosis
of the gastric mucosa.
Fundic gland polyps
: In patients using proton pump inhibitors like omeprazole.
Endoscopically : small bubble like polyps in the body and fundic
mucosa.
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| SMALL
INTESTINE:
Drug induced lesions in
the small intestine:
Non-specific
ulceration: (rule
out Crohn's disease).Ileal ulcers may be:
(i) Single or multiple aphthoid and punched out ulcers.
(ii) Deeper ulceration with stricture formation.
(iii) Widespread erosion with pseudomembrane formation.
Histologically : surface consists of a layer of neutrophils, deep to
which is fibrinoid necrosis, granulation tissue formation & fibrotic
reaction.
Perforation:
Ileal ulcers may undergo perforation.
Stricture formation
& diaphragm disease
: NSAID induced ulcers may lead to stricture formation.
Diaphragm disease :
Associated with slow release NSAIDs and piroxicam. Common in the
distal ileum, proximal colon and jejunum. Gross: Composed of
multiple thin concentric luminal protrusions of fibrotic mucosa and
submucosa blocking the lumen with a small central opening.
Histologically : composed of mucosal folds with superficial ulceration
, chronic inflammation, vascular prominence & submucosal vertical
fibrosis.
(D/D: Absence of transmural inflammation & serosal changes rules out
Crohn's disease).
Malabsorption:
NSAIDs
have been associated with "NSAID enteropathy" (low grade GI blood
loss, protein loss, ileal dysfunction and malabsorption with changes
in intestinal permeability and inflammation). Other drugs associated
with malabsorption : Neomycin, progestational steroids & colchicine
Mefenamic acid
toxicity:
Hyperplastic crypts, partial villous atrophy, prominent enterocyte
vacuolation, no increase in intraepithelial lymphocytes and little
increase in inflammation in the lamina propria.
Progestational
steroid- villous
atrophy with hypoplastic crypts.
Neomycin-
Mild villous atrophy
Colchicine toxicity
(duodenum, jejunum & stomach): Increased numbers of metaphase mitoses,
epithelial pseudostratification and loss of polarity, and increase in
the proliferation zone (shown by Ki67 staining).
With therapeutic levels of colchicine - villous atrophy / hyperplasic
crypt pattern with increased mitotic figures of the jejunal mucosa.
COLLAGENOUS
COLITIS & LYMPHOCYTIC COLITIS :click
PSEUDOMEMBRANOUS COLITIS :
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| COLON:
Drug induced damage in the
colon :
1.Adverse
effect on pre-existing disease:-
NSAIDs associated with
complications to
diverticular disease
: GI hemorrhage, perforation, and fistulous tract formation.
Responsible for
exacerbating preexisting inflammatory bowel disease
(IBD).
Analgesics may bring about relapse of ulcerative colitis.
Immunosuppressive drugs in IBD may
provoke opportunistic
infection (Eg.
Cytomegalovirus.)
2. Cause de novo
disease:-
Ulceration &
perforation:
Solitary, non- specific
ulcers , usually present in the caecum following use of NSAIDs -(oxyphenbutazone,
diclofenac, ibuprofen), in the distal colon (naproxen, aspirin &
phenylbutazone) & anorectal region(indomethacin).
Stricures &
'diaphragm disease :
NSAIDs
Toxic megacolon
- methotrexate therapy
Mucosal necrosis:
Kayexalate (sodium polystyrene sulfonate) in sorbitol - induce
necrosis of the GIT. Administered orally or by enema in the treatment
of hyperkalemia. Resected, long segments of colon and rectum may be
necrotic.
Ischaemic colitis:
Associated with drugs that predispose to thrombosis (oral
contraceptives, estrogen) and drugs that cause vasoconstriction
(cocaine, amphetamines). Histologically characterized by damaged
epithelium ,decreased mucin and small shrunken crypts, dense pink
lamina propria and relatively little inflammation. Endoscopy may give
rise to mucosal damage in colon. Glutaraldehyde (to cleanse &
sterilize endoscopes) may produce colitis with ischaemic features.
Indian ink & methylene blue (mark areas of colorectal mucosa during
endoscopy) may produce ischaemia.
Acute "self
limited" colitis
associated with a number of drugs -diclofenac, naproxen, and
carbamazepine. Acute colitis is characterized by neutrophils in the
lamina propria and epithelium associated with reactive epithelial
changes but with minimal chronic inflammation or crypt distortion
(D/D- Inflammatory bowel disease ).
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