Drug-induced Gastrointestinal Diseases Flashcards
Drug-induced Gastrointestinal Diseases
Clinical manifestations include
ulceration, diarrhea, constipation, hepatic and cholestatic diseases, pancreatitis, nausea, vomiting and anorexia
Tablets and capsules can get lodged within the esophagus, causing direct mucosal damage. An important warning sign
is a dull, aching pain in the chest or shoulder after taking the drug
esophageal injury is often characterized by
odynophagia (painful swallowing) or dysphagia (difficulty swallowing).
If potentially toxic substance stays in contact with the esophageal mucosa for a sufficiently long period of time, it can cause
“pill esophagitis”
order of Distribution of medications associated with drug-induced esophageal injury
NSAIDs
tetracyclines
potassium chloride
….
Pill esophagitis occurs most commonly in patients who take their medications with insufficient quantities of ___ or while lying down.
water
antiretroviral drug, HIV-1 protease inhibitor
Nelfinavir (Viracept)
Gl side effects of
Nelfinavir (Viracept)
when a drug gets lodged in your esophagus and its removed via endoscopy, you may still develop at the site where the drug had been lodge obstructing the esophagus.
This could be traversed only after dilation with a pediatric scope.
stricture (narrowing)
the drugs most commonly associated with drug-induced GI injury.
NSAIDs
The anti-inflammatory effects of NSAIDs are largely attributable to inhibition of ___, and their upper GI side-effects to inhibition of prostaglandin synthesis in the gastric mucosa, mediated via ___.
COX-2
COX-1
The antiplatelet effects of NSAIDs, valuable in cardioprotection, also result from inhibition of ___, with aspirin having the most pronounced antithrombotic effect of
COX-1
The mechanisms through which NSAIDs produce damage in the GI tract can be subdivided into __ (topical) actions and __ actions
local
systemic
Dual injury hypothesis
direct toxic effect on GI mucosa
and indirect systemic effects through active hepatic metabolites and decrease in mucosal prostaglandins
Systemic effects on the synthesis of mucosal prostaglandins have predominant :
different routs of administration and enteric-coated aspirin in order to prevent topical mucosal injury have failed to prevent the development of _____.
ulcers
direct effects of NSAIDs
hyperemia
erosions
sub-epithelial hemorrhage
systemic effects of NSAIDs lead to inhibition of
prostaglandins
bicarbonate
mucus production
characteristics of COX -___:
impairs platelet aggregation
reduces mucus and bicarb secretion
reduce mucosal blood flow
1
characteristics of COX -___:
reduces angiogenesis
increased leukocyte adherence
2
3 main types of GI lesions
-Superficial damage
-Endoscopically documented
non-symptomatic (silent)
-Symptomatic ulcers causing complications (GI hemorrhage)
Even a __ dose of aspirin is associated with a markedly increased risk for developing bleeding ulcers
low
__ increase the risk of upper GI bleeding possibly by decreasing platelet serotonin and interfering with platelet aggregation
SSRIs
this Protective Strategies in Preventing NSAIDs-induced Ulcers utilizes the lowest dose possible
In addition, concomitant use of other agents known to increase the risk of upper GI ulceration (low dose aspirin, anticoagulants, corticosteroids, SSRIs) should be avoided.
Low-risk
this Protective Strategies in Preventing NSAIDs-induced Ulcers suggests:
concomitant acid suppression therapy should be considered: proton pump inhibitors (PPI), misoprostol (synthetic prostaglandin E1 (PGE1) analogue)
moderate to high risk
To prevent NSAID-mediated adverse effects on the GI tract, the use of a selective ____ inhibitor (celecoxib), may be considered in some patients
COX-2
is the only COX-2 inhibitor licensed for use in the US
Celecoxib
COX-2 is also found in the __ endothelium, where it generates prostacyclin, which inhibits platelet aggregation and has vasodilator properties
vascular
stops the COX-2-mediated production of prostacyclin, which can result in increased platelet aggregation
COX-2 inhibitor
___ accounts for 7% of all adverse drug effects
over 700 drugs have been implicated in causing this
diarrhea
diarrhea
excessive amounts of solutes present in the intestinal lumen, which interfere with absorption of water
Osmotic diarrhea
-excessive endogenous fluid secretion by enterocytes and colonocytes
Secretory diarrhea
may cause diarrhea due to transit times that are too brief to complete fluid and electrolyte absorption
Rapid intestinal motility
mechanism of erythromycin, cisapride
motility diarrhea - short transit time
mechanism of antimicrobials AAD
pseudomembranous colitis - bacterial proliferation
mechanism of anti-neoplastics CTID
exudative diarrhea - protein losing enteropathy
Occurs in ~ 5-25% of the patients receiving antibiotics.
resolves after discontinuation of the antibiotic
Antibiotic associated diarrhea (AAD)
Gram-positive spore-former, survives under harsh conditions and during antibiotic therapy
C. difficile CDAD
Clinically significant strains of C. difficile produce __ exotoxins, which have been shown to disturb the function of the intestinal epithelium
2
antibiotics associated with C. difficile CDAD
Clindamycin, ampicillin, amoxicillin, quinolones and the cephalosporins
C. difficile CDAD ranges from a few days of intestinal fluid loss to life-threatening ____________
pseudomembranous colitis (PMC)
is associated with intense inflammation and dilated and damaged crypts covered by exudates of neutrophils, mucus and fibrin, which form the yellow membrane
pseudomembranous colitis (PMC)
Treatment of C. difficile CDAD
discontinuation of the offending antibiotic if possible, fluid and electrolyte replacement
antimicrobial therapy is indicated for patients with moderate to severe disease or with significant coexisting conditions. some examples are : (3)
vancomycin, metronidazole, or bacitracin
Many __ agents and supplements are known to induce diarrhea:
herbal
__ is the most common digestive symptom in the US
3 times more common in women than in men
Constipation
Drugs that result in the following:
Prolongation of intestinal transient time (reduced peristalsis)
Increased anal sphincter tone
Increased electrolyte and water reabsorption
Impaired defecation response
Opioids and related compounds
these drugs have Parasympatholytic actions affecting innervation of many regions of the gastrointestinal tract
Drugs with anticholinergic properties (antihistamines, antidepressants, antiparkinsonian agents, antispasmodics, and antipsychotics)
inhibit the activity of parasympathetic nervous system, mainly through preventing ACh from binding to the M2 receptors in the gut
Anticholinergics
Many patients with ____ disease are prone to constipation and this is often exacerbated by their medications.
Parkinson Disease (PD)
__ ____ receptors in the brain mainly modulate pain perception, while those in the GI tract have been shown to interfere with bowel motility.
Mu opioid
the following occurs upon activation of which receptor:
reduced activity of the myenteric plexus =>
decreased tone of the longitudinal smooth muscles, but increased tone of circular smooth muscles => substances stay in the intestine for longer time =>
more water is absorbed
Activation of peripheral m receptors
indicated for the treatment of opioid-induced constipation in patients with advanced illness (e.g., cancer, AIDS)
Methylnaltrexone
has been approved to accelerate recovery from postoperative gastrointestinal dysfunction following partial large or small bowel resection
Alvimopan
