DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

might induce expression of COX-2. However, the nature of this interaction
is poorly understood, as are its therapeutic consequences.
Alzheimer’s Disease. Observational studies have suggested that
NSAID use, in particular ibuprofen, is associated with lower risk of
developing Alzheimer’s disease. However, more recent prospective
studies, including a randomized, controlled clinical trial comparing
celecoxib, naproxen, and placebo (ADAPT Research Group, 2008),
did not find a significant reduction in Alzheimer’s dementia with the
use of NSAIDs.
Adverse Effects of NSAID Therapy
Common adverse events that complicate therapy with
aspirin and NSAIDs are outlined in Table 34–2. Age
generally is correlated with an increased probability of
developing serious adverse reactions to NSAIDs, and
caution is warranted in choosing a lower starting dose
for elderly patients. NSAIDs are labeled with a black
box warning related to cardiovascular risks and are
specifically contraindicated following coronary artery
bypass graft (CABG) surgery.
Gastrointestinal. The most common symptoms associated
with these drugs are gastrointestinal, including
anorexia, nausea, dyspepsia, abdominal pain, and diarrhea.
These symptoms may be related to the induction
of gastric or intestinal ulcers, which is estimated to
occur in 15-30% of regular users. Ulceration may range
from small superficial erosions to full-thickness perforation
of the muscularis mucosa. There may be single or
multiple ulcers, and ulceration may be uncomplicated
or complicated by bleeding, perforation, or obstruction.
Blood loss can be gradual, leading to anemia over time,
or acute and life-threatening. The risk is further
increased in those with Helicobacter pylori infection,
heavy alcohol consumption, or other risk factors for
mucosal injury, including the concurrent use of glucocorticoids.
Although there is a perception that tNSAIDs
vary considerably in their tendency to cause erosions
and ulcers, this is based on overview analyses of small
and heterogeneous studies, often at single doses of individual
tNSAIDs.
Large-scale comparative studies of tNSAIDs have not been
performed, and there is no reliable information on which to assess
the comparative likelihood of GI ulceration on anti-inflammatory
doses of aspirin versus tNSAIDs. Thus, most information is derived
from the use of surrogate markers or from epidemiological data sets
and suggests that the relative risk for serious adverse GI events is
elevated about 3-fold in tNSAID users compared to non-users.
Epidemiological studies suggest that combining low-dose aspirin
(for cardioprotection) with other NSAIDs synergistically increases
the likelihood of GI adverse events (see “Drug Interactions”).
Similarly, the combination of multiple tNSAIDs and high dosage of
a single tNSAIDs (including inappropriately high dosage in the
Table 34–2
Common and Shared Side Effects of NSAIDs
SYSTEM
GI
Platelets
Renal
Cardiovascular
CNS
Uterus
Hypersensitivity
MANIFESTATIONS
Abdominal pain
Nausea
Diarrhea
Anorexia
Gastric erosions/ulcers a
Anemia a
GI hemorrhage a
Perforation/obstruction a
Inhibited platelet activation a
Propensity for bruising a
Increased risk of hemorrhage a
Salt and water retention
Edema, worsening of renal function
in renal/cardiac and cirrhotic
patients
Decreased effectiveness of
antihypertensive medications
Decreased effectiveness of diuretic
medications
Decreased urate excretion
(especially with aspirin)
Hyperkalemia
Closure of ductus arteriosus
Myocardial infarction b
Stroke b
Thrombosis b
Headache
Vertigo
Dizziness
Confusion
Hyperventilation (salicylates)
Prolongation of gestation
Inhibition of labor
Vasomotor rhinitis
Angioneurotic edema
Asthma
Urticaria
Flushing
Hypotension
Shock
a
Side effects decreased with COX-2-selective NSAIDs. b With the
exception of low-dose aspirin.
elderly) has been found to raise the risk for ulcer complications
by 7- and 9-fold, respectively. Age >70 years alone increases the
likelihood of complications almost 6-fold. The risk of ulcer complications
is increased in patients with past uncomplicated (6-fold) or
complicated ulcers (13-fold), or concurrent drug therapy including
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CHAPTER 34
ANTI-INFLAMMATORY, ANTIPYRETIC, AND ANALGESIC AGENTS; PHARMACOTHERAPY OF GOUT