Clinical Therapeutics and the Recognition of Drug-Induced Disease
Case Study
NSAIDS in a Geriatric Patient
Presenting History
A 68 year old mildly obese female with known hypertension and
adult onset diabetes mellitus (DM) presents to the emergency room
(ER) complaining of chest pain and shortness of breath (SOB) of
3 days duration. She is currently taking digoxin, hydrochlorothiazide
(HCTZ), potassium chloride (KCl), cimetidine, tolazamide for 1
year and a new analgesic nonsteroidal anti-inflammatory drug (NSAID)
called "ALLPROFEN" for low back pain for the past 5
days. (Note: "ALLPROFEN" is a hypothetical new analgesic.)
The patient has no known drug allergies. Her physical exam is
unremarkable except for a presystolic cardiac extra sound (S4).
Her blood pressure is 150/90 sitting, heart rate is 80 and regular.
Lab: ECG shows LVH and nonspecific ST-T wave changes.
List at least four major possible
etiologies for chest pain in this patient.
- [Cardiac origin, e.g., coronary artery disease (CAD) or congestive
heart failure. The patient has a history of hypertension and adult
onset diabetes which are major risk factors for CAD. In addition,
she is taking digoxin and HCTZ consistent with previous history
of congestive heart failure.]
- [Noncardiac musculoskeletal chest wall pain.]
- [Noncardiac pain originating from the gastrointestinal tract
which can present as chest pain similar to cardiac disease. This
includes hiatal hernia with reflux esophagitis-gastritis, etc.
related to previous disorder (the patient is on cimetidine) or
a new problem related to the new NSAID.]
- [Pulmonary embolus]
List at least three important
points (positive or negative) that should be ascertained from
this patient's history regarding chest pain.
- [The PQRST symptom analysis of pain. This includes questions
about Provocative-palliative factors, Quality, Region, Severity,
and Temporal characteristics of pain.(26)]
- [Prior history of similar symptoms and clinical course (diagnosis
and treatment).]
- [If a specific disease entity is suspected, e.g., coronary
artery disease (CAD) or gastroesophageal reflux disorder, other
pertinent points might include family history of similar disorder
and compliance with current drug regimen related to cimetidine.]
Hospital/Home Course
She is admitted to the CCU for further observation. The ER physician
decides to maintain all of her current medications but discontinue
the new NSAID. The patient does well clinically over the next
24 hours. The cardiac enzymes are normal and the ECG remains unchanged.
The patient is then discharged home on her regular medications
except for the new NSAID. At home, the back pain returns 3 days
later. She decides to take the NSAID analgesic which had been
previously prescribed and goes to bed. Within 1 hour after taking
this medication, she develops dyspnea, wheezing, tightness and
pain in the chest which radiates to the left shoulder and down
her left arm.
She returns to the ER. The exam is essentially unchanged from
her previous visit except for some bibasilar rales. Her BP is
160/95. Heart rate is 90 and regular. ECG shows ST-T wave changes
consistent with ischemia.
List your top two etiologies
for chest pain and dyspnea.
- [Ischemic heart disease secondary to coronary artery disease.]
- [An ADE associated with ALLPROFEN. This is somewhat problematic
given the temporal sequence. One general mechanism for NSAID -
induced ADEs relates to their pharmacologic effect (inhibition
of prostaglandins) on the kidney leading to sodium and fluid retention.
This could theoretically precipitate congestive heart failure
and lead to nocturnal angina pectoris. It is doubtful, however,
that a single dose could produce this effect. However, more plausible
could be an allergic pulmonary drug reaction which could account
for the SOB and wheezing. The patient may have taken NSAIDs in
the past. Allergic reactions with NSAIDs are thought to involve
several mechanisms including pharmacologically mediated reactions
and an immune response to a chemical antigen or cross-sensitization
(i.e., classical anaphylaxis).]
If your list included an adverse
drug reaction, what should you do, if anything?
- [Treat the patient symptomatically for ischemic heart disease.
In addition, supportive therapy including nasal oxygen and possible
diphenhydramine should be considered for the possible allergic
drug reaction.]
- [Check relevant drug information sources such as the PDR for
previous reports of allergic reactions associated with ALLPROFEN.]
- [Report this possible allergic drug reaction to your hospital
drug monitoring committee even if you are not sure that is was
definitely an adverse drug reaction.]
Subsequent Course:
The patient is started on several new medications including nitroglycerin
and an ACE inhibitor. She is told to discontinue the NSAID and
to take acetaminophen prn for back pain.
Six months later, the patient undergoes arthroscopic chondroplasty
and a partial meniscectomy of the left knee under epidural anesthesia
with 2% mepivacaine. The anesthetic wears off and she complains
of throbbing knee pain 2 hours after the procedure. She receives
ketorolac 30 mg IM with prompt relief. Thirty minutes later the
patient is discharged, but collapses in the hospital lobby. The
hospital administrator who happens to be in the lobby calls code
"blue". The code team arrives and finds the patient
unresponsive, cyanotic, hypotensive (BP-50/30) with urticaria
and a palpable carotid pulse of 80.
List the two most likely causes
of her problem.
- [Anaphylactic shock secondary to ketorolac. The constellation
of sudden collapse associated with hypotension, wheezing, and
urticaria is classic. However, if urticaria was not present, then
an acute MI would be a real possibility.]
- [Acute MI with cardiogenic shock.]
An airway is established and she is started on O2 with
positive pressure ventilation. She regains consciousness and begins
to wheeze. Epinephrine (1 mg) is administered followed by IV fluids.
By the next day, the patient is stabilized with return of her
usual blood pressure and normal breathing.
You now think that the above syndrome of sudden collapse associated
with hypotension, urticaria and wheezing 30 minutes after taking
ketorolac may be drug related but you are not sure.
- What are your responsibilities
to report this suspected ADE to your hospital monitoring committee?
- [Clearly, this serious reaction needs to be reported even
if you are not absolutely sure it was caused by the drug in question.]
- What should the hospital
monitoring committee do about reporting this suspected ADE?
- [Clearly, this serious reaction should be reported to MEDWATCH/FDA.
This is true even if this kind of anaphylactic reaction has been
documented in the PDR and thus is a known ADE of ketorolac.]
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