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CASE REPORT

cyclobenzaprine, overdose;
drug, overdose, cyclobenzaprine;
overdose, cyclobenzaprine

Overdose of Cyclobenzaprine,
The Tricyclic Muscle Relaxant

A case of cyclobenzaprine (Flexeril ) overdose in a 3I-year-old woman is William O'Riordan, MD


presented. The treatment rendered was analogous to treatment protocols Patrick Gillette, MD
implemented for tricyclic overdose. A review of the pharmacology of Juan Calderon, MD
Richard L Stennes, MD
cyclobenzaprine, as well as the management of patients who overdose on National City, California
this drug, is presented. [O'Riordan W, Gillette P, Calderon J, Stennes RL:
Overdose of cyclobenzaprine, the tricyclic muscle relaxant. Ann Emerg Med
From the Department of Emergency
May 1986;15:592-593.] Medicine, Paradise Valley Hospital,
National City, California.
INTRODUCTION
Cyclobenzaprine (Flexeril ) was first synthesized in 1961,1 and demon-
Received for publication June 6, 1985.
strated limited action as an antidepressant with no advantage over other tri- Revision received November 1, 1985.
cyclic antidepressants.2, 3 Subsequently it was found to act as a central Accepted for publication November 25,
muscle relaxant, 4-6 and it is now the most frequently prescribed muscl~e re- 1985.
laxant (personal communication, Russell Durbin, Merck, Sharp & Dohme,
June 1985). Address for Reprints: William O'Riordan,
Cyclobenzaprine is a tricyclic-like drug that requires immediate treatment 12882 Valley View, Suite 15, Garden
for acute intoxication.7 We present this case as an example. Grove, California 92645.

CASE REPORT
A 31-year-old woman was transported by ambulance after allegedly ingest-
ing 100 Motrin ~ tablets 24 hours prior to admission. Vital signs on admission
were as follows: blood pressure, 100/80 m m Hg; pulse, 122; respirations, 20;
and temperature, 36.1 C. The patient was disoriented to time, place, and
person and had slurred speech pattems. A supraventricular tachycardia of 132
beats per minute was found when the patient was examined by the emergen-
cy physician. Significant diagnostic studies were as follows: Hb, 15.2 gin%;
Hct, 44.9%; and WBC, 18,300 with 82% polymorphonuclear leukocytes, 9%
stabs, and 9% lymphocytes. Arterial blood gases were as follows: PO2, 123.5
torr; PCO2, 27.1 torr; pH, 7.228; and HCO3, 11.4 mEq/L. Electrolytes were as
follows: Na, 137 mEq/L; K, 4.2 mEq/L; C1, 106 mEq/L; and CO2, 15 mEq/L.
In the emergency department the patient was given 30 mL ipecac followed
by 250 mL water, resulting in emesis that did not include any pills or pill
fragments. A size 36 Ewald tube subsequently was passed into the patient's
stomach, and gastric lavage with normal saline was performed. Multiple pills
and large pill fragments were obtained. A total of 12 L fluid was used before a
clear return occurred. Subsequently 30 g activated charcoal followed by 3 oz
Fleets phosphate were administered through the tube.
During the patient's course, cardiac monitoring consistently revealed a su-
praventricular tachycardia of approximately 150 beats per minute. Because
the tachycardia did not respond to a fluid challenge of crystalloid solution,
the possibility of a tricyclic ingestion was entertained, and 150 mEq sodium
bicarbonate was administered 1Y. A repeat arterial blood gas revealed a pH of
7.34, and an additional 100 mEq of sodium bicarbonate was given. The pa-
tient was transferred to the intensive care unit.
Four hours after admission to the ED, results of a comprehensive tox-
icology screen became available and revealed the presence of cyclobenza-
prine. Because this was detected on a qualitative screen, no quantitative re-
sult was obtained.
Within 24 hours of transfer into the intensive care unit, the patient had a
marked decrease in urinary output, and the serum creatinine and BUN rose

15:5 May 1986 Annals of Emergency Medicine 592/137


CYCLOBENZAPRINE
O'Riordan et al

f r o m 1.1 mg% and 22 mg% to 5.9 comes possible to obtain tablet resi- pression (extensive study). A c t i v Nerv
mg% and 50 mg%, respectively. On dues despite significant time lapse Suppl 1965;7:290-291.
the first hospital day, a CPK of 9,400 after the ingestion of the medication. 3. Benesova O, Nahunek K: Correlation
IU/L was returned and a myoglobin Our experience has been that often between the experimental data from ani-
was reported to be positive. At the re- gastric lavage produces satisfactory re- mal studies and therapeutical effects of
quest of physicians at the patient's sults in cleansing the stomach. Ipecac, antidepressant drugs. Psychopharmaco-
prepaid hospital plan, the patient was in our experience, does not seem to be logia 1971;20:337-347.
transferred to another hospital in fair as effective as gastric lavage. This was 4. Share NN, McFarlane CS: Cycl0-
condition on her second hospital day. demonstrated in our patient. Ipecac benzaprine: A novel centrally acting skel-
She was lost to followup. was not effective in removing pill frag- etal muscle relaxant. Neuropharmacology
ments; lavage was. 1975;12:675-684.
DISCUSSION Ventricular arrhythmias, QRS wid- 5. Jones RF, Burke D, Morosszeky JE, et
Cyclobenzaprine is a muscle relax- ening, or intraventricular conduction al: A new agent for the control of spas-
ant that acts primarily within the cen- defects should be treated with sodium ticity. J Neurol Neurosurg Psychiatry
tral nervous system on an ill-defined bicarbonate 1 mEq/kg IV bolus and re- 1970;33:464-468.
portion of the brain stem. 4 Evidence peated if arrhythmias persist. 13 This
should be followed by IV infusion of 6. Ashby P, Burke D, Rao S, et al: Assess-
suggests that the net effect of cyclo- ment of cyclobenzaprine in the treatment
benzaprine is a reduction of both gam- sodium bicarbonate to produce an ar- of spasticity. J Neurol Neurosurg Psychia-
ma and alpha motor fiber systems, lo terial pH of 7.5.13 The mechanism of try 1972;35:599-605.
Toxic ingestions of cyclobenzaprine action of sodium bicarbonate is still
unknoxcvn. 13,14 7. Linden CH, Mitchiner JC, Lindzon RD,
can result in confusion, visual halluci- et al: Cyclobenzaprine overdosage. ] Tox-
nation, agitation, hyperreflexia, and The a d m i n i s t r a t i o n of physostig- icol Clin Toxicol 1983;20:281-288.
mine salicylate 1 to 3 mg IV may be
such anticholinergic effects as drow- 8. Flexeril prescribing information. West
siness, d r y m o u t h , and d i z z i n e s s . indicated to reverse the anticholiner-
gic effects of this drag.iS Because of Point, New York, Merck Sharp & Dohme,
Other manifestations m a y include a 1983.
m u l t i t u d e of cardiac a r r h y t h m i a s , its rapid metabolization and potential
miosis, severe hypotension, convul- toxicity, p h y s o s t i g m i n e s h o u l d be 9. Nibbelink DW, Strickland SC: Cyclo-
sions, stupor, and coma.7-1o Although used with u t m o s t care. Careful car- benzaprine (Flexeril): Report of a post-
diac and h e m o d y n a m i c m o n i t o r i n g marketing surveillance program. Curt
patients with tricyclic poisonings fre- Ther Res 1980;28:894-903.
quently manifest anhidrosis with hot- are required to manage any signs of
flushed skin, paradoxical diaphoresis cardiac toxicity and/or hypoten- 10. Biggs JT, Spiker D, Petit JM, et al: Tri-
sion. 14,15 cyclic antidepressant overdose: Incidence
has been reported in cyclobenzaprine
overdose. 11 of symptoms. JAMA 1977;238:135-138.
Cyclobenzaprine is closely related SUMMARY 11. Heckerling PS, Bartow TJ: Paradoxical
to tricyclic antidepressants both struc- This case is presented to ensure diaphoresis in cyclobenzaprine poisoning
t u r a l l y and p h a r m a c o l o g i c a l l y . 12 In that emergency health care profession- (letter). Ann Intern Med 1984;101:881.
keeping w i t h this similarity, cyclo- als realize that cyclobenzaprine is a 12. Baldessarini RJ: Tricyclic antidepres-
benzaprine has side effects in com- member of the tricyclic group even sants, in Goodman LS, Gilman A (eds):
m o n w i t h t h e t r i c y c l i c g r o u p of though it is marketed and advertised The Pharmacologic Basis of Therapeutics.
drugs. 12 It is, therefore, important for as a central muscle relaxant. Treat- New York, MacMillan Co, 1980, pp
it to be considered a tricyclic muscle m e n t of potentially lethal ingestions 418-427.
relaxant and not a tricyclic-like mus- may include administering gastric la- 13. Haddad LM: Tricyclic antidepres-
cle relaxant. vage, charcoal, and a cathartic, as well sants, in Tintinalli J (ed): A Study Guide
T h e m a n a g e m e n t of c y c l o b e n - as hemodynamic and cardiac monitor- in Emergency Medicine, vol 4. Dallas,
zaprine overdose should follow the ing, physostigmine salicylate, and al- American College of Emergency Physi-
prescribed treatment for overdose of kalinization of the patient's arterial cians, 1978, pp 4-14.
any tricyclic drug. lo T h e s t o m a c h pH to m i n i m i z e the anticholinergic 14. Rumack BM: Anticholinergic poison-
should be emptied immediately. We effects of toxic ingestion. ing: Treatment with physostigmine. Pedi-
have found gastric lavage to be most atrics 1973;52:449-451.
effective in cases of tricyclic overdose REFERENCES
1. Villani FJ, Ellis CA, Teichman C, et al: 15. Newton RW: Physostigmine salicy-
because the anticholinergic effects of late in the treatment of tricyclic anti-
cyclobenzaprine increase the time of J Med Pharm Chem 1962;5:373-383.
depressant overdosage. JAMA 1975;231:
gastric emptying and, therefore, it be- 2. Vinar D, Grof P: Proheptatriene in de- 941-943.

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