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Cyclobenzaprine is FDA-approved as an adjunct to rest for the treatment of muscle spasms associated with acute, painful musculoskeletal conditions. Cyclobenzaprine is a part of a group of medications referred to as cyclical antidepressants. Cyclobenzaprine is a tricyclic amine salt that works in the central nervous system (CNS) as a depressant that reduces muscle hyperactivity. These cyclical antidepressants have roles in treating depression, neuropathic pain, migraine prophylaxis, attention deficit hyperactive disorder, and potential muscle relaxation properties. In addition, this activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cyclobenzaprine for members of the interprofessional team who will potentially prescribe or encounter patients taking cyclobenzaprine. Objectives: Identify the mechanism of action of cyclobenzaprine. Review the FDA-approved indications for cyclobenzaprine. Outline the important potential adverse events with cyclobenzaprine. Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients for whom cyclobenzaprine is a therapeutic option. Access free multiple choice questions on this topic.

Cyclobenzaprine is structurally and pharmacologically related to tricyclic antidepressants. Among the most dreaded toxicities linked with cyclical antidepressants, overdoses affect fast-acting sodium channels in the cardiac conduction system. Cyclical antidepressants block the cardiac sodium channel and cause prolongation of cardiac depolarization, which manifests as QRS widening on electrocardiograms. There is also evidence that cyclical antidepressants may decrease the seizure threshold by interfering with chloride conductance on the GABA receptor. One study retrospectively looked at 750 charts at five regional poison centers between the years 1989 to 1993. Based on their retrospective study, the authors concluded that cyclobenzaprine in toxic doses less than 1000 mg does not appear to produce the life-threatening neurotoxicity and cardiotoxic dysrhythmias associated with traditional tricyclic antidepressants. The case report of cyclobenzaprine toxicity describes ileus and simultaneous ST segment elevations on EKG.[26] Other case reports, however, have implicated cyclobenzaprine in acute overdose as the culprit leading to fatalities. For example, there were two reported cases of overdoses in which elevated levels of cyclobenzaprine were found in postmortem evaluations of the patients. The authors, therefore, document an association linking elevated cyclobenzaprine levels with two examples of presumed fatal overdoses.[27] The most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia. Rare but potentially critical manifestations of overdose are cardiac arrest, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Changes in the electrocardiogram, particularly in the QRS axis or width, are clinically significant indicators of cyclobenzaprine toxicity.[20] To summarize, treatment beyond GI decontamination is unnecessary for less than 100 mg ingestions. Cyclobenzaprine does not appear to produce life-threatening cardiovascular or neurologic effects in doses less than 1000 mg, and serious toxicity such as arrhythmias, hypotension, and seizures occur at doses greater than 1000 mg.[28] Although rare, deaths may occur from overdosage(>1000 mg) with cyclobenzaprine. As management of overdose is complex, the clinician should contact a poison control center for the latest information on treatment. Management of Toxicity

To summarize, treatment beyond GI decontamination is unnecessary for less than 100 mg ingestions. Cyclobenzaprine does not appear to produce life-threatening cardiovascular or neurologic effects in doses less than 1000 mg, and serious toxicity such as arrhythmias, hypotension, and seizures occur at doses greater than 1000 mg.[28] Although rare, deaths may occur from overdosage(>1000 mg) with cyclobenzaprine. As management of overdose is complex, the clinician should contact a poison control center for the latest information on treatment. Management of Toxicity General measures include airway breathing and circulation To protect against potentially critical arrhythmias, obtain an EKG and quickly initiate cardiac monitoring Protect the patient’s airway, and establish an intravenous line Gastrointestinal Decontamination by large volume gastric lavage followed by activated charcoal Serum alkalinization using sodium bicarbonate if EKG exhibits QRS prolongation Dysrhythmias unresponsive to sodium bicarbonate and hyperventilation may respond to phenytoin, lidocaine, or bretylium In patients with CNS depression, early intubation because of the potential for sudden collapse Seizures control with benzodiazepines or, if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin) Physostigmine administration should be in close consultation with a poison control center[29]

Cyclobenzaprine is a commonly used medication to manage muscle spasms. While the drug is effective, it has many adverse effects; healthcare providers must understand proper indication, dosage, and toxicity management. Ideally, clinicians (MDs, DOs, NPs, PAs) initiate cyclobenzaprine for appropriate indication. Similarly, the dentist may prescribe cyclobenzaprine for pain associated with temporomandibular joint disorders. Pharmacists should ensure proper dosing and report to clinicians in case of drug interactions. Nurses should monitor the pain levels and counsel the patient on adherence to therapy. In case of acute cyclobenzaprine overdose, emergency medicine physicians and triage nurses should stabilize the patient. If EKG demonstrates QRS prolongation, the clinician should initiate sodium bicarbonate therapy. In severe overdose, ventricular arrhythmias and seizures may require MICU-level of care under the supervision of a critical care physician. As discussed above, the clinician should consider contacting the poison control center in refractory cases. A psychiatrist consult is required for deliberate poisoning of cyclobenzaprine. As illustrated above, multiple healthcare providers manage the patient on cyclobenzaprine therapy; hence, clinicians (MDs, DOs, NPs, PAs), specialists, physical therapists, pharmacists, nurses, and other healthcare providers should collaborate closely. The clinicians should use the communication tool SBAR (situation, background, assessment, and recommendation) to improve patient safety.[30] Excellent communication among healthcare providers can improve efficacy and minimizes adverse drug reactions related to cyclobenzaprine therapy. An interprofessional team approach translates to improved patient outcomes and satisfaction. [Level 5] A study on patients suffering from back pain concluded that clinicians could contribute to pain management through pharmacotherapy, red flag screening, and reassurance; physical therapists could play a crucial role in general exercise and motivation to stay active, and occupation therapists can focus on disability assessment. Thus an interprofessional team involving clinicians, physical therapists, and occupational therapists can significantly improve patient care.[31] [Level 5]