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CASE REPORT
Year : 2023 | Volume
: 24
| Issue : 4 | Page : 210-211
A case of ticagrelor-induced seizure
Fatih Selvi, Cihan Bedel, Bora Baltacioglu, Günay Yıldız
Department of Emergency Medicine, Health Science University, Antalya Training and Research Hospital, Antalya, Turkey
Correspondence Address:
Dr. Cihan Bedel
Department of Emergency Medicine, Health Science University Antalya Training and Research Hospital, Kazim Karabekir Street, Muratpasa, Antalya 07100
Turkey
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/heartviews.heartviews_20_23
Abstract
Ticagrelor is available as an oral antiplatelet agent that can bind reversibly to the adenosine diphosphate receptor P2Y12 on platelets without first having to be activated. Main side effects such as dizziness, bleeding gums, nausea in common, difficulty in speaking, fever, and change in mental status are rare. Herein, we report a patient who had seizures after the usage of ticagrelor.
Keywords: Oral antiplatelet agent, seizure, ticagrelor
Introduction 
Drug-induced seizure (DIS) is a well-characterized side effect in clinical studies. By definition, seizures are precipitated by the pharmacological and/or toxicological effects of a particular chemical entity after acute or chronic exposure or release of a drug.[1]
Given the high blood–brain barrier permeability of drugs, it shows the highest propensity for DIS. It is known that many pharmacological classes and therapeutic areas, especially antibacterial, antivirals, cardiovascular agents, immunosuppressives, and nonsteroidal anti-inflammatory drugs, may increase the risk of seizures.[2]
Ticagrelor is available as an oral antiplatelet agent that can bind reversibly to the adenosine diphosphate receptor P2Y12 on platelets without first having to be activated.[3] Main side effects such as dizziness, bleeding gums, nausea in common, difficulty in speaking, fever, and change in mental status are rare.[4] Herein, we report a patient who had seizures after the usage of ticagrelor.
Case Presentation An 84-year-old female had convulsions 10–15 times in the past 24-h period. Each convulsion lasted approximately 1 min. She had a history of coronary artery disease (CAD), heart failure, and kidney failure.
Due to CAD on April 12, ticagrelor 90 mg, two in a day, has been prescribed. She was prescribed doxazosin mesylate, carvedilol, atorvastatin calcium, acetylsalicylic acid, and allopurinol before. After the first usage of ticagrelor, the patient had convulsions. That's why she quit ticagrelor. After 10 days without ticagrelor, the patient's grandson gave ticagrelor to the patient by mistake. After the second time of usage, the patient had convulsions again. Then, she was taken to our emergency service with confusion and blood pressure of 174/86 mmHg. Other vital signs were normal.
She had previous inferior myocardial infarction findings on electrocardiography. Blood gas tests are normal except for lactate. Lactate was 5 mmol/L, sodium: 134 mmol/L, C-reactive protein: 18.4 mg/L, calcium: 8.8 mg/dL, potassium: 4.15 mmol/L, and glucose: 128. There was no evidence for pathological diseases on cranial computed tomography, magnetic resonance (MR), and diffusion MR.
In this patient, ticagrelor was considered the cause of the seizure because the history was consistent and other seizure causes were excluded. The patient was hospitalized with a prediagnosis of epilepsy to investigate the etiology of seizures.
Discussion Ticagrelor is an agent used to prevent serious or life-threatening heart attacks or strokes or death in people who have had a heart attack or have acute coronary syndrome. Ticagrelor is used for the first time to reduce the risk of heart attack or stroke in people at risk for CAD (decreased blood flow to the heart). Most of the patients do well with ticagrelor therapy.[5] Major bleeding, dyspnea, gastrointestinal disturbances, dizziness, nausea, shortness of breath, chest pain, bradyarrhythmias, swelling of the face, throat, tongue, lips, and eyes, and rash were reported as potential side effects.[6] To our knowledge, seizures associated with the use of ticagrelor have not been previously reported.
The main factors in the mechanism of drug-associated seizures are characterized by the patient and the drug. Personal factors, age, gender, hepatic or renal function status, predisposition to seizures, additional diseases, and drug use can be characterized. Another factor, drug related, can be considered the drug's property, blood–brain barrier penetration, on-target and off-target pharmacological activity on brain receptors/proteins, the major feature of the drug, dose level, route of administration, and lipophilicity.[7]
Drug-related factors are of particular interest during drug development because early wear is preferable to late-phase wear. Evaluation of neurological safety risks is important in new drug development. The etiology of drug-associated seizures appears to be largely the result of either inhibitor deficiency or increased excitatory signaling.[8] How this altered neuronal signaling occurs and how these changes interact with other changes in nonbrain receptor-driven drug-associated seizure, such as metabolic failure, electrolyte disturbances, altered drug metabolism, and withdrawal effects, remains poorly explained for most drugs. For this reason, it is necessary to investigate the seizure mechanism that may occur in newly developed drugs.[5],[6],[7],[8],[9] One of the most important agents among P2Y12 inhibitors, ticagrelor, has direct effects on adenosine metabolism.
Ticagrelor acts by blocking the reuptake of adenosine in cells. Increased adenosine levels can mediate local vasodilation and reduction of free radicals and pro-inflammatory molecules.[10] Downstream, adenosine receptor activation leads to cyclooxygenase-2 activation in addition to pro-survival kinases, for example, Akt and extracellular signaling regular kinase 1/2 mechanism of many side effects.[11] As in our case, drug-related seizures may be related to neurohumoral mechanisms.
Conclusion The seizure may be a rare but possible side effect of ticagrelor. Therefore, physicians should be aware of this rare side effect when using this drug.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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