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\begin{document}

\title{Sumatriptan poisoning and its clinical presentation in humans: a case
report}



\author[1]{peyman Erfantalab}%
\author[2]{Laya Ohadi}%
\author[3]{Farbod Amiri}%
\author[1]{Shahin Shadnia}%
\author[1]{Babak Mostafazadeh}%
\author[4]{Mehdi Forouzesh}%
\author[4]{Mohammad Javad Hedayatshodeh}%
\author[1]{Mitra Rahimi}%
\affil[1]{Toxicological Research Center, Clinical Toxicology Department, Loghman Hakim Hospital, School of Medicine, Shahid Beheshti Universiry of Medical Sciences, Tehran, Iran.}%
\affil[2]{Shahid Beheshti University of Medical Sciences}%
\affil[3]{Shahid Beheshti University of Medical Sciences, Tehran, Iran.}%
\affil[4]{Iranian Legal Medicine Research Center, Tehran, Iran.}%


\vspace{-1em}



  
  \date{May 15, 2024}


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\begin{abstract}
This case report displays some of the possible complications of
sumatriptan poisoning, including nephritic syndrome.%
\end{abstract}%



\sloppy


\textbf{Sumatriptan poisoning and its clinical presentation in humans: a
case report}

\textbf{Abstract}

This case report displays some of the possible complications of
sumatriptan poisoning, including nephritic syndrome.

\textbf{Key message}

This study aims to demonstrate some of the adverse effects related to
sumatriptan toxicity; a drug is used to treat migraine. Other studies
are required to reveal these side effects, especially for patients with
underlying diseases such as chronic kidney disease.

\textbf{Introduction}

One of the most prevalent and socioeconomically impactful disabling
primary headache is migraine, and its acute daily attacks can be treated
by prescription of sumatriptan orally or subcutaneously (1, 2).

This potent drug acts on 5-HT1 receptors, leading to vasoconstriction.
Like other medications, it has side effects like tachycardia, transient
hypertension, behavioral instability, facial edema, angle-closure
glaucoma, cardiac arrhythmias, abdominal pain, bloody diarrhea because
of vascular ischemia, splenic infarction, hepatotoxicity, and Raynaud's
syndrome (3-6).

Previously, Owen et al. revealed side effects of sumatriptan poisoning
in rodents and dogs. Moreover, Mobasheran et al. demonstrated renal
injury by activating nitric oxide synthase in rats induced by
sumatriptan, but there is no available information in humans (3, 5, 7).
This case report presents a case with sumatriptan poisoning who had
complications including nephritic syndrome.

\textbf{Case Presentation}

In February 2022, a 20-year-old bodybuilder man presented to the
emergency department with unusual sweating, agitation, hallucination,
and urine and fecal incontinency. He was admitted to the toxicology ward
due to the injection of 30 vials of sumatriptan (each vial is
6milligram/0.5milliliter solution) 2 days before his admission. He had
no complaints, such as respiratory difficulties or chest pain.

Past medical and habitual history for any drug or substances were
negative. At admitted time, vital signs demonstrated high blood pressure
(150/90 millimeter of mercury) and tachycardia (126 per minute). On the
other hand, respiratory rate (18 per minute), temperature (37.1\selectlanguage{ngerman}°
Celsius,) and oxygen saturation (99\%) were normal. Moreover, the
initial Glasgow coma scale (GCS) was 15/15.

According to the protocol, primary conservative treatment was started
for this patient. After a few hours, he became unconscious (GCS=9/15)
and was intubated.

Laboratory findings displayed hypernatremia and increased creatinine,
liver function markers, creatine phosphokinase (CPK), lactate
dehydrogenase (LDH), and D-dimer level. Qualitative measurement of
cardiac biomarkers such as troponin was also positive in this patient.
Besides, hematuria (3+) and proteinuria (2+) were detected in the urine
analysis but his urine drug test was negative for morphine, tramadol,
methadone, and tetrahydrocannabinol, amphetamine, and methamphetamine.
Laboratory tests are described in Table1.

Additionally, normal sinus rhythm was detected in his electrocardiogram
(ECG). Full cardiac monitoring and serial ECG and troponin were
performed for him because of positive troponin. Computed tomography (CT)
angiography was requested because pulmonary embolism (PE) was suspected
but was not performed due to hemodynamic instability. In order to high
suspicion, treatment for PE was started as soon as possible. Despite
advanced medical treatment, the cardiopulmonary arrest happened after
six days.

At autopsy, the lungs were dilated with purulent discharge, and a
normal-sized heart was observed with no apparent stenosis in coronary
arteries and no fibrosis and hyperemia in myocardial sections. Besides,
abnormalities were not found in the liver, spleen, or kidneys. Cerebral
edema due to hypoxia was detected in the brain with normal consistency.
Moreover, post mortem toxicological assessment had no scientific value
due to more than 6 days of hospitalization.

Consequently, hypernatremia, positive troponin, elevated level of
creatinine, liver enzymes, CPK and LDH, hematuria, and proteinuria were
associated with sumatriptan poisoning.\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Markers & Value w/Units & Normal range\tabularnewline
\midrule
\endhead
Urea & 3.3~mmol/L & 2.8--8.1\tabularnewline
Creatinine & \textbf{1.7~mg/dL} & 0.7-1.3\tabularnewline
Sodium & \textbf{153~mmol/L} & 136--145\tabularnewline
Potassium & 4.5~mmol/L & 3.5--5.1\tabularnewline
White blood cell count & 10 \selectlanguage{ngerman}×10\textsuperscript{3}/ul &
4.0--10.0\tabularnewline
Hemoglobin & 15 gram/dL & 13.2--16.6\tabularnewline
Platelet count & 321 \selectlanguage{ngerman}×10\textsuperscript{3}/ul & 150-400\tabularnewline
Calcium & 9.1~mg/dL & 8.6-10.3\tabularnewline
Magnesium & 1.05~mmol/L & 0.66--1.07\tabularnewline
Albumin & 4.7 gram/dL & 3.4-5.4\tabularnewline
Aspartate aminotransferase & \textbf{157 U/L} & 10-40\tabularnewline
Alanine aminotransferase & \textbf{359 U/L} & 7-56\tabularnewline
Alkaline phosphatase & \textbf{219 U/L} & 30-120\tabularnewline
Creatine phosphokinase & \textbf{2620 U/L} & 39-308\tabularnewline
Lactate dehydrogenase & \textbf{1448 U/L} & 140-280\tabularnewline
PH & 7.39 & 7.35-7.45\tabularnewline
PCO2 & 44.8 mmHg & 35-45\tabularnewline
HCO3 & 27.4 mEq/L & 22-28\tabularnewline
PT & 13.3 seconds & 11-13.5\tabularnewline
PTT & 26.7 seconds & 25-35\tabularnewline
INR & 1.1 & \textless{}1.1\tabularnewline
\bottomrule
\end{longtable}

Table1. Laboratory findings at admitted time

\textbf{Discussion}

Sumatriptan, a potent drug with a vasoconstriction effect prescribed in
the treatment of migraine attacks; can cause minor complications,
including sweating, transient hypertension, tachycardia, behavioral
changes, fatigue, sleepiness, and skin reaction (5). Similarly, our case
presented with a significant rise in blood pressure level and heart
rate. Moreover, agitation and hallucination were seen in this patient.
On the other hand, despite injecting 30 vials of sumatriptan, no
reaction at the injection site was detected. Persistent to our study,
Owen et al. demonstrated tachycardia induced by sumatriptan in animals
as well (3). Some of these complications are related to serotonin
syndrome, a drug-induced syndrome associated with sumatriptan
administration (8).

This effective drug has major adverse effects such as hepatotoxicity by
causing oxidative stress in hepatocytes (6). Besides, an increased level
of liver enzymes was identified in this patient that which is a sign of
affecting the liver.

Additionally, urine and fecal incontinency were realized in this case.
Another study on rabbits proved that drugs that act on 5-HT1 receptors
have regulatory action on bladder activity (9). On the other hand, there
is no available data about this pivotal effect on humans.

Increased creatinine level was detected in this case that, previously
proved by Mobasheran et al. In 2019, they performed a trial on rats that
revealed the administration of sumatriptan induces renal injury by
activating nitric oxide synthase and oxidative responses (7). In
addition, bilateral renal infarction, a rare side effect, was recognized
in a healthy 45-year-old woman after prescribing sumatriptan (10).
Additionally, Sharma et al. reported renal cortical infarction induced
by sumatriptan in a kidney allograft recipient (11). On the other hand,
Sheibani et al. displayed that the prescription of low doses of
sumatriptan in male rats has protective effects on renal injury because
of its anti-inflammatory agents (12).

Previously, Kelly displayed that one dose of sumatriptan can cause
sudden cardiac arrest because of coronary artery vasoconstriction (13).
Despite positive troponin, and increased level of LDH and CPK, there was
no positive clue about myocardial infarction in our patient according to
the biopsy.

\textbf{Conclusion}

Sumatriptan, that is used to treat migraine episodes, can affect many
systems in healthy humans, including cardiovascular system, causing
myocardial infarction (14). There are some studies about the toxicity of
this drug just in animals (3). Our case supports the novel complications
of sumatriptan toxicity in humans, including urine incontinency,
nephritic syndrome, and hepatotoxicity. Further clinical trials are
required to reveal the complications of the sumatriptan, especially in
patients with positive past medical history.

\textbf{Abbreviations}

Glasgow coma scale: GCS, creatine phosphokinase: CPK, lactate
dehydrogenase: LDH, electrocardiogram: ECG, computed tomography: CT,
pulmonary embolism: PE.

\textbf{Acknowledgments}

The authors appreciate medical staff of the intensive care unit at
Loghman Hakim Hospital.

\textbf{Authors' contributions}

PE collected the data, corrected the manuscript for its scientific
basis. LO collected the data for the study and wrote the manuscript. FA
wrote and corrected the manuscript for its scientific basis. SS and BM
revised the manuscript for grammar and syntax mistakes. MR corrected the
manuscript for its scientific basis and revised the manuscript for
grammar and syntax mistakes. MF and MJH collected and wrote the autopsy
part. All authors read and approved the final manuscript.

\textbf{Funding}

No additional funding for the execution of the present study was
received.

\textbf{Availability of data and materials}

The data and materials used in the current study are available from the
corresponding author on reasonable request.

\textbf{Ethics approval and consent to participate}

The patient's family consent has been taken, and consent form is with
the editor and available on request.

\textbf{Consent for publication}

Written informed consent was obtained from the patient's family to
publish this case report and any accompanying images. A copy of the
written consent is available for review by the journal's
Editor-in-Chief.

\textbf{Competing interests}

The authors declare that they have no competing or conflict of
interests.

\textbf{References}

1. Kaube H, May A, Pfaffenrath V. Sumatriptan. BMJ: British Medical
Journal. 1994;308(6943):1573.

2. Eigenbrodt AK, Ashina H, Khan S, Diener H-C, Mitsikostas DD, Sinclair
AJ, et al. Diagnosis and management of migraine in ten steps. Nature
Reviews Neurology. 2021;17(8):501-14.

3. Owen K, Hartley K, Tucker M, Parkinson M, Tweats D, Jackson M. The
preclinical toxicological evaluation of sumatriptan. Human \&
experimental toxicology. 1995;14(12):959-73.

4. Laine K, Raasakka T, M\selectlanguage{ngerman}äntynen J, Sakko P. Fatal cardiac arrhythmia
after oral sumatriptan. Headache: The Journal of Head and Face Pain.
1999;39(7):511-2.

5. Brar Y, Hosseini SA, Saadabadi A. Sumatriptan. StatPearls
{[}Internet{]}. 2021.

6. Fard JK, Hamzeiy H, Sattari M, Eghbal MA. Protective roles of
N-acetyl cysteine and/or taurine against sumatriptan-induced
hepatotoxicity. Advanced Pharmaceutical Bulletin. 2016;6(4):627.

7. Mobasheran P, Rajai N, Kohansal P, Dehpour AR, Shafaroodi H. The
effects of acute sumatriptan treatment on renal ischemia/reperfusion
injury in rat and the possible involvement of nitric oxide. Canadian
Journal of Physiology and Pharmacology. 2020;98(4):252-8.

8. Shapiro RE, Tepper SJ. The serotonin syndrome, triptans, and the
potential for drug--drug interactions. Headache: The Journal of Head and
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9. Lychkova AE, Pavone LM. Role of serotonin receptors in regulation of
contractile activity of urinary bladder in rabbits. Urology.
2013;81(3):696. e13-. e18.

10. Abramovitz B, Leonberg-Yoo A, Bahrainwala JZ, Litt H, Rudnick MR.
Bilateral renal infarctions during the use of sumatriptan. Kidney
international reports. 2018;3(5):1233-6.

11. Sharma SG, Post JB, Herlitz LC, Markowitz G. Renal cortical
infarction following treatment with sumatriptan in a kidney allograft
recipient. American journal of kidney diseases. 2013;61(2):326-9.

12. Sheibani M, Faghir-Ghanesefat H, Azizi Y, Mokhtari T, Yousefi\selectlanguage{english}-Manesh
H, Badkoubeh RS, et al. Anti-inflammatory and antioxidative effects of
sumatriptan against doxorubicin-induced cardiotoxicity in rat. Acta
Medica Iranica. 2021;59(7):406.

13. Kelly KM. Cardiac arrest following use of sumatriptan. Neurology.
1995;45(6):1211-3.

14. Mueller L, Gallagher RM, Ciervo CA. Vasospasm\selectlanguage{english}-lnduced Myocardial
Infarction With Sumatriptan. Headache: The Journal of Head and Face
Pain. 1996;36(5):329-31.

\textbf{Hosted file}

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