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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 3  |  Issue : 1  |  Page : 60-62

Phenytoin toxicity secondary to friend's advice!!


1 Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, KSA
2 Department of Psychiatry, JSS Hospital, Mysore, Karnataka, India
3 Department of Pharmacy Practice, JSS College of Pharmacy, JSS University, Mysore, Karnataka, India

Date of Web Publication24-May-2019

Correspondence Address:
Dr. Jisha Myalil Lucca
College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam
KSA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_63_18

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  Abstract 


It is very common that antiepileptic prescription in substance induced seizure, however Phenytoin abuse is very rare. We report a case of 25 year old man with a known diagnosis of polysubstance abuse. After a road traffic accident and hospitalization, the patient reduced the use of various substances he used and eventualy lead to withdrawal seizures and started with Phenytoin 100 mg twice daily. As influenced by friend's advice he increased phenytoin dose and developed clinical symptoms of phenytoin toxicity.

Keywords: Abuse, phenytoin, toxicity


How to cite this article:
Lucca JM, Kishore, Shruthi. Phenytoin toxicity secondary to friend's advice!!. Ann Indian Psychiatry 2019;3:60-2

How to cite this URL:
Lucca JM, Kishore, Shruthi. Phenytoin toxicity secondary to friend's advice!!. Ann Indian Psychiatry [serial online] 2019 [cited 2019 Dec 12];3:60-2. Available from: http://www.anip.co.in/text.asp?2019/3/1/60/259098




  Introduction Top


The misuse of prescription medications is an increasing problem that is associated with serious medical harm and health service utilization.[1] In India, phenytoin is the most frequently prescribed medication for most forms of epilepsy (with the exception for absence seizures). Phenytoin intoxication can result from intentional overdose, inappropriate dosage adjustments, drug interactions, or physiological changes that result in altered pharmacokinetics in the setting of chronic therapy.[2],[3] The manifestations of toxicity are dose-dependent, and withdrawal of the drug usually results in complete resolution of the signs of toxicity.[4],[5],[6] Phenytoin abuse or misuse is extremely rare. Reported here is a case of clinical toxicity secondary to recreational misuse of phenytoin in a clinical setting in India.


  Case Report Top


A 25-year-old unemployed male from a rural background attended the neurology department of a metropolitan teaching hospital. On presentation, he complained of dizziness, blurred vision, difficulty in walking, altered state of consciousness, and frequent falls, which had been sudden in onset and had persisted for the previous 4 days. On examination, he was drowsy and disoriented to time and place, was experiencing moderate ataxia, and had significant nystagmus present on lateral gaze.

A detailed history revealed that over the past 10 years, the patient had misused alcohol 500 ml/day, nicotine/2 packets per day, and cannabis three times a week and had gradually become very addicted to all these substances. In the context of a broader pattern of substance abuse, it was subsequently revealed that over the past 5 years, he had also been misusing alprazolam, pentazocine, nitrazepam, codeine, and other opioids and had no periods of abstinence longer than a few days. Patient admitted that in the past he was also abusing the substances intravenousely. But during the admission to hospital he claimed to have stopped it a few months back.

Two months prior to seeking opinion to this hospital, under the intoxication of various illicit substances he had met with a major accident. He then reduced the consumption of all substances that he had been abusing. This, however, subsequently led to three episodes of the loss of consciousness and involuntary movements of the limbs. Without disclosing his previous history of substance use, he then consulted a local doctor regarding these symptoms. An electroencephalogram did not reveal significant abnormalities, but despite this result, a provisional diagnosis of a seizure disorder was considered and he was subsequently prescribed tablet phenytoin 100 mg twice daily. He reported that after starting phenytoin, he felt better, comfortable, with a state of well-being. Consequently, his friend advised him to increase the dose by self for faster recovery and well-being. Later in the context of peer pressure, patient had gradually increased the dose of phenytoin up to 600 mg/day without medical supervision. He reported that he consumed the tablets at this dose twice daily for 15 days prior to his recent presentation to hospital.

A provisional diagnosis of polysubstance abuse with phenytoin toxicity was considered, although financial constraints precluded the measurement of the serum phenytoin concentration and the diagnosis was thus made on clinical grounds. The plan at this time was to taper the phenytoin dose to 100 mg daily. The patient was referred to the psychiatric department and was admitted for further management. In the psychiatry ward, he was cooperative, conscious, and oriented. Further examination revealed increased psychomotor activity, slurred speech, and sleep disturbance. At this time, phenytoin was ceased, and treatment with clonazepam 0.25 mg twice daily, risperidone 2 mg at night, trihexyphenidyl 2 mg at night, and pantoprazole 40 mg daily was commenced.

On day 2, of his psychiatric hospital stay, naltrexone was also started at 50 mg every night, along with a transdermal nicotine patch 7 mg/day for the next 2 weeks. He was advised to stay in hospital but after 14 days of hospital stay patient took discharge against medical advice. A month later he visited our outpatient department and reported that he had some cravings for nicotine but was able to manage the symptom with transdermal nicotine. Subsequently, he was lost to follow-up.


  Discussion Top


Substance abuse use disorders have been described as a worldwide public health crisis, largely because of adverse socioeconomic impacts and health consequences.[7] In India, a survey by the Indian Ministry of Social Justice and Empowerment found that at least 10.7 million Indian citizens are thought to be recreational drug users with 8.7 million people regularly consuming cannabis and a further 2 million people abusing opiates.[8],[9] Diagnostic criteria stipulate that if an individual uses at least three different classes of substances indiscriminately but do not have a specific predisposition to a favored drug, then it is considered to be consistent with a diagnosis of polysubstance abuse.[10]

In the case presented here, the patient was abusing alcohol, nicotine, cannabis, alprazolam, pentazocine, nitrazepam, codeine, other opioids along with phenytoin. This patient was thought to have had seizure activity following discontinuation of substance use. Withdrawal seizures are common among those who are dependent on alcohol and other drugs after discontinuation of use or substantial dose reductions. In this case, many of the substances abused (with the exception of nicotine) are reported to cause withdrawal seizures.[9],[10],[11] Withdrawal seizures typically terminate spontaneously or are easily controlled with benzodiazepines. In this case, the patient was thought to have presented with a history of withdrawal seizure activity, but due to the absence of full disclosure of medication usage history, phenytoin was introduced. As his seizure activity was probably part of drug withdrawal the use of phenytoin was questionable, as some physicians do give phenytoin for the management of alcohol withdrawal seizures.

Excessive self-medication, misunderstanding of the prescription order, and probable drug interaction are three important causes of acute phenytoin intoxication.[2],[3],[4],[5] One issue complicating this presentation is that phenytoin exhibits zero-order pharmacokinetics, and therefore, carries an increased risk of dose-related toxicity that is an important issue in emergency medicine. In this case, in the context of peer pressure, friends advised the patient to take much greater than the prescribed dose of phenytoin, and a friend working in a pharmacy facilitated access to his supply of the anticonvulsant. Phenytoin is 70% bioavailable after oral ingestion. The volume of distribution is approximately 0.5–0.8 L/kg, with significant protein binding in vivo. Metabolism follows first-order kinetics in the therapeutic range and mild overdoses, meaning that a fixed percentage of phenytoin is eliminated over a given period. At higher concentrations, the cytochrome P450 enzyme system becomes saturated, leading to zero-order kinetics in which a fixed amount of phenytoin is eliminated over a given period. This results in a prolonged half-life (24–230 h in overdose) and contributes to increased serum concentrations. Given the pharmacokinetic profile of phenytoin, a small increase in the dose can give rise to a disproportionately large increase in the serum concentration, and thus, in this case, there was substantial potential for clinical toxicity. Even in the therapeutic use of phenytoin, toxicity may occur before a steady state is reached, and it is, therefore, prudent to monitor for toxic symptoms and to consider a serum phenytoin level checkup several days (e.g., 3–5 days) after dosage initiation or adjustment.[12],[13]

Central nervous system effects, including ataxia, nystagmus, slurred speech, decreased coordination, and paradoxical seizures, are the most common presenting symptoms of phenytoin toxicity. In acute phenytoin toxicity, nystagmus is seen in 95%, ataxia in 88%, and seizures in 19% of cases.[2],[3],[4],[5] In this case he presented a range of typical symtoms of phenytoin toxicity including dizziness, blurred vision, difficulty in walking, altered state of consciousness, frequent falls, moderate ataxia, and significant nystagmus.[12],[13],[14] The management of acute phenytoin intoxication includes temporary withdrawal of phenytoin and supportive care. In this case, symptoms were markedly improved within 48 h of discontinuation of phenytoin.


  Conclusion Top


This case serves to raise awareness of the potential for the abuse/misuse of phenytoin, particularly among those with a history of polysubstance abuse. In addition, the circumstances reported here emphasize the need to obtain an accurate and comprehensive medication history when prescribing, in particular, encompassing details of possible substance misuse.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Lowry JA, Vandover JC, DeGreeff J, Scalzo AJ. Unusual presentation of iatrogenic phenytoin toxicity in a newborn. J Med Toxicol 2005;1:26-9.  Back to cited text no. 4
    
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Thakral A, Shenoy R, Deleu D. Acute visual dysfunction following phenytoin-induced toxicity. Acta Neurol Belg 2003;103:218-20.  Back to cited text no. 5
    
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Jenkins A. A case of phenytoin toxicity in a patient with advanced lung cancer. Palliat Med 2006;20:479-80.  Back to cited text no. 6
    
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Islam RN, Tabassum NE, Saifuzzaman AK, Sarker MM. A case study of drug abuse. Med Today 2012;24:82-4.  Back to cited text no. 7
    
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Chaitanya Mallapur. India's Soaring Drug Problem: 455%. Available from: https://www.archive.indiaspend.com. [Last accessed on 2017 Jun 22].  Back to cited text no. 8
    
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Murthy P, Manjunatha N, Subodh BN, Chand PK, Benegal V. Substance use and addiction research in India. Indian J Psychiatry 2010;52:S189-99.  Back to cited text no. 9
    
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Connor JP, Gullo MJ, White A, Kelly AB. Polysubstance use: Diagnostic challenges, patterns of use and health. Curr Opin Psychiatry 2014;27:269-75.  Back to cited text no. 10
    
11.
Roldan CJ. Phenytoin toxicity from cocaine adulteration. West J Emerg Med 2014;15:127-30.  Back to cited text no. 11
    
12.
Wu MF, Hing W. Phenytoin: A guide to therapeutic drug monitoring. Proc Singapore Healthc 2013;3:198-202.  Back to cited text no. 12
    
13.
Murphy JM, Motiwala R, Devinsky O. Phenytoin intoxication. South Med J 1991;84:1199-204.  Back to cited text no. 13
    
14.
Shukla A, Sankar J, Verma A, Dubey N. Acute phenytoin intoxication in a 4-year-old mimicking viral meningoencephalitis. BMJ Case Rep 2013;2013. pii: bcr2013009492.  Back to cited text no. 14
    




 

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