Journal of Forensic and Legal Medicine 34 (2015) 113e118

Contents lists available at ScienceDirect

Journal of Forensic and Legal Medicine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j fl m

Review

Forensic pharmacovigilance: Newer dimension of pharmacovigilance Rakesh K. Sewal, Vikas K. Saini, Bikash Medhi* Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

a r t i c l e i n f o

a b s t r a c t

Article history: Received 4 October 2014 Received in revised form 25 March 2015 Accepted 29 May 2015 Available online 6 June 2015

Drug safety for the patients is of paramount importance for a medical professional. Pharmacovigilance attempts to ensure the safety of patients by keeping a close vigil on the pattern of adverse events secondary to drug use. Number of medicolegal cases is at rise since last few years. Forensic sciences and pharmacovigilance need to work hand in hand to unlock the mystery of many criminal and civil proceedings. Pharmacovigilance offers its wide scope in forensic sciences by putting forward its expertise on adverse profile of drugs which may be instrumental in solving the cases and bringing the justice forth. It may range from as simple affairs as defining the adverse drug reaction on one hand to putting expert advice in critical criminal cases on the other one. Pharmacovigilance experts have to abide by the ethics of the practice while executing their duties as expert else it may tarnish the justice and loosen its dependability. As a budding discipline of science, it is confronted with several hurdles and challenges which include reluctance of medical professionals for being involved in court proceedings, extrapolations of facts and data and variations in law across the globe etc. These challenges and hurdles call the medical fraternity come forward to work towards the momentous application of pharmacovigilance in the forensic sciences. Evidence based practice e.g. testing the biological samples for the presence of drugs may prove to be pivotal in the success of this collaboration of sciences. © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Keywords: Pharmacovigilance Forensic science Medicolegal Adverse drug reaction

1. Introduction Pharmacovigilance has witnessed an exponential growth in last few decades owing to the increasing awareness amongst healthcare professionals. Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.1 The various components of pharmacovigilance ranging from detection to prevention of adverse drug reactions (ADR's) lay a strong foundation for the solution of medicolegal cases. A medicolegal case is where a person is injured or harmed in any way and needs medical attention for it. Medicolegal cases comprise of detection and collection of evidences in accidents, suicides and homicides. In this contemporary world of medicine, medicolegal issues are emerging out at an alarming rate.2 This is worthwhile to mention that law and medical professionals need to work hand in hand for the sake of betterment and rehabilitation of the victims of medicolegal cases.3 Forensic sciences and pharmacovigilance offer collaborative services to each

* Corresponding author. Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. Tel.: þ91 172 2755250 (O), þ91 9815409652 (M); fax: þ91 1722744401, þ91 1722745078. E-mail address: [email protected] (B. Medhi).

other for the benefit of stakeholders. They can exchange the knowledge with each other to complement the information. This symbiotic relationship of two vital components of healthcare system gives birth to a new discipline known as “Forensic Pharmacovigilance”. 2. Scope of pharmacovigilance in forensic medicine 2.1. Illicit drug use Illicit drug use cases seek the expert opinion on drugs and their possible adverse events. The illegal drugs use is on rise since few decades. The number of intentional and unintentional deaths from prescription drugs overdose is now greater than the deaths from heroin and cocaine combined. A large part of the problem is the use of pain-killers without a prescription, or misusing a prescribed drug to get “high.” Improving the way prescription painkillers are prescribed can reduce the number of people who misuse, abuse or overdose these drugs, while making sure patients have access to safe and effective treatment. In 2011, legislation to create a Prescription Drug Monitoring Program was passed in Maryland to make comprehensive information on prescribed and dispensed Controlled Dangerous Substances available to doctors, pharmacists and other healthcare providers.4

http://dx.doi.org/10.1016/j.jflm.2015.05.015 1752-928X/© 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

114

R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118

2.2. Role in solving civil or criminal cases During the criminal proceedings, involvement of drugs in a case may seek the expert advice of pharmacovigilance to solve the case.5 Examples of such cases include death due to overdose toxicity of drugs like sedatives being used for sleep disorders or opiates used for pain management. Under few circumstances, apart from the involvement of toxicological effects of drugs; there are certain adverse drug reactions which can be attributed responsible for occurrence of the legal case. The fact that suicidal tendencies secondary to the use of antidepressants are the known adverse effects of these drugs may be useful in mining/unleashing the cause of

death of a person treated by these drugs and who commits a suicide leaving a mystery behind.6 Table 1 enlists the examples of drugs and their forensic significance which illustrates the relevance of drugs’ knowledge in forensic concerns. 2.3. Differentiation between adverse drug reaction and adverse event Any untoward medical occurrence that may appear during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with the treatment is called

Table 1 Examples of drugs explain their possible ADR's of forensic significance. S. No.

Drug

Class/Use

ADR

Forensic significance

Reference

1

Citalopram

QTc interval prolongation

May cause adverse drug reactions of serious outcomes

7,8

2 3

Dextropropoxyphene Flunitrazepam

QTc interval prolongation QTc interval prolongation

May cause adverse drug reactions of serious outcomes May cause adverse drug reactions of serious outcomes

9e11

4

Methadone

Selective serotonin reuptake inhibitors Opioid analgesic Intermediate acting benzodiazepine Opioid analgesic

Respiratory arrest

13,14

5

Varenicline Digoxin

7 8 9 10

Fentanyl Heroin Cefuroxime Morphine

Opioid analgesic Opiate Cephalosporin Opioid analgesic

11

Aldicarb

12

Trazodone Atracurium

While mining the evidences in death of such cases suicidal ideation may be considered. Overdose toxicity for Suicidal intention

25,26

13 14 15

Cyclizine Zopiclone

Overdose toxicity may result in death Suicidal attempt results in fatality

28,29

16

Fluoxetine

Acetylcholinestearse inhibitor Antidepressant, anxiolytic, and hypnotic Nondepolarizing skeletal muscle relaxant Antihistaminic Nonbenzodiazepine hypnotic agent Selective serotonin reuptake inhibitor

Death involving a suspicion of suicide committed by a person taking varenicline ST depression,Ventricular fibrillation leading to fatal or other serious outcome Overdose toxicity may result in death. Cardiac failure which may be an explanation of death Unexpected death Intentional or accidental overdose results in death. Medication error or suicidal events should be differentiated. Death due to an aldicarb acute intoxication.

15,16

6

Nicotinic acetylcholine receptor agonist Cardiac glycoside

QT Prolongation Respiratory depression Manic episodes induced Suicidal Ideation Arrhythmia

Suicidal ideation information may be instrumental in solving mysterious death cases

31

17

Imipramine

17

18 19

Mephedrone Quinidine

20

Clozapine

21 22

Thioridazine Dextromethorphan

Atypical antidepressant Antipsychotic Antitussive

Complete atrio-ventricular heart block resulting in sudden death Impaired judgement may cause accidental death Rapid ventricular arrhythmia results in death. Reason of death may be explained. Myocarditis induced death due to overdose Arrhythmogenic sudden cardiac death Death from respiratory failure

35

23 24

Acetamenophen Ceftriaxone

NSAID/Antipyretic Cephalosporin

37

25 26

Tetracycline Thyroxine

27

Azathioprine

Antibiotic Congenital hypothyroidism Immunosuppresant

Fulminant hepatic failure Hemolytic anemia induced cardio-respiratory arrest, Acute renal failure Hepatotoxicity Cardiac Arrest Serious pancytopenia due to the accumulation of cytotoxic metabolites

42e44

28 29

Doxorubicin Rifampicin/Isoniazide/ Ethambutol/Pyrazinamide Enalapril Propofol

Cardiomyopathy or cardiac failure Acute liver failure due to hepatic encephalopathy

45,46

Hepatic failure Death occurred due to pulmonary oedema as patient did not receive ventilation

41

30 31

Tricyclic antidepressant CNS stimulant Anti arrhythmic

Cytotoxic Antitubercular FDC ACE inhibitor Anaesthetic

Respiratory depression Mast cell degradation Disulfiram-like reaction Respiratory depression leading to death in severe cases CNS depression Suicidal ideation Hypertension and tachycardia and hypotension and bradycardia CNS depression, hypertension Amnesia, palpitation, hallucination Development of akathisia related to the development of suicidal ideation. Depresses automaticity Delirium QT prolongation Myocarditis Arrhythmia Tachycardia, hypertension, and respiratory depression Hepatotoxicity Auto eimmune hemolytic anemia Jaundice Progressive bradycardia Bone marrow suppression, hematological toxicity, pancreatitis Cardiotoxicity Hepatotoxicity Hepatotoxicity Pulmonary oedema and haemorrhagic pancreatitis, respiratory depression, bronchospasm and chest wall rigidity

12

17

18 19,20 21 22

23,24

27

30

32 17

33,34

36

38,39

40 41

47

48

R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118

as adverse event. According to WHO, adverse drug reaction is defined as “A response to a drug which is noxious and unintended; and occurs at doses normally used in man for the prophylaxis; diagnosis or therapy of disease, or for modification of physiological function.49 Thus, every adverse drug reaction is an adverse event but not vice versa. Keeping this point in view, it is pertinent to cautiously identify these two aspects of unintended experiences after the use of drugs. “Causality assessment” is the tool to put scientific evidence forth to determine the accurate nature of adverse experience after a drug use. If there is any stronger or weaker correlation of administration of drug with the occurrence of adverse event then it is known as adverse drug reaction. There are several causality assessment scales adopted by the pharmacovigilance experts to assign the level of correlation. Naranjos's scale, WHO's causality assessment scale and Bayesian scale are few to name.50,51 Different degrees of association are described by these scales e.g. certain, probable, possible and unlikely are the levels mentioned by the WHO's scale for causality assessment.52,53 2.4. Discrimination between serious and severe ADR's There is a thin line of demarcation between serious and severe drug reactions which are misunderstood many a times. Court proceedings may be in a need to judge the gravity of problem in terms of seriousness and severity. Severe reactions should never be confused with serious reactions. For instance, in any drug related injury in clinical trials compensation is granted to the victim for which judiciary needs to ascertain whether the injury was serious or not. There is a criterion almost universally accepted for determining the seriousness of drug reaction. If the ADR falls in to the bracket of that criterion then it should be designated as serious event. A reaction is said to be serious if it 1) results in death, 2) is lifethreatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) results in congenital abnormality, and 6) is any other medically important condition. Severity of the ADR's deals with the intensity of the reaction graded as mild, moderate, severe.49 Severe is never synonymous with serious e.g. headache may be severe in grade but not of great medical significance for seriousness.

115

2.5. Identification of counterfeit and substandard drugs Pharmacovigilance data can generate the signal for some specific drug and/or its formulations; under some instances. Forensic pharmacovigilance is useful when counterfeit or substandard drugs cause the adverse events. Standard pharmacovigilance methods of registration, analysis and investigation are able in indentifying the substandard drugs or formulations which have caused the adverse events. Thousands of adverse reactions in USA which are secondary to administration of contaminated heparin in 2009 is an example of adverse events occurred due to contaminated or counterfeit drugs which generates the signal for taking corrective action as it happened in case of the present example. Market authorization holder had to recall all heparin due to alarming figure of ADR's including hundreds of fatalities.54 Few areas of scope of forensic pharmacovigilance are depicted in Fig. 1.

3. Forensic pharmacovigilance as another bud of pharmacovigilance Though birth of pharmacovigilance owes back to the occurrence of a disaster known popularly as thalidomide tragedy but it has attained a proliferative growth in last few decades.55 Pharmacovigilance has gained a pace to expand its applications in other streams of science. Ecopharmacovigilance, which is defined as science and activities concerning detection, assessment, understanding, and prevention of adverse effects or other problems related to the presence of pharmaceuticals in the environment, which affect human and other animal species is a recent development of pharmacovigilance proving its relevance in environmental sciences.56 Haemovigilance, materiovigilance, biovigilance are few more examples which are transformed facet of pharmacovigilance. For example, in Indian context, haemovigilance is covered under pharmacovigilance program of India as blood or blood products are governed by drug regulatory authorities in India treating them as a drug.57 On the same pattern we have recently seen a newer budding branch of pharmacovigilance i.e Forensic Pharmacovigilance which is instrumental in solving the legal issues raised on involvement of any drug. Forensic pharmacovigilance i.e

Fig. 1. Scope of forensic pharmacovigilance.

116

R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118

implementation of pharmacovigilance expertise for forensic purpose may be used to answer the following questions: Could the drug under question (or chemical) have caused the adverse effect in the victim ? Did it cause the effect either ‘beyond all reasonable doubt?’ (criminal case) or ‘as a balance of probabilities (civil case)?3 4. Challenges and hurdles in forensic pharmacovigilance 4.1. Reluctance of medical professionals Reluctance of medical professionals in playing their role as an expert for forensic purposes is one of the sturdiest challenges to be met. Causes contributing to the medical professional's reluctance include fear of litigation, loss of productivity, fear of being twisted by lawyers etc.58 Despite of these challenges medical professionals should undertake the civic duties by contributing their expertise in resolving the forensic issues. 4.2. Extrapolation of a data does not always produce the real figures Extrapolation of data generated through previous studies or experiences cannot always be practised. Competitiveness and quality of epidemiological studies in medicine always lies under question mark making it difficult to accept their conclusion for making decisions in some forensic issues.59 4.3. Uniformity vs non uniformity Medical Sciences have similar foundation across the globe but law varies across the borders. Medical profession is not open to public rather it depends upon the subjective opinion of the professionals whereas in contrast law is open at mass levels and has a strong foundation of defined rules. Though in forensic pharmacovigilance both the disciplines need to work hand in hand but there are certain conflictions. Medicine discipline is challenged by the law often during the trials. 4.4. Ethics in forensic pharmacovigilance Judiciary has to rely more upon the opinion of the expert in a case involving the drug. They rely more upon the testimony of forensic experts. Therefore, an ethical obligation always lies upon expert to put the truth forward and not to mislead the judiciary, defense, or the state when testifying before the court, or when preparing their reports relating to their analyses of forensic evidence. We still lack any universally applicable guidelines on ethical code for the forensic sciences. Though there are few professional bodies catering to the needs of forensic analysts on ethics in forensic sciences. American Board of Criminalistics (ABC) and the American Academy of Forensic Science are two professional bodies useful for forensic scientists in United States of America.60 In a study conducted by Brandon L. Garrett and Peter J. Neufeld in 2009 six types of invalid testimony could be identified which are enlisted as below.61 ▪ Evidence that was non-probative presented as probative ▪ Discounting exculpatory evidence ▪ Conclusion of evidence originating from the defendant without supporting empirical data ▪ Non-statistical statements made without supporting empirical data ▪ Inaccurate presentation of statistics or frequency ▪ Providing statistics without supporting empirical data

An expert needs to be unbiased and fair enough in his/her obligations. The prime obligation of an expert must be to contribute towards the justice. Legal, scientific, and ethical values can become snarled during the court proceedings. It becomes a responsibility of an expert to keep his opinion after a competent, unbiased and probative work. The causes behind practising unethical acts include avarice, zeal of power or over ambitions of promotion, status or personal welfare. Sometimes even casual behaviour of experts towards professional duties also makes their acts unethical. Living with guilt of that a guilty person escapes and or an impeccant person gets punished based on the advice or comments submitted by the pharmacovigilance expert may restrain him or her from unethical acts. Professional bodies and organizations should put the efforts forward to ensure ethical practice, veracity of testimony among individuals engaged as expert for forensic purpose. It is pertinent to devise a code of conduct for such professionals to keep the benchmark of ethics in forensic sciences. 5. Key points for an effective forensic pharmacovigilance 5.1. Forensic pharmacokinetics Forensic pharmacokinetics should be honoured while giving the opinion or report on medico legal case involving the drugs. If possible, biological samples should be collected to assess them for the presence of drugs or their metabolites which further can be correlated with the adverse events related to the forensic concerns. Claims of adverse drug reactions may be supported by data of pharmacokinetics.2 Pharmacokinetics/Pharmacodynamics (PK/PD) studies are gaining the popularity at various levels of research which may be a tool for the effective implementation of pharmacovigilance in forensic sciences. 5.2. Temporal relationship Temporal relationship of occurrence of adverse event and administration of drug should be taken into consideration while preparing the report for forensic purposes. The time lag between administration of drug and occurrence of ADR defines the time course of a reaction which is of six types:      

Rapid: toxic reactions First-dose: hypersensitivity reactions Early: collateral reactions Intermediate ecollateral or hyper sensitivity reactions Late ecollateral reactions Delayed ecollateral reactions62

Temporal relationship lays a strong foundation for the causality assessment of the case and also plays a vital role for the judgement purposes e.g. immediate reactions showing a close temporal relationship-between the adverse event and administration of dose makes judiciary more convinced. Sometimes, when a far temporal association lies between the administration of drug and event and there is any scientific fact explaining that gap, an advice of experts in pharmacovigilance or pharmacology must be sought because there are certain drugs which causes the adverse events only after accumulation of the drug or its metabolite in the body e.g. morphine. But, there are certain exceptions in classification cited here e.g. hypersensitivity reaction is usually immediate reactions but may be delayed in few instances. Stevens Johnson Syndrome secondary to paracetamol after chronic use may be an example of such delayed immune mediated reaction.

R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118

5.3. Causality assessment of the case Causality assessment determines the degree of probability of correlation of administration of a drug and occurrence of adverse event. It must be exercised cautiously and tested rigorously before putting a report before the bench of a court. Several scales are being used for causality assessment like Naranjo's scale, WHO's Scale for causality assessment and Probability algorithm. A pharmacovigilance expert should cautiously use the scale of causality assessment and it should be specified in the report submitted to the judiciary.52 5.4. Cautious extrapolation of facts to every case Exaggerated extrapolation of the case to some fact or data may tarnish the proceedings of the forensic cases. It may entirely mislead the verdict of the criminal or civil cases. Cautious extrapolation is warranted to avoid such misleading judgements based upon inaccurate data. 5.5. Challenges of pharmacovigilance Though pharmacovigilance is set to offer its application in forensic sciences but there are few challenges before the pharmacovigilance to be met. Increased globalization of drugs, exponential rise in volume of drugs used and polypharmacy are few elements which make the pharmacovigilance a complex discipline. Under the light of these challenges, pharmacovigilance now should be understood beyond merely reporting the harms; rather it should be a rigorous risk benefit assessment. Few standards of quality in pharmacovigilance have been set and good pharmacovigilance practices (GVP) is a citable example of that.63 It is imperative to adhere to such standards while implementing pharmacovigilance in forensic areas. 5.6. Presenting evidence for the court Proper presentation of the evidences by the medical or pharmacovigilance expert may illuminate the case. A report for the forensic purposes should be written clearly and should not include the comments from the area which is beyond the expertise who is submitting the report. A clear statement should be made in report if some additional advice of another expert is needed. Scientifics evidences, facts and observation should be presented in a manner that can easily be understood by judges to make them arrive at a verdict with reasonably fair understanding of the case.58 6. Conclusions In the light of increasing medicolegal cases, there is a substantial need of contribution of drug expertise in solving the criminal and civil cases involving the drugs at one or other stages. Pharmacovigilance is the science of detection, assessment, understanding, prevention of adverse events associated with the use of drugs. Pharmacovigilance can cater to the needs of legal framework to mine the cases involving the drugs by differentiating the serious and non serious reactions, establishing the causal relationship between drug and adverse event. Proliferating role of pharmacovigilance has now sprawled over the arena of legal medicine giving birth to newer branch of science known as forensic pharmacovigilance which offers a wide range of its scope and application and warrants a cautious execution of this exercise else it may deviate from the intended use. Conflict of interest None declared.

117

Funding None declared. Ethical approval None declared. References 1. World Health Organization Collaborating Centre for International Drug Monitoring. The importance of pharmacovigilance safety monitoring of medicinal products. Geneva: World Health Organization; 2002. 2. Medhi B, Singh PK, Bansal YS, Setia P. Forensic pharmacokinetics: a new dimension for drug related medico legal cases. J Forensic Res 2011;2:128. http:// dx.doi.org/10.4172/2157-7145.1000128. 3. Edwards IR, Body D. Forensic pharmacovigilance. Int J Risk Saf Med 2012;12: 241e2. 4. Drug induced deaths. Maryland: Department of Mental Health and Hygiene; 2012. 5. Aronson JK, Hauben M. Anecdotes that provide definitive evidence. BMJ 2006;333:1267e9. 6. Kielholz P, Battegay R. Behandlung depressiver Zustandsbilder, unter spezieller Berücksichtigung von Tofranil, einem neuen Antidepressivum. Schweiz Med Wochenschr 1958;88:763e7. 7. Catalano G, Catalano MC, Epstein MA, Tsambiras PE. QTc interval prolongation associated with citalopram overdose: a case report and literature review. Clin Neuropharmacol 2001;24(3):158e62. 8. Jonasson B, Saldeen T. Citalopram in fatal poisoning cases. Forensic Sci Int 2002;126(1):1e6. 9. Carson DJL, Carson ED. Fatal dextropropoxyphene poisoning in Northern Ireland: review of 30 cases. Lancet 1977;309(8017):894e7. 10. Lawson AAH, Northridge DB. Dextropropoxyphene overdose. Med Toxicol Adverse Drug Exp 1987;2(6):430e44. 11. Hawton K, Simkin S, Deeks J. Co-proxamol and suicide: a study of national mortality statistics and local non-fatal self poisonings. BMJ 2003;326(7397): 1006. 12. Barnett JM, Broad RM. Flunitrazepam used in a case of poisoning. J Clin Forensic Med 2003;10(2):89e91. 13. Modesto-Lowe V, Brooks D, Petry N. Methadone deaths: risk factors in pain and addicted populations. J Gen Intern Med 2010;25(4):305e9. 14. Andrews CM, Krantz MJ, Wedam EF, Marcuson MJ, Capacchione JF, Haigney MC. Methadone-induced mortality in the treatment of chronic pain: role of QT prolongation. Cardiol J 2009;16(3):210e7. 15. Kintz P, Evans J, Villain M, Cirimele V. Smoking cessation with varenicline: a suicidal fatality. J Anal Toxicol 2009;33(2):118e20. 16. Stove CP, Els A, Piette MH, Lambert WE. Fatality following a suicidal overdose with varenicline. Int J Leg Med 2013;127(1):85e91. 17. Bigger JT, Weld FM. Drugs and sudden cardiac death. Ann N Y Acad Sci 1982;382(1):229e37. 18. Algren DA, Monteilh CP, Punja M, Schier JG, Belson M, Hepler BR, et al. Fentanyl-associated fatalities among illicit drug users in Wayne county, Michigan (July 2005eMay 2006). J Med Toxicol 2013;9(1):106e15. 19. Edston E, Hage-Hamsten MV, Edston E. Anaphylactoid shockea common cause of death in heroin addicts? Allergy 1997;52(9):950e4. 20. Darke S, Zador D. Fatal heroin ‘overdose’: a review. Addiction 1996;91(12): 1765e72. 21. Dong H, Zhang J, Ren L, Liu Q, Zhu S. Unexpected death due to cefuroximeinduced disulfiram-like reaction. Indian J Pharmacol 2013;45(4):399. 22. Centers for Disease Control and Prevention. CDC grand rounds: prescription drug overdoses-a US epidemic. Morb Mortal Wkly Rep 2012;61(1):10. 23. Proença P, Teixeira H, de Mendonca MC, Castanheira F, Marques EP, CorteReal F, et al. Aldicarb poisoning: one case report. Forensic Sci Int 2004;146: S79e81. 24. Ragouc-Sengler C, Tracqui A, Chavonnet A, Daijardin JB, Simonetti M, Kintz P, et al. Aldicarb poisoning. Hum Exp Toxicol 2000;19(12):657e62. 25. Martínez MA, Ballesteros S, de la Torre CS, Almarza E. Investigation of a fatality due to trazodone poisoning: case report and literature review. J Anal Toxicol 2005;29(4):262e8. 26. Gamble DE, Peterson LG. Trazodone overdose: four years of experience from voluntary reports. J Clin Psychiatry 1986;47(11):544e6. 27. Martínez MA, Ballesteros S, Almarza E. Anesthesiologist suicide with atracurium. J Anal Toxicol 2006;30(2):120. 28. Arnestad M, Eldor KBB, Stray-Pedersen A, Bachs L, Karinen R. Suicide due to cyclizine overdose. J Anal Toxicol 2014;38:110e2. 29. Backer RC, McFeeley P, Wohlenberg N. Fatality resulting from cyclizine overdose. J Anal Toxicol 1989;13(5):308e9. 30. Meatherall RC. Zopiclone fatality in a hospitalized patient. J Forensic Sci 1997;42(2):340e3. 31. Creaney W, Murray I, Healy D. Antidepressant induced suicidal ideation. J Psychopharmacol 1992;6(1):120. 32. Corkery JM, Schifano F, Ghodse AH. Mephedrone-related fatalities in the United Kingdom: contextual, clinical and practical issues. Pharmacology 2012;17: 355e80.

118

R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118

33. De Berardis D, Serroni N, Campanella D, Olivieri L, Ferri F, Carano A, et al. Update on the adverse effects of clozapine: focus on myocarditis. Curr Drug Saf 2012;7(1):55e62. 34. Fineschi V, Ner M, Riezzo I, Turillazzi E. Sudden cardiac death due to hypersensitivity myocarditis during clozapine treatment. Int J Leg Med 2004;118(5): 307e9. 35. Killeen DMJ. Antipsychotic-induced sudden cardiac death: examination of an atypical reaction. Expert Opin Drug Saf 2009;8(3):249e52. 36. Burns JM, Boyer EW. Antitussives and substance abuse. Subst Abuse Rehabilitation 2013;4:75e82. http://dx.doi.org/10.2147/SAR.S36761. 37. McCormick PA, Treanor D, McCormack G. Farrell M. Early death from paracetamol (acetaminophen) induced fulminant hepatic failure without cerebral oedema. J Hepatol 2003;39(4):547e51. 38. Garratty G, Postoway N, Schwellenbach J, McMahill PC. A fatal case of ceftriaxone (Rocephin)-induced hemolytic anaemia associated with intravascular immune hemolysis. Transfusion 1991;31:176e9. 39. Kapur G, Valentini RP, Mattoo TK, Warrier I, Imam AA. Ceftriaxone induced hemolysis complicated by acute renal failure. Pediatr Blood Cancer 2008;50(1): 139e42. 40. Hanson GC. A death from tetracycline. Postgrad Med J 1968;44:870e4. http:// dx.doi.org/10.1136/pgmj.44.517.870. 41. Cheng K, Masters S, Stephenson T, Cooke R, Ferner R, Ashworth M, et al. Identification of suspected fatal adverse drug reactions by paediatricians: a UK surveillance study. Arch Dis Child 2008;93:609e11. 42. Breen DP, Marinaki AM, Arenas M, Hayes PC. Pharmacogeneticassociation with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation. Liver Transpl 2005;11(7):826e33. 43. Andersen V, Sonne J, Andersen M. Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999. Eur J ClinPharmacol 2001;57(6e7):517e21. 44. Gastal GR, Moreira S, Noble CF, Ferreira LE, França PH, Pinho M. Toxicity of azathioprine: why and when: analysis of the prevalence of polymorphism in Joinville, SC, Brazil. Arq Gastroenterol 2012;49(2):130e4. 45. Clarkson A, Choonara I. Surveillance for fatal suspected adverse drug reactions in the UK. Arch Dis Child 2002;87:462e7. 46. Ichikawa Y, Ghanefar M, Bayeva1 M, Wu R, Khechaduri A, Sathyamangla V, et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest 2014;124(2):617e30.

47. Tost JR, Vidal R, Cayla J, Díaz-Cabanela D, Jimenez A, Broquetas JM. Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis 2005;9(5):534e40. 48. Roussin A, Mirepoix M, Lassabe G, Dumestre-Toulet V, Gardette V, Montastruc JL, et al. Death related to a recreational abuse of propofol at therapeutic dose range. Br J Anaesth 2006;97(2):268. 49. [Internet] Glossary of terms used in pharmacovigilance. 2011 March [cited 2014 Feb 22]. Available from:, http://who-umc.org/Graphics/24729.pdf. 50. Agbabiaka TB, Savovic J, Ernst E. Methods for causality assessment of adverse drug reactions a systematic review. Drug Saf 2008;31(1):21e37. 51. Edwards IR. Considerations on causality in pharmacovigilance. Int J Risk Saf Med 2012:2441e54. http://dx.doi.org/10.3233/JRS-2012-0552. 52. Zaki SA. Adverse drug reaction and causality assessment scales. Lung India 2011;28:152e3. 53. [Internet] The use of the WHO-UMC system for standardised case causality assessment. 2012 April 17 [cited 2014 Mar27]. Available from:, http://whoumc.org/Graphics/24734.pdf. 54. Labadie J. Forensic pharmacovigilance and substandard or counterfeit drugs. Int J Risk Saf Med 2012;24:2437e9. 55. Grootheest KV. The dawn of Pharmacovigilance: an historical prospective. Int J Pharm Med 2003;17:195e200. 56. Medhi B, Sewal RK. Ecopharmacovigilance: an issue urgently to be addressed. Indian J Pharmacol 2012;44(5):547e9. 57. Bisht A, Singh S, Marwah N. Hemovigilance Programme-India. Asian J Transfus Sci 2013;7:73e4. 58. Hartigan-Go Kenneth. Presenting evidence for the court. Int J Risk Saf Med 2012;24:59e63. 59. Persaud N, Healy D. Epidemiological evidence in forensic pharmacovigilance. Int J Risk Saf Med 2012;24:31e5. 60. Dutelle AW. Ethics and forensic science. Mar-Apr Evid Technol Mag 2011;9(2): 24e5. 61. Barnett Peter D. Ethics in forensic science: professional standards for the practice of criminalistics. Boca Raton, FL: CRC Press; 2001. 62. Aronson JK, Ferner RE. Clarification of terminology in drug safety. Drug Saf 2005;28(10):851e70. 63. Jeetu G, Anusha G. Pharmacovigilance: a worldwide master key for drug safety monitoring. J Young Pharm 2010;2(3):315e20.

Forensic pharmacovigilance: Newer dimension of pharmacovigilance.

Drug safety for the patients is of paramount importance for a medical professional. Pharmacovigilance attempts to ensure the safety of patients by kee...
454KB Sizes 1 Downloads 9 Views