idiosyncratic reactions ppt
More recently, a lower estimate of severe liver injury of 1:1000 has been given for isoniazid from a large tuberculosis public health clinic, as 11 of 11 141 patients developed isoniazid-induced liver disease. Oxidative pathway yields trifluoroacetylchloride, which can react with microsomal proteins to form a neoantigen which then can generate immune response leading to hepatic injury. Adverse drug reactions (ADRâs) are defined the effects created by drugs producing unintended or noxious response. Idiosyncratic drug reactions are unpredictable reactions that can result in significant morbidity and mortality. It could be: An abnormally exaggerated response, or an abnormal lack of response, A response unusual because it requires an unusually small or unusually large dose, An extension of the normal physiological drug effect, A reaction which is unrelated to the expected physiological effect, Idiosyncrasy is not a drug allergy, but both are forms of adverse drug reaction, Idiosyncratic drug reactions are unrelated to the dose of the drug, Common lifethreatening idiosyncratic drug reactions include DRESS syndrome, toxic epidermal necrolysis and Stevens-Johnson syndrome, Either the drug itself, or a reactive metabolite, binds to a protein, That protein undergoes a chemical and morphological change, breaking self-tolerance, The immune system reacts to this altered protein in a multitude of ways, which usually resemble an adaptive immune response but can also feature eosinophilia, There is usually a (long) delay between starting the drug and the onset of symptoms, Risk of an idiosyncratic reaction does not seem to increase with dose. A minimal amount of drug will cause an immune response, but it is suspected that at a low enough concentration, a drug will be less likely to initiate an immune response. The major targets are skin, liver, and bone marrow. There is mild to severe bridging hepatocyte degeneration and necrosis with evidence of apoptosis. The immune system is very complex, and it will not be easy to gain a thorough mechanistic understanding of IDRs. Many idiosyncratic drug reactions are believed to be immune mediated. Postulated mechanism of immune-mediated halothane hepatotoxicity. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. Our current mechanistic understanding of IDRs is superficial and a subject of significant debate. It could be an abnormally exaggerated response, or an abnormal lack of response, or an abnormal extension of the normal physiological drug effect, or a reaction which is completely unrelated to the expected physiological effect. In summary: Virtually every idiosyncratic response has a distinct syndrome of symptoms and organ dysfunction, but some shared characteristics do exist. A few IDRs have a strong HLA association, but with the exception of abacavir hypersensitivity, most patients with the required HLA will not have an IDR when treated with the relevant drug. ", "Idiosyncratic drug reactions: current understanding. Mild to moderate periportal inflammation is reported. Neoantigens may result from adducts formed from the interaction of reactive drug metabolites with cellular proteins. WikiMatrix. TYPES OF REACTIONS PPT SCI 10.ppt â PowerPoint presentation, 1751 kB (1793536 bytes) Document Actions. "Idiosyncratic drug reactions: the reactive metabolite syndromes. Indeed in the majority of cases, no true allergy testing ever occurs. Although valid animal models are essential for controlled experiments, any model must be linked to IDRs in humans to make sure that it is relevant. Meaning of idiosyncratic reaction. Chemical reactions presentation. Carprofen is a non-steroidal anti-inflammatory agent. The hepatic effect appears to be associated with metabolism by hepatic flavin monooxygenase to a reactive N-methylthiourea metabolite. Various drugs are believed to cause immune-mediated idiosyncratic reactions in humans, including halothane, diclofenac, phenytoin, and sulfonamides (Sturgill and Lambert, 1997; Watkins, 1999; Zimmerman, 1999; Treinen-Moslen, 2001). Affected dogs have elevated alanine transaminase, aspartate transaminase, alkaline phosphates and serum total bilirubin. This specific risk, also called unsystematic, can be nulled out of a portfolio through diversification. Atrayee Banerjee, in Handbook of Toxicology of Chemical Warfare Agents (Third Edition), 2020. Find PowerPoint Presentations and Slides using the power of XPowerPoint.com, find free presentations research about Toxicity Idiosyncratic PPT [International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use.] Mechanistic studies are very difficult to perform and little is known with certainty about their mechanisms. springer. Idiosyncratic risk is the risk inherent in an asset or asset group, due to specific qualities of that asset. 4. March 11, 2020. With a better mechanistic understanding of IDRs, it should be possible to better predict which drugs are likely to cause such adverse reactions and to treat serious IDRs to prevent death and serious sequelae. Most of these signals turn out to be false-positives, but investigation of these signals further delays drug approval, which significantly adds to the cost of drug development. The major targets are skin, liver, and bone marrow. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. kellers1. They'll give your presentations a professional, memorable appearance - the kind of sophisticated look that today's audiences expect. For dose-dependent hepatotoxins, the diagnosis may be easier to establish than for idiosyncratic drug reactions. Noun. By continuing you agree to the use of cookies. Idiosyncratic risk is the risk inherent in an asset or asset group, due to specific qualities of that asset. What is Idiosyncratic Risk? Design a Free Chemistry Powerpoint Template and Google Slides Themes which can help you a lot in your Educational or Science/Chemistry slides Project work. The major targets are skin, liver, and bone marrow. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. A solid offering from the literature is hard to find. Therefore it is better to refer to these adverse effects as contrast media hypersensitivity reactions 6. The clinical presentation in cats is similar to that described with carprofen in dogs. Apica, W.M. This latency between initiation of therapy and the onset of liver disease is a component of the signature of reactions to specific drugs and provides some clues to the pathogenesis. Type A are predictable, dose-related toxicities, often id ⦠Although these reactions are commonly called contrast allergies or allergic reactions, the use of the word allergy is unhelpful as the majority of the reactions are not immune-mediated, and therefore not true allergic reactions. We use cookies to help provide and enhance our service and tailor content and ads. Therefore, solving the issue of IDRs would greatly facilitate drug development, as well as improve drug safety. In lay terms, when we say someone has a certain idiosyncrasy, we refer to a habit or mannerism that's peculiar to that person. A classic Recently, zonisamide has been reported to cause acute liver failure after 10â20 days of dosing (Trepanier, 2013; Weingarten and Sande, 2015). Idiosyncratic reactions are qualitatively aberrant reactions that cannot be explained by the known phar-macologic action of the drug and occur only in a small percent of the population. From: Clinical Trials (Second Edition), 2016, A. Mak, J. Uetrecht, in Comprehensive Toxicology (Third Edition), 2018. Methimazole is another example of agents causing idiosyncratic hepatotoxicosis affecting humans and cats. of idiosyncratic reactions can be minimized by knowledge of risk factors, avoidance of specific AEDs in subpopulations at risk, cautious dose titration, and careful monitoring of clini-cal response. It occurs in 1 in 1000 to 1 in 50 000 individuals who take the drug. There is no agreement on their precise mechanism, and there are many exceptions to contradict every hypothesis. These are classified as nonimmuno-mediated idiosyncratic reactions (Kaplowitz, 2001). Also known as Type B Reactions/ Bizarre Reactions These occur rarely and unpredictably amongst the population. The principle of heterologous immunity implies that there need not be structural similarity between the pathogen and the drug-modified protein in order for the pathogen to shape the immune response so that it responds strongly to an immunogen produced by the drug. If for whatever reason a substantial depth of knowledge is called for, the article by Uetrecht & Naisbitt (2013) would be the single best resource. ADVERTISEMENT. Idiosyncratic drug reactions, also known as type B reactions, are drug reactions that occur rarely and unpredictably amongst the population. Hepatotoxic adverse drug reactions are associated with significant morbidity and mortality and are the leading cause of postmarketing regulatory action in the United States. These guidelines outline the steps an experienced clinician might use to assess the likelihood of a drug reaction. Liver injury can be a result of both direct cytotoxicity and antibody-dependent cellular toxicity. This chapter is directly related to Section D(ii) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "define... idiosyncrasy..." along with several other related terms. Adverse drug reactions. Clinical signs of idiosyncratic reaction to carprofen occur 20 days on average following the first exposure to the drug and include anorexia, vomiting, and icterus. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. Key Words: Antiepileptic drugsâAdverse drug reactionsâIdiosyncratic effectsâToxicityâReview. ", Stevens-Johnson syndrome and toxic epidermal necrolysis. Idiosyncrasy is an abnormal reactivity to a chemical that is peculiar to a given individual. Toxicol. 1999, 12, 5, 387-395. The Textbook of Pharmacology by Seth has a competing definition (around page 1.49). Toxicol. 5 months ago. It is impossible to give a clear official definition for exam purposes because the term, as Uetrecht and Nasibitt put it, "has been used in various ways and has no clear definition". Knowles, Sandra R., Jack Uetrecht, and Neil H. Shear. Severe idiosyncratic drug reactions are often characterised by fever and internal organ involvement. There are other terms â such as common share, ordinary share, or voting share â that are equivalent to common stock. IDRs represent a significant source of patient morbidity and mortality, and they also significantly increase the risk of drug development. (around page 1.49). Jack Uetrecht, in Drug-Induced Liver Disease (Third Edition), 2013. idiosyncratic reaction ( plural idiosyncratic reactions ) ( pharmacy, medicine) A reaction to a medication that is unusual and unpredictable, specific to a particular person. Idiosyncratic drug reactions account for the majority of hepatotoxicity associated with drugs worldwide. However, most patients do not have the same degree of impaired immune tolerance as these animal models. Rev. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. "Idiosyncratic adverse drug reactions: current concepts." Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. Idiosyncratic reactions to sulfonamides occur in about 0.25% of dogs and a variety of organ systems are affected, hepatopathy being the third most reported sequela. Patients usually present with icterus. A delay of 3â4 weeks after 1â2 weeks course of medication (e.g., amoxicillin-clavulanic acid) occurs before clinical signs become evident (Kaplowitz, 2001; Zimmerman, 1999), but onset is expedited with rechallenge (Dahm and Jones, 1996; Sturgill and Lambert, 1997; Watkins, 1999). Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. Causality assessment factors typically include the temporal relationship, course after cessation of the drug, risk factors, concomitant drugs, a search for nondrug causes (viral hepatitis), previous information concerning the drug, and response to rechallenge, which is typically not required. Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The differential diagnosis of toxin- and drug-induced liver injury includes almost the entire spectrum of liver diseases. Using this definition, adverse reactions, such as cardiac arrhythmias caused by drugs that affect potassium channels, would not be idiosyncratic because they involve known pharmacological properties of the drug. It opens the possibility that the reaction is an extension of the therapeutic effect of the drug (unlike Uetrecht & Nasibitt) and it does not restrict it to reactions resulting from "usual" doses, allowing for situations where a laughably small or comically large dose of the drug produces the unexpected effect. 65 sentence examples: 1. In that sense, it is deliberately idiosyncratic. Idiosyncratic reactions occur in small numbers, so some drugs continue to be used when their usefulness or uniqueness makes the risk acceptable. Mild to moderate periportal inflammation is reported. Download Hi-Res Image Download to MS-PowerPoint Cite This: Chem. Similar drugs exhibit similar features called âclass effectsâ, Individual drugs in a class still vary considerably, Reactions occur at varying time intervals after ingestion (3 days to 1 year), Reactions vary in severity, but typically severe and fatal if drug continued, Mild injury often disappears with continued use (adaptation), Rarity of most reactions suggests possibility of multiple hits, Rechallenge is virtually always met with greater severity, shorter latency. Idiosyncrasy is an abnormal reactivity to a chemical that is peculiar to a given individual. Idiosyncratic drug reactions, also known as type B reactions, are drug reactions that occur rarely and unpredictably amongst the population. I- Addition Reactions ⦠Common Stock Common stock is a type of security that represents ownership of equity in a company. Meaning of idiosyncratic reaction. Definition of idiosyncratic reaction in the Definitions.net dictionary. Various drugs are believed to cause immune-mediated idiosyncratic reactions in humans, including halothane, diclofenac, phenytoin, and sulfonamides (Sturgill and Lambert, 1997; Watkins, 1999; Zimmerman, 1999; Treinen-Moslen, 2001). Find all the evidence you need on "Idiosyncratic drug reaction" via the Trip Database. Many idiosyncratic drug reactions are believed to be immune-mediated. A minimal amount of drug will cause an immune response, but it is suspected that at a low enough concentration, a drug will be less likely to initiate an immune response. Acetaldehyde, produced by metabolism of ethanol, forms adducts with hepatic proteins similar to halothane, resulting in higher antibody titers to which some of the liver damage following ethanol ingestion may be attributed (Ramaiah et al., 2004). Types of Organic Reactions AGUNG RAHMADANI DEPARTMENT OF PHARMACY UNIVERSITY OF MULAWARMAN SAMARINDA 2014. categories of organic reactions There are so many types of organic reactions. Severe idiosyncratic drug reactions are often characterised by fever and internal organ involvement. The ability to define this term is probably quite irrelevant from the perspective of actually practising intensive care medicine. These neoantigens may be processed by Kupffer cells or other antigen-presenting cells, transported to the cell surface, and presented as antigens. These reactions are called idiosyncratic. The types of adverse reaction can be studies in two main headings, i.e., more common ADRs including type A and. Liver transplantation (Chapter 157) is performed in more than 50% of patients with idiosyncratic drug-induced acute liver failure because the survival rate in this setting without transplantation is less than 20%. However, the role of immune-mediated liver damage following ethanol ingestion is minimal compared to other known mechanisms of alcohol liver damage. Res. There is mild to severe bridging degeneration and necrosis with evidence of apoptosis. Apart from isoniazid, antibiotics, nonsteroidals, and anticonvulsants are the most commonly associated drug class capable of inducing idiosyncratic reactions. That begs the question of what determines who will develop an IDR to a specific drug. Diclofenac generates reactive metabolites and forms a hapten (Trepanier, 2013). In adverse drug reactions involving overdoses, the toxic effect is simply an extension of the pharmacological effect. When your doctor prescribes a medication, neither you or the doctor expect it to be a life-threatening drug, but sometimes it is just that. This will be difficult to accomplish without a much better mechanistic understanding of IDILI and other IDRs. B All chemical reactions need a certain amount of activation energy to get started. Lee, in Pathobiology of Human Disease, 2014. adverse drug reaction (ADR), "a response to a drug which is noxious and unintended and which occurs at doses normally used in man [sic] for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function." Example sentences with "idiosyncratic reactions", translation memory. Other idiosyncratic reactions of veterinary importance include diazepam in cats (Center et al., 1996) and sulfonamides in dogs (Trepanier et al., 2003; Shenton et al., 2004; Trepanier, 2004). Idiosyncratic drug reactions, also known as type B reactions, are drug reactions that occur rarely and unpredictably amongst the population. Although the major working hypothesis for the mechanism of idiosyncratic drug reactions (IDRs), the hapten hypothesis, has not changed since 1987, several hypotheses have been added, for example, the danger hypothesis and the pharmaceutical interaction hypothesis. Information and translations of idiosyncratic reaction in the most comprehensive dictionary definitions resource on the web. Alcoholic liver disease is another example of possible immune-mediated damage. Whether it is an organic or inorganic reaction, it can be explained with free Chemistry PPT backgrounds. Because the clinical picture of drug-induced liver injury ranges from pure hepatocellular to pure cholestatic variants, a high index of suspicion must be maintained, even when toxin- or drug-induced liver injury is not obvious initially. Giga-fren. An example is the individual with infectious mononucleosis who develops a ⦠Cell and antibody-mediated immune responses can cause severe liver damage. Part of the mechanism of injury due to diclofenac in humans could be due to mitochondrial injury (Trepanier, 2013). Addition Reactions Substitution Reactions Elimination Reactions Oxidation Reduction Reaction. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. Adverse drug events, adverse drug reactions. What does idiosyncratic reaction mean? The risk can be managed by having a diversified investment portfolio. Print this. These agents can also cause IDRs similar to small molecules, and in many cases, the IDR was not predicted based on the target of the drug. Idiosyncratic reactions are generally thought to be immune-mediated. Idiosyncratic drug reactions (IDRs) are adverse drug reactions that are not related to the known pharmacological properties of the drug occur in only a small percentage of the population and do not show any apparent doseâresponse relationship. Here is a short list which was generated by combing through the article by Knowles et al (2000) and Park et al (1992), Previous chapter: Addiction, dependence and withdrawal, Next chapter: Variability of response to anaesthetic agents. 5. Clinical signs of the idiosyncratic reaction to carprofen, an NSAID, in dogs include anorexia, vomiting, and icterus and occur approximately 20 days following the first exposure to the drug. Many drugs implicated in idiosyncratic liver injury are known to affect mitochondrial function (Stirnimann et al., 2010). Antibiotics and anticonvulsants are highly associated with drug-induced liver disease, whereas hormones, antihypertensive drugs, digoxin, and antiarrhythmic drugs (some exceptions) are very rarely associated with liver injury. In their review of hypersensitivity and idiosyncratic reactions to oxaliplatin, Thomas et al. In their review of hypersensitivity and idiosyncratic reactions to oxaliplatin, Thomas et al. Brayne also held idiosyncratic views on the hereafter. The delay in onset is consistent with an immune mechanism because it takes time for lymphocytes to recognize a specific immunogen to expand to sufficient numbers to produce a clinically evident response. Affected dogs have elevated ALT, AST, ALP, and serum total bilirubin. The energy required to break the bonds in the reactants for a chemical reaction to occur. 4. Idiosyncrasy is an abnormal reactivity to a chemical that is peculiar to a given individual. Various drugs believed to cause immune-mediated idiosyncratic reactions in humans include halothane, diclofenac, phenytoin, and sulfonamides (Sturgill and Lambert, 1997; Watkins, 1999; Zimmerman, 1999; Treinen-Moslen, 2001). Those definitions are approximately one paragraph, which is probably enough for the pragmatic exam candidate. It occurs in 1 in 1000 to 1 in 50 000 individuals who take the drug. Activation Energy. There are three principal hypotheses for how reactive metabolites might i ⦠Idiosyncratic infusion related reactions # % of patients treated with Replagal in clinical trials have experienced idiosyncratic infusion related reactions Giga-fren If reactive metabolites are responsible for most idiosyncratic reactions due to health products, it should be possible to prevent such reactions by avoiding reactive metabolites. Idiosyncratic drug reaction occurs in very few individuals exposed to drugs that are known to be hepatotoxic. 1 concluded that patients who develop severe hypersensitivity reactions (HSRs) to oxaliplatin are unlikely to tolerate further therapy. This is still a high rate of injury compared to other idiosyncratic drug reactions, yet the usefulness of the drug has precluded its withdrawal. This suggests that factors leading to activation of the immune system would increase the risk of IDRs, but with few exceptions, multiple lines of evidence suggest that this is not the case. Some dampen the immune response to treat immune-mediated diseases and others are designed to stimulate the immune system or impair immune tolerance to treat cancer. 3D Business Chemistry Education Science. This definition is probably the most suitable because it is short and generic. Adverse drug events: a perspective. The proportion of drug-induced liver disease varies greatly among drug classes as evidence of class effect. Idiosyncratic reactions are qualitatively aberrant reactions that cannot be explained by the known phar-macologic action of the drug and occur only in a small percent of the population. These neoantigens are processed by Kupffer cells or other antigen presenting cells, transported to the cell surface, and presented to the immune system. Cell- and antibody-mediated immune response may cause severe liver damage. Pharmacological reviews65.2 (2013): 779-808. The risk can be managed by having a diversified investment portfolio. Such late idiosyncratic reactions are usually quite serious. Hepatotoxic adverse drug reactions are associated with significant morbidity and mortality and are the leading cause of postmarketing regulatory action in the United States. Copyright © 2021 Elsevier B.V. or its licensors or contributors. Features of idiosyncrasy suggest a role for the innate and adaptive immune response systems (Table 1). The evidence to date suggests that most, but not all, IDRs are caused by reactive metabolites and are immune mediated. Free 3d Atom PowerPoint Template. A few idiosyncratic drug reactions have been reported in veterinary medicine. 1 concluded that patients who develop severe hypersensitivity reactions (HSRs) to oxaliplatin are unlikely to tolerate further therapy. report. Hepatopathy is the third most reported reaction to sulfonamides and other effects may include polyarthropathy, which may predominate in Doberman pinchers, thrombocytopenia, pyrexia, and dermal drug eruptions (Trepanier, 2004). Although the major working hypothesis for the mechanism of idiosyncratic drug reactions (IDRs), the hapten hypothesis, has not changed since 1987, several hypotheses have been added, for example, the danger hypothesis and the pharmaceutical interaction hypothesis. Download free Chemistry Powerpoint templates to gain excel grade in your project work. arthralgias, Ranges from asymptomatic LFT derangement to fulminant liver failure, Can be selective (eg. The major targets are skin, liver, and bone marrow. Catastrophic pulmonary vasoconstriction, an idiosyncratic reaction to protamine, occurred following cardiopulmonary bypass in a patient with mitral regurgitation. Idiosyncratic definition, pertaining to the nature of idiosyncrasy, or something peculiar to an individual: The best minds are idiosyncratic and unpredictable as they follow the course of ⦠Idiosyncratic DILI typically occurs 1â3 months after initiation of a drug but varies among drugs and patients. Oxidative pathway yields trifluoroacetylchloride, which can react with microsomal proteins to form a neoantigen which then can generate immune response leading to hepatic injury. Signs do not correlate with drug dose. Idiosyncratic Adverse Drug Reactions. Idiosyncratic reactions to contrast agents start usually within 20 minutes after injection and occur more frequently in patients 20 to 40 years old. Karyn Bischoff, Shashi K. Ramaiah, in Veterinary Toxicology, 2007. Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. Although acute liver failure is rare, 13-17% of all acute liver failure cases are attributed to idiosyncratic drug reactions. This idiosyncratic reaction to carprofen is most likely similar to that of diclofenac in humans. Signs do not correlate with drug dose. Idiosyncratic reactions to a given drug occur at a higher frequency in patients with a history of similar reactions to other medications, particularly structurally related compounds. Halothane-mediated hepatitis is the best example for immune-mediated liver damage. How do you know a reaction has happened? His teaching methods are idiosyncratic but successful. Well, an idiosyncratic react⦠4.5. dcattanach. Pharmacol. Neoantigens may result from adducts formed from the interaction of reactive drug metabolites with cellular proteins. Types of adverse drug reactions (abcde). This adds significantly to the cost and uncertainty of drug development for several reasons: a significant effort is made to screen candidates for their potential to cause IDRs, but such efforts are mostly unsuccessful. GSH depletion is believed to play a role in human cases (Trepanier, 2013). Prompt discontinuation of a suspected drug is mandatory. Idiosyncratic drug reactions occur when sensitization is followed by reexposure to a drug, classified as immunemediated idiosyncratic hepatotoxicity (Dahm and Jones, 1996; Sturgill and Lambert, 1997; Zimmerman, 1999; Treinen-Moslen, 2001). Annu. On the other hand, clinical symptoms of Idiosyncratic drug reactions are different than the pharmacological effect of the drug. Many idiosyncratic drug reactions are believed to be immune-mediated. Uetrecht, Jack, and Dean J. Naisbitt. 3 years ago. Idiosyncratic drug reactions. These free downloadable Chemistry PPT backgrounds are fully customizable with easy-to-edit theme color as well as text. World's Best PowerPoint Templates - CrystalGraphics offers more PowerPoint templates than anyone else in the world, with over 4 million to choose from. Available antidotes should be used for acetaminophen (N-acetylcysteine) and Amanita poisoning (penicillin 300,000 to 1 million U/kg/day intravenously and thioctic acid 5 to 100 mg every 6 hours intravenously have been recommended, but there are no controlled trials). In addition, IDILI is a major problem for drug development because it is a major cause of withdrawal of drugs from the market [2]. Idiosyncratic drug reactions account for the majority of hepatotoxicity associated with drugs worldwide. An elevated bilirubin level more than twice the upper limit of normal in patients with hepatocellular liver injury implies severe DILI, with a mortality of approximately 10% and with an incidence rate of 0.7-1.3 per 100,000. Figure 15.6. These neoantigens may be processed by Kupffer cells or other antigen presenting cells, transported to the cell surface, and presented as antigens (Reynold and Moslen 1980).