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. Even though this appears in the syllabus, it is extremely unlikely for this specific definition to ever appear in the written exam, considering its relative unimportance. Rather than the definition, the recognition and management of these syndromes is probably the more relevant matter. Show
In terms of peer-reviewed resources dealing with this topic, Goodman & Gillman (12th ed) probably has the best all-round definition of idiosyncrasy on page 76 of the 12th edition. (around page 1.49). The Textbook of Pharmacology by Seth has a competing definition (around page 1.49). Those definitions are approximately one paragraph, which is probably enough for the pragmatic exam candidate. If for whatever reason a substantial depth of knowledge is called for, the article by Uetrecht & Naisbitt (2013) would be the single best resource. In summary:
Pharmacological definition of idiosyncrasyThe definition from Textbook of Pharmacology by Seth is:
That's probably as good as it gets. 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". These authors decided to describe it as
That is quite different from Goodman & Gillman:
This definition is probably the most suitable because it is short and generic. It also allows for an idiosyncratic lack of a reaction, i.e an individual who is uniquely insensitive to a substance. 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. The ability to define this term is probably quite irrelevant from the perspective of actually practising intensive care medicine. The more interesting elements would probably be the causes, consequences and management of idiopathic drug reactions. Pathophysiology of idiosyncratic drug reactionsIdiosyncratic reactions are generally thought to be immune-mediated. There is no agreement on their precise mechanism, and there are many exceptions to contradict every hypothesis. In summary:
Virtually every idiosyncratic response has a distinct syndrome of symptoms and organ dysfunction, but some shared characteristics do exist.
Classical examples of drug-induced idiosyncratic reactionsThere is the distinct possibility that some cruel viva scenario will call for the sweating exam candidate to produce a list of idiosyncratic drug reactions as examples. A solid offering from the literature is hard to find. Here is a short list which was generated by combing through the article by Knowles et al (2000) and Park et al (1992) Idiosyncratic Drug Reaction Syndromes
ReferencesWhat is an unexpected response to a drug that is peculiar to the individual?An adverse drug reaction (ADR) includes allergic reactions (immunologic hypersensitivity, the result of unusual sensitivity to a drug) and idiosyncratic reactions (abnormal susceptibility to a drug that is peculiar to the individual).
What is idiosyncratic reaction of a drug?The term idiosyncratic drug reaction (IDR) has been used in various ways and has no clear definition, but the term is used in this review to designate an adverse reaction that does not occur in most patients treated with a drug and does not involve the therapeutic effect of the drug.
What is an example of an idiosyncratic reaction?Some idiosyncratic reactions appear to be caused by a direct cytotoxic effect of the drug or its metabolites, without pathogenetic involvement of the immune system (Ju and Uetrecht, 2002). As far as AEDs are concerned, the best example of such reactions is probably VPA-induced hepatotoxicity.
Which term means an unexpected reaction to a drug?Adverse drug reactions (ADRs) – unintended, harmful events attributed to the use of medicines – occur as a cause of and during a significant proportion of unscheduled hospital admissions.
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