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) What is idiosyncratic reaction example?These are classified as nonimmuno-mediated idiosyncratic reactions (Kaplowitz, 2001). Examples of drugs that are known to cause this type of idiosyncratic reaction include troglitazone, valproate, amiodarone, ketoconazole, disulfiram, and isoniazid.
What causes idiosyncratic drug reactions?The proposed mechanism of most idiosyncratic drug reactions is immune-mediated toxicity. To create an immune response, a foreign molecule must be present that antibodies can bind to (i.e. the antigen) and cellular damage must exist.
What are often associated with idiosyncratic reactions?The anticonvulsants carbamazepine and phenytoin are associated with idiosyncratic drug reactions, where these reactions include fever, neutropenia, and skin rash (including Stevens-Johnson syndrome) (219).
What is idiosyncratic drug toxicity?Idiosyncratic toxicity can occur when a convergence of risk factors, including drug exposure, tips the risk-benefit balance away from benefit and toward risk.
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