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.
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:
- Idiosyncrasy is an abnormal reactivity to a chemical that is peculiar to a given individual. 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
Pharmacological definition of idiosyncrasy
The definition from Textbook of Pharmacology by Seth is:
"an unusual response or a highly exaggerated usual response to usual doses to some drugs in few individuals"
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
"an adverse reaction that does not occur in most patients treated with a drug and does not involve the therapeutic effect of the drug".
That is quite different from Goodman & Gillman:
"Idiosyncrasy is an abnormal reactivity to a chemical that is peculiar to a given individual"
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 reactions
Idiosyncratic 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:
- 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
Virtually every idiosyncratic response has a distinct syndrome of symptoms and organ dysfunction, but some shared characteristics do exist.
- Multi-organ involvement is very common
- 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 skin rash is almost always involved
- They will frequently resolve in spite of continuing treatment with the offending drug because of the development of tolerance.
Classical examples of drug-induced idiosyncratic reactions
There 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)
| Syndrome | Drugs | Features |
| Stevens-Johnson syndrome and toxic epidermal necrolysis |
|
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| Serum sickness-like reaction |
| |
| Drug-induced lupus |
|
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| Drug-induced hepatitis |
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| Aplastic anaemia, agranulocytosis |
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Medically Reviewed by Carol DerSarkissian, MD on February 08, 2022
A placebo is anything that seems to be a "real" medical treatment -- but isn't. It could be a pill, a shot, or some other type of "fake" treatment. What all placebos have in common is that they do not contain an active substance meant to affect health. Researchers use placebos during studies to help them understand what effect a new drug or some other treatment might have on a particular condition. For instance, some people in a study might be given a new drug to lower cholesterol. Others would get a placebo. None of the people in the study will know if they got the real treatment or the placebo. Researchers then compare the effects of the drug and the placebo on the people in the study. That way, they can determine the effectiveness of the new drug and check for side effects. Sometimes a person can have a response to a placebo. The response can be positive or negative. For instance, the person's symptoms may improve. Or the person may have what appears to be side effects from the treatment. These responses are known as the "placebo effect." There are some conditions in which a placebo can produce results even when people know they are taking a placebo. Studies show that placebos can have an effect on conditions such as: In one study involving asthma, people using a placebo inhaler did no better on breathing tests than sitting and doing nothing. But when researchers asked for people's perception of how they felt, the placebo inhaler was reported as being as effective as medicine in providing relief. Research on the placebo effect has focused on the relationship of mind and body. One of the most common theories is that the placebo effect is due to a person's expectations. If a person expects a pill to do something, then it's possible that the body's own chemistry can cause effects similar to what a medication might have caused.
For instance, in one study, people were given a placebo and told it was a stimulant. After taking the pill, their pulse rate sped up, their blood pressure increased, and their reaction speeds improved. When people were given the same pill and told it was to help them get to sleep, they experienced the opposite effects. Experts also say that there is a relationship between how strongly a person expects to have results and whether or not results occur. The stronger the feeling, the more likely it is that a person will experience positive effects. There may be a profound effect due to the interaction between a patient and healthcare provider. The same appears to be true for negative effects. If people expect to have side effects such as headaches, nausea, or drowsiness, there is a greater chance of those reactions happening. The fact that the placebo effect is tied to expectations doesn't make it imaginary or fake. Some studies show that there are actual physical changes that occur with the placebo effect. For instance, some studies have documented an increase in the body's production of endorphins, one of the body's natural pain relievers. One problem with the placebo effect is that it can be difficult to distinguish from the actual effects of a real drug during a study. Finding ways to distinguish between the placebo effect and the effect of treatment may help improve the treatment and lower the cost of drug testing. And more study may also lead to ways to use the power of the placebo effect in treating disease.