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IDIOSYNCRATIC REACTIONS
SYNONYMS:
Hypersensitivity drugreactions; typeB reactions; allergic drugreactions
DEFINITION:
Idiosyncraticdrugreactions are
“adverse drug reactionsthat do not occur inmost patientsat any dose and do
not involve the known pharmacological propertiesof the drug”.
 A genetic or acquired abnormality in a particular metabolic pathway.
 The reactions are typically associated with a drugconcentration and
often respond to simply loweringthe doseof the drug.
 The idiosyncratic responsemay take the form of extreme sensitivity to
low dosesor extreme insensitivity to high dosesof chemicals.
 Certain idiosyncraticreactions can result from genetic polymorphisms
that cause individualdifferencesin drugpharmacokinetics
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.
EXAMPLES:
1. Antipsychotic drugssuchas chlorpromazine and clozapine cause
infrequentreactions such as rhabdomyolysis(breakdown of striated
muscle) and liver toxicity.
2. A drugthat caused life-threatening, idiosyncratic reactions in patients is
troglitazone. Mild, reversiblehepatotoxicity from this antidiabetic drug
appeared in premarketingclinical trials in <2% of patients.
3. Only few dosesof Carbamazepine may cause ataxia in somepeople.
 All antiepilepsy medications have been associated with
multiorgan hypersensitivity reactions, a rare idiosyncratic
reaction characterized by rash, fever, and systemic organ
involvement.
4. Nevirapine causes skin rash in 8-16% of patientsand can also cause
severe liver toxicity.
5. In somepersons, barbiturates produceexcitement rather than depression,
and the patient may appear to be inebriated. This type of idiosyncrasy is

2. [AuthorName]
relatively common amonggeriatric and debilitated patients and occurs
most frequently with phenobarbital and N-methylbarbiturates.
 Barbiturates may cause restlessness, excitement, and even
delirium when given in the presenceof pain and may worsen a
patient’s perception of pain.
6. One tablet of Chloroquine may cause vomitingand abdominalpain.
7. Many black males (about 10%)develop aserious hemolytic anemiawhen
they receive primaquine as an antimalarial therapy. Such individualshave
a deficiency of erythrocyte glucose-6-phosphatedehydrogenase.
8. Procainamide can induceautoantibodies that cause thrombocytopenia.
9. An increased incidenceof peripheralneuropathy isseen in patients with
inherited deficiencies in acetylation when isoniazid is used to treat
tuberculosis.
 Isoniazidcan also cause purered cell aplasia in which there is a
decrease in the production of red cells.
10. Genetically determined resistanceto the anticoagulantaction of
warfarinis dueto an alteration in the vitamin K epoxidereductase.
REFERENCES:
i. EncyclopedicReference of Genomics and Proteomics in Molecular
Medicine(https://link.springer.com/referencework/10.1007/3-540-
29623-9)
ii. Goodman & Gilman'sThe Pharmacological Basis of Therapeutics.
(http://files.pdf-ebooks.download/pdf-ebooks.download-kupd-306.pdf)
iii. LippincottIllustrated Reviews, Pharmacology - Whalen, Karen.
iv. http://www.authorstream.com/Presentation/SANGPB-2602204-drug-
idiosyncrasy/
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