IDIOSYNCRATIC REACTIONS (pharmacology)

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IDIOSYNCRATIC REACTIONS
SYNONYMS:
Hypersensitivity drug reactions; type B reactions; allergic drug reactions
DEFINITION:
Idiosyncratic drug reactions are
“adverse drug reactions that do not occur in most patients at any dose and do
not involve the known pharmacological properties of the drug”.
 A genetic or acquired abnormality in a particular metabolic pathway.
 The reactions are typically associated with a drug concentration and
often respond to simply lowering the dose of the drug.
 The idiosyncratic response may take the form of extreme sensitivity to
low doses or extreme insensitivity to high doses of chemicals.
 Certain idiosyncratic reactions can result from genetic polymorphisms
that cause individual differences in drug pharmacokinetics
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 drugs such as chlorpromazine and clozapine cause
infrequent reactions such as rhabdomyolysis (breakdown of striated
muscle) and liver toxicity.
2. A drug that caused life-threatening, idiosyncratic reactions in patients is
troglitazone. Mild, reversible hepatotoxicity from this antidiabetic drug
appeared in premarketing clinical trials in <2% of patients.
3. Only few doses of Carbamazepine may cause ataxia in some people.
 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 patients and can also cause
severe liver toxicity.
5. In some persons, barbiturates produce excitement rather than depression,
and the patient may appear to be inebriated. This type of idiosyncrasy is

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relatively common among geriatric and debilitated patients and occurs
most frequently with phenobarbital and N-methylbarbiturates.
 Barbiturates may cause restlessness, excitement, and even
delirium when given in the presence of pain and may worsen a
patient’s perception of pain.
6. One tablet of Chloroquine may cause vomiting and abdominal pain.
7. Many black males (about 10%) develop a serious hemolytic anemia when
they receive primaquine as an antimalarial therapy. Such individuals have
a deficiency of erythrocyte glucose-6-phosphate dehydrogenase.
8. Procainamide can induce autoantibodies that cause thrombocytopenia.
9. An increased incidence of peripheral neuropathy is seen in patients with
inherited deficiencies in acetylation when isoniazid is used to treat
tuberculosis.
 Isoniazid can also cause pure red cell aplasia in which there is a
decrease in the production of red cells.
10. Genetically determined resistance to the anticoagulant action of
warfarin is due to an alteration in the vitamin K epoxide reductase.


REFERENCES:
i. Encyclopedic Reference of Genomics and Proteomics in Molecular
Medicine (https://link.springer.com/referencework/10.1007/3-540-
29623-9)
ii. Goodman & Gilman's The Pharmacological Basis of Therapeutics.
(http://files.pdf-ebooks.download/pdf-ebooks.download-kupd-306.pdf)
iii. Lippincott Illustrated Reviews, Pharmacology - Whalen, Karen.
iv. http://www.authorstream.com/Presentation/SANGPB-2602204-drug-
idiosyncrasy/



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