ERA’S JOURNAL OF MEDICAL RESEARCHVOL.2 NO.1
DRUG IDIOSYNCRASY IN OPHTHALMIC PRACTICE
Rajendra Kr. Bundela
B. B. Lal
Department of Ophthalmology
Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh India– 226003.
Address for correspondence
Idiosyncratic drug reactions, denoting non–immunological
Dr. Rajendra Kr. Bundela
hypersensitivity to a substance, have been a neglected entity. The
idiosyncrasy, more often than not, is confused with hypersensitivity,
Department of Ophthalmology
which is an undesirable reaction of normal immune system. The present
Era's Lucknow Medical College and
article gives an insight of the various aspects of idiosyncrasy and
idiosyncratic responses of drugs commonly used in ophthalmic practice.
Tel. No. +91–9336344412,
Key words: Idiosyncrasy, Hypersensitivity, Hypersensitivity,
is qualitatively similar in all individuals, but the
Drug idiosyncrasy in ophthalmic practice, being
idiosyncratic response may take the form of extreme
uncommon or better said being under–emphasized, has
sensitivity to low doses or extreme insensitivity to high
been a neglected entity. The term idiosyncratic drug
doses of chemicals. These genetic polymorphisms can
reaction means different things to different people, but in
be due to inter–individual differences in drug
this perspective, it will be used to indicate an adverse
pharmacokinetics, such as phase I and phase II
drug reaction that does not occur in most patients at any
biotransformation enzymes. The polymorphisms also
readily achieved dose of a drug and does not involve the
can be due to pharmacodynamic factors such as drug–
known pharmacologic effects of the drug. Once the
receptor interactions (2).
idiosyncrasy is diagnosed, the only best approach is to
withdraw the drug to avoid any idiosyncratic response
Idiosyncratic drug reactions are type B reactions, which
going wild. It is important to know about the entity and
occur rarely and unpredictably amongst the population.
also the commonly used drugs in ophthalmic practice
They frequently occur with exposure to new drugs, as
known to show idiosyncrasy.
they have not been fully tested and full range of
possible side–effects have not been discovered. This is
Idiosyncrasy deﬁned the way physicians conceived
not to be mistaken with idiopathic which implies that
diseases in the nineteenth century. They considered each
the cause is not known (3).
disease as a unique condition, related to each patient.
This understanding began to change in the 1870s. In
Idiosyncratic drug reaction does not appear to be
contemporary medicine (as of 2007) the term
Idiosyncratic Drug Reaction' denotes a non–
concentration dependent. A minimal amount of drug
immunological hypersensitivity to a substance, without
will cause an immune response, but it is suspected that
connection to pharmacological toxicity. Idiosyncrasy
at a low enough concentration, a drug will be less likely
stresses here the fact that other individuals would react
to initiate an immune response. The dose of a drug to
differently, or not at all and that the reaction is an
produce the same effect may vary by 4–6 folds among
individual one, based on a speciﬁc condition of the one
different individuals. This is mainly because of
who suffers from it (1).
differing rates of drug metabolism as the amount of
microsomal enzymes is genetically controlled. There
Idiosyncrasy is deﬁned as a genetically determined
are also differences in target organ sensitivity. A
abnormal reactivity to chemicals. The observed response
continuous variation with Gaussian frequency
18 ERA’S JOURNAL OF MEDICAL RESEARCHJan.–June.2015VOL.2 NO.1
Most commonly, this is caused by enzymopathy,
distribution is seen in the case of most drugs. However,
congenital or acquired, so that the triggering substance
there are some speciﬁc genetic defects which lead to
cannot be processed properly in the organism and
discontinuous variation in drug responses (4), e.g;
causes symptoms by accumulating or blocking other
substances to be processed(1). Enzymopathy–comprise
1. Atypical pseudo cholinesterase
a large class of genetic diseases involving disorder of
2. G–6–PD deﬁciency
metabolism. The majority are due to defects of single
3. Acetylator polymorphism
gene that codes for enzymes which facilitate
4. Acute intermittent porphyria
conversion of various substances into other products,
5. CYP2D6 abnormality
resulting either in accumulation of substance or
6. Precipitation of an attack of angle closure glaucoma
reduced ability to synthesize sensational compounds
by mydiatrics in individuals with narrow
Idiosyncrasy response should not be confused with
MECHANISM OF IDIOSYNCRASY
hypersensitivity reactions which refer to undesirable
In adverse drug reactions involving overdose, the toxic
reactions produced by normal immune system.
effects is simply an extension of the pharmacological
Hypersensitivity requires a pre–sensitized (immune)
effect (Type A of adverse drug reactions), on the other
state of the host. Various forms of hypersensitivity
hand, clinical symptoms of idiosyncratic drug reactions
reactions have been recognized in humans which are
(Type B adverse drug reactions) are different from the
often referred as allergies; collectively.
pharmacological effect of the drug.
An Idiosyncrasy causing symptoms like allergy is also
The proposed mechanism of cellular damage in case of
called pseudoanaphylaxis and its presentation is similar
idiosyncratic drug reactions are immune mediated
to that of anaphylaxis. It however does not involve an
toxicity either from toxic drug/drug metabolite or it may
allergic reaction but is due to direct mast cell
come from an injury or infection. To create an immune
response, you must have a foreign molecule that
antibodies combine to (i.e. the antigen) and you must
There is no clinical difference between allergy and
have cellular damage. Very often, drug will not be
idiosyncrasy, both can be self–limiting. Broadly
immunogenic because they are too small to bind to
Idiosyncrasy is treated symptomatically and its general
antibodies, however a drug can cause a immune response
prophylaxis includes a good family history of patient,
if the drug binds a larger molecule. The second criteria of
as it may suggest strong hypersensitivity to a particular
cellular damage can come either from a toxic drug/drug
drug. Mode of delivery of a drug should be properly
metabolite or it may come from an injury/ infection.
checked, as the drug, when used systemically may
These will sensitize the immune system to the drug and
cause idiosyncrasy but not when used topically or vice–
cause a response (3).
Table 1: Differences between Idiosyncrasy and Hypersensitivity
Type B adverse drug reaction Type A adverse drug reaction
Direct mast cell degranulation Reactions require a pre–sensitized immune state of the host
Uncharacteristic or Bizarre drug effect Stereotype symptoms which are unrelated to pharmacodynamic
due to peculiarities of an individuals proﬁle of drug
Genetically determined abnormal An Immunological mediated
reactivity to chemical reaction
19 DRUG IDIOSYNCRASY IN OPHTHALMIC PRACTICE
Table 1: Differences between Idiosyncrasy and Hypersensitivity
Extreme sensitivity to low doses or Independent of dosage
extreme insensitivity to high doses
Genetic polymorphisms can be due No genetic predisposition as well as
to inter–individual differences in no role of drug pharmacokinetics
Table:2 Drugs commonly used in ophthalmic practice causing idiosyncrasy
Drugs Idiosyncratic Manifestations
Sulpha group Conjunctival chemosis, corneal epithelial
(a)– Sulfonamide(7–9) edema, Acute periocular edema, acute hemolysis.
(b)– Acetazolamide (10) Drowsiness
Atropine (11) Periocular pufﬁness, Dermatitis,
Homatropine(11) Same as Atropine
Phenylephrine(12) Lid retraction, Photosensitivity
Chloramphenicol(13) Optic neuritis , Acute hemolysis
(aplastic anaemia), Digital paresthesias
Mild mercuric Chloride(14) Irritative conjunctivitis
Yellow mercuric oxide(14) Irritative conjunctivitis
Iodine(15) Periocular pigmentation, conjunctival irritation.
CONCLUSION AND FUTURE PROSPECTS
RNA interference is an area of intense, upfront basic research and holds the key to various technological applications
in future due to their higher silencing efﬁciency and shorter time requirements for screening and to analyses functions
of wide variety of genes in different organisms. The RNA silencing technology apart from being highly sequence
speciﬁc is also technologically facile and economical. Therefore, this technique has great potential in agriculture
speciﬁcally for nutritional improvement of plants and the management of various plant diseases. Future directions
will focus on developing ﬁnely tuned RNAi–based gene silencing vectors that are able to operate in a temporally and
spatially controlled manner. In coming years better and comprehensive understanding of RNAi would allow the
researchers to work effectively and efﬁciently in order to work more on improvement of crop plants nutritionally and
in managing various diseases of crop plants. Finally, the discovery of RNAi has not only provided us with a powerful
new experimental tool to study the function of genes but also raises expectations about future applications of RNAi in
20 ERA’S JOURNAL OF MEDICAL RESEARCHJan.–June.2015VOL.2 NO.1
reactions to sulphonamides and sulfonamide–
CONFLICT OF INTEREST
trimethoprin antimicrobrials: clinical syndromes and
The authors declare that they have no competing interests.
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