Drug idiosyncrasy

DRUG
IDIOSYNCRASY
Dr.Nafeeya
Department of Forensic Medicine & Toxicology

Categories
Classification
idiosyncrasy
Monitoring & Detection
Reporting
Prevention
Forensic aspects
Overview

Categories
 Side effects
 Secondary effects
 Toxic effects
 Intolerance
 Idiosyncrasy
 Drug allergy
 Photosensitivity
 Drug dependence
 Drug withdrawal reactions
 Teratogenicity
 Mutagenicity and Carcinogenicity
 Drug induced diseases (Iatrogenic disorders)
Iatrogenic,
Idiosyncrasy,
Idiopathic,
Intolerance

Classification of Adverse Drug Reactions
● Depending upon-
● Type of reaction:
• Type A
• Type B
• Type C
• Type D
• Type E
• Type F
Onset of event:
Acute (<60 minutes)
 Sub-acute (1-24 hrs)
Latent (>2 days)
Severity:
Minor,
Moderate,
Severe,
Lethal ADRs.

Types of Adverse Drug Reactions
• Augmented(dose related)
• Bizarre (Non-Dose Related)
• Chronic (Dose Related and Time Related)
• Delayed (Time Related)
• End of Use (Withdrawal)
• Failure (Unexpected Failure of Therapy)

Bizzare (Non-Dose Related)
● Features
• Uncommon
• Not related to the pharmacologic action of the
drug
• Unpredictable
• High mortality
● Example
• Immunologic reactions: anaphylaxis to penicillin
• Idiosyncratic reactions: malignant hyperthermia
with general anesthetics
Management
•Withhold and avoid in future
I
d
o
s
y
n
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r
a
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y

Classification of ADRs-Depending on Severity
•Minor ADRs: No therapy, antidote or prolongation of
hospitalization is required.
• Moderate ADRs: Requires change in drug therapy, specific
treatment or prolongs hospital stay by atleast 1 day.
• Severe ADRs: Potentially life threatening, causes permanent
damage or requires intensive medical treatment.
• Lethal: Directly or indirectly contributes to death of the patient.

Drug idiosyncrasy" refers
to untold reactions to drugs
that occur in a small
fraction of patients and
have no obvious
relationship to dose or
duration of therapy.
Definition

DRUG IDIOSYNCRAZY
● It is genetically determined abnormal response to a drug.
● The drug interacts with some unique feature of the individual,
not found in majority of subjects, and produces the
uncharacteristic reaction.
Example :-
● Chloramphenicol produces non dose-related serious aplastic
anaemia in rare individuals.
● Barbiturates cause excitement and mental confusion in some
individuals.
● Quinine causes cramps ,asthma ,diarrhoea, vascular collapse.
● Primaquine causes acute haemolytic anaemia.

Idiosyncratic drug reaction-Causes
● Genetic abnormality
● Deficiency of enzyme in the body
● Abnormal receptor activity
● Drug interaction with unique features

Genetic abnormality
The occurrence of an
idiosyncratic reactions is
dependent on the
interaction between
multiple genes
and environmental factors

Common Pharmacogenetics Polymorphism

Deficiency of enzyme in the body
● Pseudocholinesterase deficiency
● Glucose 6 phosphate dehydrogenase deficiency
Succinylcholine or Mivacurium
Quinine, aspirin ,NSAID, sulfa drugs,

Abnormal receptor activity
● Activated receptors directly or indirectly regulate cell. Receptors
are macromolecules involved in chemical signaling between
chemical processes .
1. Ligand gated ion channel
2. G-protein coupled receptor
3. Enzyme linked
4. Nuclear receptors

Drug interaction with unique features
● Mechanism :
1. Pharmaceutical interaction
2. Pharmacokinetics interaction
3. Pharmacodynamics interaction

Alcohol idiosyncratic reaction
unusual condition that occurs when a small amount of alcohol
produces intoxication that results in
• Aggression,
• Impaired consciousness,
• Prolonged sleep,
• Transient hallucinations,
• Illusions, and
• Delusions.

Detection of ADRs
Pre- Marketing Studies Post– Marketing Surveillance
Spontaneous
adverse
reaction
reporting
Epidemiological
methods
Case Control
Studies
Cohort
Studies
Phase 1
Phase 2
Phase 3

PRE- MARKETING STUDIES
•Animal Models
•Risk information
,acute toxicity &
which organs are
affected .
•Safety test
•3 phases of clinical
trails
•Consequences

POST- MARKETING STUDIES
●
•

•These methods are used to verify the link between drug exposure and an
adverse outcome.
•Two epidemiological methods most commonly used are:
Cohort Studies
Case Control
Studies
Epidemiological studies
Advantage: Reveals unsuspected ADRs Advantage: Can be analysed quickly as number
of patients analysed is small.

• Patient initials,
•Age at onset of reaction,
•Reaction term(s),
•Date of onset of reaction,
• Suspected medication(s)
• reporter information.
Mandatory field for suspected
ADR reporting form.

•
•
More rational
Prescribing
Better communication
Consider risk
factors for ADRs
Patient counseling
Better monitoring
of treatment
70% ADRs are potentially
avoidable
Preventing ADR

Medical maloccurrence
● In some cases inspite of good medical attention and care ,an
individual fail to respond properly or may suffer from adverse
reactions of the drug .
● The injured person cannot get compensation
● Doctor was careful in selection of the drugs and has taken
appropriate measures to overcome this effects.

Therapeutic misadventure
Mischance or accident or disaster ,in which individuals may be
injuried or died due to some unintentional act of doctor or
hospital .
3 types-therapeutic ,diagnostic , experimental
It is known that many of the therapeutic procedure cause death to
patient ,the doctor is not directly responsible for the harm.
Radiological procedure(contrast) cause fatal adverse reactions

Contributory negligence
● In this condition patient is also responsible for the injury
suffered by him.As such doctor is not the direct , cause of the
injury suffered by the patient.
● Failure to give proper history ,cooperation,refusal to treatment
,against doctors advice .

References:
•Goodnman& gilmans phamacologicalbasisof therapeutics13 thedition
•K.DTripathi–Essentialof pharmacology-6th edition
•Lippincottillustratedreview–Pharmacology-6th edition
•Bardalae principlesof forensicmedicicne& toxicology.
•Anil Aggrawal textbookof forensicmedicineandtoxicology
•Narayanareddy textbookof forensicmedicine andtoxicology

If you suspect an ADR do
not assume someone else
will report it……

Drug idiosyncrasy

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