BANGALORE - 560064

MISBA ANJUM
VII SEM B PHARMACY

TOPIC : Adverse Drug Reactions

SUBJECT : Pharmacy Practice
SUBMITTED TO : Dr. Shibi Mary Thomas
According to WHO ( World Health Organization),
Adverse Drug Reaction (ADR) can be defined as a
response to a medicine which is unintended or
unwanted or noxious effect of a drug which occurs at
therapeutic doses in humans used for the prevention,
prophylaxis, diagnosis and treatment of a disease.”
1) Overdose of the drug
2) Therapeutic errors
3) Drug abuse or dependnace
 Harm associated with the use of a given
medications
OR
Unwanted or harmful reaction experienced
after the administration of a drug or
combination of drugs under normal
conditions of use
 ADR= morbidity & mortality
Mild reactions :Drowsiness,nausea,itching& rash
which disappear after discontinuation of drug

Severe reactions: Respiratory depression

Neutorpenia
Haemorrhage
ADR most common in

Women
Elderly (>60 y old)
Very young (1-4 y)
Patients taking more than one drug
 PREDISPOSING FACTORS ASSOCIATED WITH ADR

Patients who have one or more of the following predisposing

factors are at high risk of developing ADRs.
1. AGE
Incidence of ADR increases with age.
Especially the neonates and elderly are more vulnerable to
develop ADRs. (Due to the physiological changes)
 because of the inefficiency of vital systems of the body involved
in metabolism and excretion.
2. SEX
 Females are at greater risk to ADRS than males. This may be
due to the following reasons.
 Differences in pharmacokinetics and
Pharmacodyanamic b/w males and females due to
the difference in their body physiology.
 Hormonal make up of males and females differ.
 Females take more medications than males.
 Due to social reasons, women volunteers do not
come forward for the clinical trails. Hence, much
clinical research cannot be carried out and ADRS
cannot be studied in case of females as thoroughly as
in case of males.
3. DRUG CHARACTERSTICS
Some drugs are highly toxic in nature and patients who
are treated with these agents are at an increased risk
of ADRs. For eg: nausea and vomiting is a common
adverse drug reaction seen in patients treated with
anticancer drugs.
Patients who are treated with drugs which have a
narrow therapeutic index are more susceptible to
develop ADRs., as a slight increase in the serum
concentration of these drugs may result in drug
toxicity.
Eg : Digoxin , Gentamycin
4. DURATION OF THERAPY
If the therapy is continued for more than the required
period of time , then may leads to ADR.
5. RACE AND GENETICS
It is evident that ADRs are more common in
genetically predisposed individual.
Eg : Patients who are genetically deficient of glucose 6
phosphate dehydrogenase (G6PD) enzyme are at higher
risk of developing hemolysis due to primaquin
6. POLY PHARMACY
Patients with multiple drug therapy are more prone to
develop an adverse drug reaction either due to
alteration of drug effect through an interaction
mechanism.
The amount of risk associated with multiple drug
therapy increases in direct proportion to the number of
drugs administered.
7. Medication error
Self medication of OTC drugs by patient leads to over
use or misuse of drug. It may result into excess
pharmacological action or complications.
8. Inadequate monitoring of the patient.
Drugs like cardiotonics, diuretics , corticosteroids,
needs therapeutic monitoring with continuing the
administration beyond therapeutic effect end point
which leads to adverse reactions.
Therapy with drugs like corticosteroids and
hormones cannot be suddenly stopped,such drugs
therapy is gradually stopped by decreasing the dose.

Drug interaction and drug food interaction

This also produce adverse effect.
Rawlin & Thompson classification
Traditional classification

1) Type A Reactions
a) Related to pharmacological action of drug
b) Predictable
c) Common
d) Dose – dependent
About 80% of ADR----Type A reactions
 TypeA reactions Classes
i) Toxicity / Toxic effects
ii) Secondary effects
iii) Side Effects
iv) Intolerance
i) Toxicity of overdose (Drug overdose)
An adverse drug reaction caused by excessive dosing
Repeated admnistration of the drug which leads to
toxicity. This can change physiological functions or
can damage the organs in the body. The
exaggerated pharmacological effect of the drug
leads to toxicity.
Eg: hepatic failure with dose of paracetamol
streptomycin with ototoxicity
hypoglycemia with sulfonylurea;
ii) Side Effects
Nearly unavoidable secondary drug effect produced by
therapeutic doses
They are undesired or unwanted pharmacological
actions of the drugs, when they are given in
therapeutic doses. Most of the side effects are harmful,
only some are beneficial.
Intensity is dose dependent
Occur immediately after initially taking drug or may
not appear until weeks after initiation of drug use.
Eg : Oral antidiabetic - hypoglycemia
 Eg : Atropine causs dryness of mouth. Due to this
side effect it can be used as a pre-anaesthetic
medication for the control of secretions.
Eg : sedation with antihistamines
Eg : Aluminum hydroxide gel causes constipation
iii) Secondary Effects
Secondary pharmacological effect
A drug may contain no of pharmacological effects
at therapeutic doses. An indirect effect is
produced simultaneously along with the primary
or desired action. The indirect effect of a drug is
known as secondary effect.
Eg : Thiazide diuretics used for treating HTN
causes hypokalemia
Eg:Antihistamines used as anti allergy – sedation
Some individuals cannot tolerate the normal
therapeutic doses of the drugs not even when
administered in small doses, as well as this may cause
toxic effects in the individuals.
Drug effects :
Chloroquine tablet : Noxious , abdominal pain and
(normal or less dose) vomiting
Unrelated to known pharmacological
actions of drug.
 Bizarre Unpredictable
Often caused by immunological &
pharmacogenetic mechanisms
Unrelated to dosage
Comparatively rare & cause serious illness
or death
Eg : Penicillin causes Anaphylactic shock
Both environmental & genetic factors =
important in this reaction.
It includes :
i) Idiosyncratic reactions or idiosyncracy
ii) Allergic or hypersensitive reactions
Type B reactions classes
i) Idiosyncratic reactions or idiosyncrasy:
They defined as qualitative intolerance
where abnormal reactions to drugs are precipitated
due to Genetical abnormality or absence of
enzymes.
This occurs in only some individuals who are
genetically abnormal or peculiar.
Ex- Individuals who are deficient of glucose -6-
phosphate – dehydrogenase in their RBC
Shows idiosyncratic effect ( haemolysis) upon
administration of drugs like primaquine (antimalarial)
salicylates( NSAIDs) sulfonamides (antibiotics).
ii) Allergic or hypersensitive reactions
Allergic or hypersensitive reactions are defined as
abnormal or altered reactions towards an antigen
( generally referred to allergen ) including more or less
sensitivity or untoward immunological reactions.
It is used to indicate the hypersensitivity of the body
cells to the drug.
TYPES :
Type-I : reaction mediated by IgE antibodies
Type- II : cytotoxic reaction mediated by IgG or IgM
antibodies.
Type-III : reaction mediated by immune complexes.
Type-IV : delayed reaction mediated by cellular response.

Mechanism involved in the allergic reactions:

Drugs and its metabolites bind with the body proteins.
After binding, they can act as antigen or haptens
( incomplete antigens). The antigens or haptens stimulate
antibody production or T- lymphocytes
( sensitized). When such a sensitized individual is given
the same drug for the second time, it leads to the
formation of antigen- antibody complex. This antigen-
antibody complex stimulates or triggers histamine
release into blood circulation, resulting in allergic or
hypersensitive reactions.
 Eg: Penicillin and Sulfonamides cause allergic
reactions in some individuals
3) Type C reactions ( prolonged use
reactions)
They are rare ,dose and time dependent.
These reactions are seen upon cumulative
administration of the dose of a drug.
This results from prolonged use of the drugs
Associated with long-term drug therapy
Well known and can be anticipated
This results from prolonged use of drug
Eg- prolonged use of corticosteroids causes
adrenal suppression.
E.g. benzodiazepines causes drug dependence
Type D reactions are uncommon and generally dose
dependent..they are delayed reactions
Very rare,, dose dependent , uncommon
Effects :
A) Teratogenicity - Drug- induced birth defects
B) Carcinogenicity - Medication lead to cancer
Teratogenicity- it is defined as the property of
producing deformity in developing embryo.
When drugs especially antibiotics are given to a
pregnant woman, it can lead to the development of
foetal abnormalities.
Drugs ( agents) which cause deformities in the
developing embryo are known as teratogens.
Most of the drugs cause the placental barrier in the
first 3 months.
Eg: Thalidomide is the best example. It causes
phocomelia when administered in the first trimester.
Thalidomide was prescribed to pregnant women
against morning sickness which lead to the
development of phocomelia (seal limbs) in the new
born.
Eg: Anti neoplastic drugs- multiple birth defects.
Tetracycline- retadation of bone growth,
Carcinogenicity- Ability to produce cancer or
malignancy. Any substance or agents that cause
development of cancerous growth in the living tissues
are known as carcinogenic agents or carcinogens.
It takes > 20 years to develop
 5) Type E
(Withdrawal symptom reactions)
Rare
Dose dependent.
These reactions are associated with withdrawal
symptom , which results from sudden discontinuation
of prolonged use of drugs or abused drugs.
Ex. Opioids, barbiturates causes withdrawal symptoms
due to sudden withdrawal of drug.
Other types.
A) Iatragenic ( drug induced)
Dugs or agents which include the diseases in the
body by disturbing physiological functions are called
iatragenic.
Eg : salicylates – peptic ulcer
 phenothiazines- parkinsonism
B) Photoallergic reactions
Some drugs like fluoroquinolones, sulfones etc cause
skin rashes. These drugs can induce skin sensitivity
to u.v rays.
Sign & Symptoms of ADR
Mild, moderate, severe or lethal
Sign & symptoms manifest soon after 1st dose or
only after chronic use
e.g., Allergic reactions occur soon after drug is taken
usually 2nd time ( itching, rash, eruption, upper or
lower airway edema with dyspnea & hypotension)
 Role of pharmacists in the prevention of adverse
drug reaction
 Pharmacists plays a major role in prevention of ADR.
 He advices the patient regarding the safe use of drugs.
 He has to detect the adverse reactions by asking the
patient different questions related it.
 He should carefully check the patient medication
history and drug profile records before dispensing
medicines to the patient.
 A) review of literature.
 A pharmacist should review the complete literature
about the drug like labels, leaflets in the packaged
drugs.
B) Identification of adverse effects
 He should identify the symptoms towards adverse
reactions experienced by the patients like rashes,
itching or other effects etc.
C) Medication history of the patient
 Collect past and present history of the patient.
 Previous allergic reactions.
 Social habits and food habits.
D) Drug profile study
Pharmacist should study the drug profile record
which contains the complete information about the
drug.

E) Capability of taking therapeutic decisions

.pharmacist must have the ability to suggest the
alternative therapy in place of a drug which cause
adverse drug reactions in order to provide patient
complaince.
He should avoid multiple drug therapy if
possible.
.
 F)ADR Reporting
 Hospital; pharmacist is the responsible person
 He should detect the causes for adverse drug
reactions
 From drug profile and patient medication history
records.
 Pharmacist notices any suspected adverse effect or
therapeutic errors, then he must immediately report
to the physician.
 He should enter the complete information into
patient MPR.
Assessing causality
Causality assessment is the method by which the
extent of relationship between a drug and a suspected
reaction is established.
If an ADR is suspected, the assessment starts with
collection of all the relevant data pertaining to
patient demographics, medication history interview,
including non- prescription drugs(OTC).
ADR details including a description of the reaction,
time of onset and duration of reaction, complications,
treatment of the reaction and outcome of the
treatment and relevant investigations report.
The collected data should be used to correlate and
categorize the relation ship b/w the suspected drug
and ADR
In the first approach , an individual who is an expert in
the area of ADRs would evaluate the case.
In the process of evaluation, they may consider and
critically evaluate all the data obtained to assess
whether the drug has caused the particular reaction.
Using formal algorithms to detect ADR.
Naranjos scale, WHO scale, European ABO system,
Kramer method etc.
 To assess the adverse drug reaction, please answer the following questionnaire and give the pertinent score.
Ye s No Do Not Know Score
1. Are there previous conclusive reports on +1 0 0 ____
this reaction?
2. Did the adverse event appear after the +2 -1 0 ____
suspected drug was administered?
3. Did the adverse reaction improve when the +1 0 0 ____
drug was discontinued or a specific
antagonist was administered?

Naranjo ADR 4. Did the adverse reactions appear when the

drug was readministered?
+2 -1 0 ____

Probability Scale
5. Are there alternative causes (other than the -1 +2 0 ____
drug) that could on their own have caused
the reaction?
6. Did the reaction reappear when a placebo -1 +1 0 ____
was given?
7. Was the drug detected in the blood (or +1 0 0 ____
other fluids) in concentrations known to be
toxic?
Naranjo CA. Clin Pharmacol 8. Was the reaction more severe when the +1 0 0 ____
dose was increased, or less severe when the
Ther 1981;30:239-45 dose was decreased?
9. Did the patient have a similar reaction to +1 0 0 ____
the same or similar drugs in any previous
exposure?
10. Was the adverse event confirmed by any +1 0 0 ____
objective evidence?
Total Score ____

Total Score ADR Probability Classification

9 Highly Probable
5-8 Probable
1-4 Possible
0 Doubtful
 Detecting ADR

 Documentation of ADR

 Reporting serious ADR to AMC

 Assessing causality between drug and reaction

THANK
YOU