ADVERSE DRUG

REACTIONS
Dr. Manjunath.G.N
SSMC
Tumkur
 Definition
• Any response to a drug that is
noxious and unintended and that
occurs at doses used in man.
 Types
• Dose related (Predictable – type A)
• Non dose related (Unpredictable –
type B)
• Long term effects
• Delayed effects
 Severity
• Mild
• Moderate
• Severe
• Lethal
 Incidence
• Hospital in-patients – 10-20%
• Deaths in hospital in-patients - 0.24-
2.9%
• Hospital admissions – 0.3-5%
 Classification of ADR
• Dose related
1.Pharmaceutical variation
2.Pharmacokinetic variation
a) Pharmacogenetic variation
b) Hepatic disease
c) Renal disease
d) Cardiac disease
3.Pharmacodynamic variation
a) Hepatic disease
b) Altered fluid and electrolyte imbalance
 Contd.
• Non dose related
a) Immunological reaction
b) Pharmacogenetic variation
• Long term effects
a) Adaptive changes
b) Rebound phenomena
c) Other long term effects
 Contd.
• Delayed effects
a) Carcinogenesis
b) Effects connected with reproduction
a) Impaired infertility
b) Teratogenesis
c) Drugs in breast milk
 Various ADR
• Side effects
• Secondary effects
• Toxic effects
• Intolerance
– quantitative
- qualitative 1. Idiosyncracy
2. Hypersensitivity
• Photosensitization
 Contd.
• Drug withdrawal reaction
• Drug dependence
• Teratogenecity
• Carcinogenecity/mutagenecity
• Iatrogenecity
 Manifestations of ADR
• Haemopoietic toxicity
• Hepatotoxicty- direct
immunological
• Nephrotoxicity
• Ocular toxicity
• Ototoxicity
 Contd.
• Behavioural toxicity
• Electrolyte imbalance
• Endocrine disturbance
• Skin toxicity
• Unmasking and exacerbation of
disease
• Acute withdrawal reaction
 Contd.
• Carcinogenesis
• Teratogenesis
• Alteration of taste
• Drug dependance
 Pharmacovigilance
widening horizons
• Illegal sale of medicines and drugs of
abuse on internet
• Increasing self medication practices
• Widespread manufacture and sale of
counterfeit and substandard medicines
• Increasing use of traditional medicines
outside the confines of traditional culture
• Increasing use of traditional medicines and
herbal medicines with other medicines
 Pharmacovigilance
• French term- detection, assessment,
understanding and prevention of
adverse drug event
 Partners in
pharmacovigilance
• WHO quality assurance and
safety;medicines team
• Uppasala monitoring center
• National pharmacovigilance centers
• Pharmaceutical industry
• Hospitals
• Health professional
• Patients
• Other partners
 What is ADR
monitoring ?
• Systemically collecting information
about adverse drug experiences with
the aim of, through feed back to the
parties involved, contribute to
continuously improving drug therapy.
 Aim : To detect
• Serious unexpected ADRs
• Increased or unexpectedly high
frequency of known significant ADRs
• To prepare list of ADRs not
previously reported
• To disseminate the information
through regular bulletins, reports,
and articles in the press
 Surveillance methods
• Anecdotal reporting
• Voluntary reporting
• Intensive event reporting
• Cohort studies
• Case control studies
• Population statistics
• Record linkage
• Meta analysis
 Need for monitoring
• Short coming of premarketing studies-which
reveal most common and acute untoward effect
• Increase cost of patient care
• Medication : 10-57% is self medication
• Our country has vast population, poverty and rich
research ground
• Accelerated approval and rapid introduction of
new drugs
• Paucity of ADR data
 Who reports ?
• Doctors-hospital level, Medical
officer from PHC’s, GP’s
• Dentists
• Drug manufacturers
• Pharmacists and nurses
 Types of ADR
Type Type of effect Features examples
A Augmented Common, predictable, low mortality Bradycardia–β-blockers

B Bizarre Uncommon, unpredictable, high morbidity Anaphylaxis - Penicillin

& high mortality
C Chronic Dose related & time related Dyskinesia - Levodopa

D Delayed Time Related Teratogenesis

E End of use Withdrawal of chronic therapy abruptly Corticosteroids

F Failure Unexpected failure of therapy Oral contraceptive failure

- Rifampin
 What to report ?
• New drugs – all suspected adverse reaction
• Established drugs
- All serious reactions-well recognized
- All reactions to vaccines
- Unexpected high frequency of a known
adverse reaction
- All reactions to pregnant & lactating
women including new born
 Where to report ?
• Nearest ADR monitoring centers
• Peripheral centers
• Regional centers  national center at
new Delhi
• Directly on internet
www.fda.gov/MedWatch
 Importance of ADR
reporting
• Early detection of unknown safety
problems
• Detection of increases in frequency
• Provides early detection of warning signals
• Evaluates pattern of adverse effect
• Measures incidence of adverse effects
• Improves therapy
 Reasons not to report
• Uncertain association
• Too trivial to report
• Too well known to report
• Unaware- existence of national center
• Unaware- of the need of to report of ADR’s
• Not enough time
• Non availability of ADR forms
• Too bureaucratic
• Legal issues
• Lack of feed back