ADR

1. Adverse drug reaction
&
ITS MONITORING
Presented by
Abhishek Mondal
1st m pharm
Dept of pharmacology
Submited to
Mr mukund handral sir
Asst prof .
Dept of pharmacology

2. Definition
• Adverse Event (AE): Any untoward medical occurrence that
may present during treatment with a pharmaceutical product
but which does not necessarily have a causal relationship with
this treatment.
• WHO defines Adverse Drug Reaction as:
Adverse Drug Reaction (ADR): Any noxious change which is
suspected to be due to a drug, occurs at doses normally used
in man, requires treatment or decrease in dose or indicates
caution in future use of the same drug.
• Therefore, an adverse drug reaction is an adverse event with a
causal link to a drug.

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as a non barbiturate hypnotic & for morning sickness
during pregnancybased on animal toxicity report.
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outbreak of PHOCOMELIA (hypoplastic and aplastic
limb deformities) in the new born babies
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5. Classification of ADRs
• Depending on….
• Onset of event: Acute (<60 minutes), Sub-acute (1-24 hrs)
and Latent (>2 days)
• Type of reaction: (Wills and brown)
• Type A (Augmented), B (Bizarre), C (Chronic),
• D (Delayed), E (End of treatment)
• Severity: Minor, Moderate, Severe, Lethal ADRs
• Others: Side effects, Secondary effects, Toxic effects,
Intolerance, Idiosyncrasy, Drug allergy, Mutagenicity,
Photosensitivity, Drug Dependence, Drug Withdrawal
Reactions, Teratogenicity, Carcinogenicity, Drug induced
disease (Iatrogenic).

6. Type A (Augmented) reactions
• Reactions which can be predicted from the
known pharmacology of the drug
• Dose dependent
• Can be alleviated by a dose reduction
• Common Skilled management reduces their
incidence.
• E.g.
• Anticoagulants Bleeding
• Beta blockers Bradycardia
• Nitrates Headache
• Prazosin Postural hypotension

7. Type B (Bizarre) reactions
• Predictable where the mechanism is known, otherwise
unpredictable for the individual, although the incidence
may be known.
• Dose independent, rare
• Host dependent factors important in predisposition
• These account for most drug fatalities.
• E.g. Penicillin Anaphylaxis,
• Anticonvulsant Hypersensitivity

8. Type C ( Chronic)
• Reactions due to long time exposure.
• e.g. Analgesic neuropathy
• Dyskinesia with levodopa

9. Type D (Delayed) reactions
• Occur due to prolonged exposure.
• Can be due to accumulation.
• E.g.
• Carcinogenesis, or short term exposure at a
critical time e.g.teratogenesis.

10. Type E (End of use) reactions
• Occur on withdrawal especially when drug is
stopped abruptly
• E.g.
• Phenytoin withdrawal Seizures
• Steroid withdrawal Adrenocortical insufficiency.
• opioid causing the withdrawal syndrome.

11. 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.

12. Side effects
• Unwanted but often unavoidable, occur at therapeutic
doses
• Predicted from the pharmacological profile of a drug
• Known to occur in a given percentage of drug recipients
• E.g.
• Atropine dryness of mouth
• Promethazine (anti-allergic) sedation
• Codeine(anti-tussive) constipation Used in Traveller’s
diarrhoea

14. Predictable toxic effects
• Dose dependent adverse effect may be –
• Direct damaging effect to tissue e.g. Paracetamol
overdose leads to hepatotoxicity, Aminoglycoside
(Gentamicin) causes nephrotoxicity.
• Rebound response – ( due to R-upregulation) abrupt
withdrawl after chronic use. e.g.propranolol stoppage
leads to precipitation of MI, Glucocorticoid withdrawal
leads to acute adrenal insufficiency.morphine – due to R
supersensitivity.

16. Unpredictable toxic effects
• Dose independent
• Less than therapeutic dose may lead to toxic
effect

17. Idiosyncrasy
• unusual response to a drug due to genetic abnormality.
• Drug interacts with some unique feature of the individual,
not found in majority subjects, and produces the
uncharacteristic reaction.
• E.g.
• Isoniazid: N-Acetylation affects the metabolism of
isoniazid
• Slow N-Acetylation: Isoniazid is more likely to cause
peripheral neuritis.
• Fast N-Acetylation:cause hepatotoxicity in this

18. Drug allergy
• Acquired, altered reaction of the body to drug.
• Immunologically mediated reaction.
• occur even with much smaller doses
• Also called Drug hypersensitivity
• Not genetic,not occurred in all
• Occurs on reexposure
• E.g. penicillin→1st time →stimulate antibody →Ag-Ab
reaction →allergy
• Chief organ: Skin, respiratory tract,GIT,Blood & blood
vessels

19. Intolerance
• Appearance of characteristic toxic effects of a drug in an
individual at therapeutic doses
• Converse of tolerance
• Indicates a low threshold of the individual
• E.g.
• Triflupromazine (single dose) Muscular dystonias in
some individuals
• Carbamazepine (few doses) Ataxia in some individuals
• Chloroquine (single tablet) Vomiting and abdominal
pain in some individuals

20. ADR MONITORING
• Identifying Adverse Drug Reaction
• Assessing Causality (Relationship between
drug and suspected reaction)
• Documentation of ADR
• Reporting Serious ADRs to
Pharmacovigilance centres /ADR
Regulating Authorities

23. Causality Assessment Between Drug and
Suspected reaction
• Assessment performed by usually 2 methods include:
• Clinical Judgment
• An individual who is an expert in the area of ADRs would
evaluate the case
• Algorithms
• Commonly used algorithm is the Naranjo algorithm

25. Documentation of ADRs
• Documents used for Reporting ADRs:
• Source Documentation
• eg. Patient's Medical Records, X-Ray or Diagnostic
Reports
• AE/SAE Forms
• Paper Case Report Form (CRF)/ Electronic CRF

27. Reporting Serious ADRs
• Information to be Captured for Reporting includes the
following:
• Patient details
• Initials
• Gender
• Age and date of birth
• Weight
• Height

28. SUSPECTECTED DRUGS
• Generic name of the drug
• Indication(s) for which suspect drug was prescribed or tested
• Dosage form and strength
• Daily dose and regimen (specify units - e.g., mg, ml, mg/kg)
• Route of administration
• Starting date and time of day
• Stopping date and time, or duration of treatment
• Other Treatment(s)
Concomitant drugs

29. • Details of Suspected Adverse Drug
Reaction(s)
• Full description of reaction(s) including body site and severity, as well
as the criteria for regarding the report as serious,whenever possible,
describe a specific diagnosis for the reaction
• Start date (and time) of onset of reaction
Stop date (and time) or duration of reaction
Outcome
• Information on recovery; results of specific tests and/or treatment
• For a fatal outcome, cause of death and its possible relationship to
the suspected reaction; any post-mortem findings
• Any Other information relevant to facilitate assessment of the case,
such as medical
• history of allergy, drug or alcohol abuse; family history; findings from
special investigations etc

30. Reporting Responsibilities
Responsibilities of Sponsor
• SAEs should be reported to the licensing authority within
14 calendar days of awareness
• Submit status report (Periodic Safety Update Reports) to
the licensing authority periodically
Responsibilities of Investigator
• SAEs and unexpected AEs should be reported to the
sponsor and licensing authority within 24 hrs
• To their respective Ethics Committee within 7 working
days