The document discusses drug safety and adverse drug reactions. It provides details on some major drug safety issues like the sulfanilamide tragedy in 1937 which caused over 100 deaths. It also discusses thalidomide and the phocomelia birth defects it caused. The document defines an adverse drug reaction and adverse drug event. It describes different types of reactions like dose-related (Type A), unpredictable (Type B), chronic, delayed, end of dose, and treatment failure. It also discusses concepts like drug dependence, teratogenicity, withdrawal reactions, and pharmacovigilance.

1. Drug safety , Adverse drug
reaction , PvPI
Dr.V.Krishnan
M.D ( Stanley Med College ) , C.diab

2. Sulphanilamide tragedy in U.S
• Elixir sulfanilamide was an improperly
prepared sulfanilamide medicine that caused
mass poisoning in the United States in 1937. It
caused the deaths of more than 100 people.
• Diethyleneglycol solvent mediated damage.

3. Thalidomide –Phocomelia tragedy -1960

4. • Adverse drug reaction ‘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 the future use of the same drug’
• Adverse drug event ‘any untoward medical
occurrence that may present during treatment
with a medicine, but which does not
necessarily have a causal relationship with the
treatment’

5. Type Characteristics
A-Augumented Predictable , May be preventable . Usually less serious
Eg .Aspirin causing gastritis .
B-Bizzare Unpredictable , Immunological or genetic reactions .
Usually more serious Eg. Phenytoin causing SJS
C-Chronic Due to long term use of drug . Eg .Steroids causing diabetes
D-Delayed After long exposure and after treatment . Eg. Tardive
dyskinesia due to antipsychotics.
E-End of dose effect Eg .Acute adrenal crisis due to sudden stoppage of drug
F-Failure of treatment Eg .Antibiotics failure in treating infection
G -Genotoxic Damaging genome
H-Hypersensitivity Immunological reaction

6. • Side effects
• Type A reaction
• These are unwanted but often unavoidable
pharmacodynamic effects that occur at
therapeutic doses
• Usually mild , Can be reduced by reducing dose of
a drug
• This may be due to same desired pharmacological
action Eg. Betablocker reducing heart rate
beneficial in IHD but prone to cause heart block
• May be due to another pharmacological action .
• Eg. Codeine used to suppress cough can cause
constipation due to its antimotility,antisecretory
effect on intestine

7. •
• Secondary effects
• Type A reaction
• These are indirect consequences of a primary
action of the drug,
• Eg .Steroid immunosuppression can activate
tuberculosis in an individual

8. • Toxic effect
• Type A - The manifestations are predictable
and dose related
• These are the result of excessive
pharmacological action of the drug due to
over dosage or prolonged use
• This may occur at normal dose also when
body physiology is altered Eg.In Renal failure
patients Gentamycin normal dose can be toxic
• Toxic effect may result in poisoning - Implies
harmful effects of a chemical on a biological
system

9. • General management of poison cases
• Airway maintenance
• Breathing assistance using O2/Ventilators
• Circulatory maintenance by IV fluids
• Decontamination of poison from body-Washing ,
Gastric lavage
• Prevent further exposure . Eg.Further absorption
from stomach by giving Activated charcoal
• Eliminate by alkanisation of urine or acidification
of urine or by haemodialysis
• Specific management
• By giving specific antidote
• Eg . Naloxne used in morphine poison

10. • Intolerance
• It is the appearance of characteristic toxic effects
of a drug in an individual at therapeutic doses
• It is type B reaction
• But usually milder than immunological or genetic
reaction
• It indicates that patient having low threshold to
develop adverse effect to that drug
• Eg . One tablet of chloroquine may cause
vomiting and abdominal pain in an occasional
patient

11. • Idiosyncrasy
• It is type B –Bizarre , Unpredicatble reaction
• It is genetically determined abnormal reactivity to a
chemical.
• The drug interacts with some unique feature of the
individual,
• It is restricted to individuals with a particular genotype
• Single nucleotide polymorphism is the major cause for such
reactions
• Genomic screening may be useful in future to screen such
individuals
• When such susceptibility is detected , their can treatment
can be modified for them , Personalized medicine.
• Eg . Dapsone induced Hemolysis in G6PD deficient patients

12. • Drug allergy
• It is an immunologically mediated reaction
producing stereotype symptoms which are
unrelated to the pharmacodynamic profile of
the drug,
• Have a different time course of onset ,
Immediate or late
• DO not have dose dependent relationship
• May be more severe than expected

13. • Drug allergy –Types
• Type-I IgE – Anaphylactic reactions
• Eg . Penicillin induced analylaxis causing
hypotension , bronchospasm , shock etc.
• Type-II (cytolytic) reactions
• Eg .Methydopa induced hemolytic anaemia
• Type-III ( Arthus) reactions
• Gold induced Membranous nehpritis
• Type-IV (delayed hypersensitivity) reactions
• Silver cream causing contact dermatitis

14. • Drug allergy treatment
• Type I
• Airflow , Breathing maintenance
• IV fluids , Electrolyte and blood sugar balance
• Inject adrenaline 0.5 mg (0.5 ml of 1 in 1000
solution for adult) i.m
• IV hydrocortisone -100 mg stat
• Inj .Chlorpheniramine , antihistamines 10mg im
• For type II , III , IV
• Glucocorticoid can be given depending on
severity
• Severe cases –Methylprednislone IV
• Mild –Moderate cases –Prednislone 5-60mg/d

15. • Photosensitivity
• It is a cutaneous reaction resulting from drug
induced sensitization of the skin to UV radiation.
Phototoxic Phtotallergic
Drug or its metabolite accumulates in the
skin, absorbs light and undergoes a
photochemical reaction
Drug or its metabolite induces a cell
mediated immune response
The shorter wave lengths (290–320 nm,
UV-B) are responsible.
Longer wave lengths (320–400 nm, UV-A)
produces this reaction
May be acute Eg.By tetcycline or chronic May be acute antibody mediated or chronic
Eg. Sulphonmise causing skin toxicity
It is more common , less severe It is less common but may be more severe
It is type B , unpredictable reaction , Can
be minimized by less exposure to sunlight
It is type B , unpredictable reaction , may be
preventable in next episode by avoiding
such drug

16. • Drug dependence
• Drugs capable of altering mood and feelings
are liable to repetitive use to derive euphoria,
recreation, withdrawal from reality, social
adjustment, etc.
• This is due to reinforcing nature of substance
mediated by dopamine release in brain
• Drug dependence is a state in which use of
drugs for personal satisfaction is accorded a
higher priority than other basic needs, often
in the face of known risks to health.

17. Physical dependence Psychological dependence
It is an altered physiological state
produced by repeated
administration of a drug which
necessitates the continued presence
of the drug to maintain physiological
equilibrium
It is said to have developed when
the individual believes that optimal
state of wellbeing is achieved only
through the actions of the drug
This is due to altered physiological
state created by drug
This is due to reinforcement
behaviour of drug
Withdrawal reaction , Craving are
more and severe
Withdrawal reaction Craving present
, Less than physical dependence
Drug addiction usually proceeds Drug habituation usually precedes
Usually due to continuation of
physician advice , after the necessary
period
Mostly seen with self medication
Eg.Cough suppressants
Usually seen with chronic
medications Eg.Barbiturates ,
Diazepam
Usually seen with rapid acting ,
producing ‘Kick’response

18. • Teratogenicity
• It refers to the capacity of a drug to cause foetal
abnormalities when administered to the pregnant
mother.
• Came into widely known after Thalidomide casuing
Phocomelia-Sealed limbs when used for pregnant
woman for morning sickness
• Drugs can affect the foetus at 3 stages
• Fertilization and implantation—conception to 17
days—failure of pregnancy which often goes
unnoticed.
• Organogenesis—18 to 55 days of gestation—most
vulnerable period, deformities are produced.
• Growth and development—56 days onwards —
developmental and functional abnormalities can occur

19. • Teratogenic Risk Category
• A-No risk to fetus . Eg . Levothyroxine
• B – No evidence of risk in humans Eg. Amoxycillin
• C- Risk cannot be ruled out Eg. Morphine
• D- Risk outweigh benefits –Eg.Phenytoin
• X-Absolute risk present – Isotretinoin
• Prevention
• Avoid any drug during first trimester
• If needed , select most safer drugs for short duration.
• Take all the precautions Eg.Folic acid 4mg daily during
conception , prevent neural tube defects due to drugs
• Do USG at 20 th weeks of gestation , If teratogenicity
detected , Do termination of pregnancy

20. • Drug withdrawal reaction
• Eg.Acute adrenal crisis after sudden stoppage
of steroids
• Mutagenicity and carcinogenicity
• Eg .Ionising radition or anticancer drugs itself
can cause second tumours
• This is usually tested in chronic toxicity studies
in animals
• But sometimes , unpredictable and
unavoidable due nonavaialbility of other drugs

21. • Drug induced diseases
• These are also called iatrogenic (physician
induced) diseases, and are functional
disturbances (disease) caused by drugs which
persist even after the offending drug has been
withdrawn and largely eliminated,
• e.g.: Peptic ulcer by corticosteroids

22. • Drug induced diseases , in general all adverse
effects can be reduced or prevented by .
1. Proper history taking regarding drug allergy
2. Selecting suitable drug , dose , duration .
3. Avoiding prolonged treatment or
polypharmacy
4. By lab monitoring if applicable , like LFT , RFT
etc
5. By reporting all adverse effects so that it can
be prevented in future

23. • Pharmacovigilance
• Defined as ‘science and activities relating to the
detection, assessment, understanding and prevention
of adverse effects or any other drug related problems.’
• India National Pharmacovigilance programme initiated
in 2004 , Since 2010 It is PvPI , functioning by Indian
Pharmacoepia Commisiion , Gazhidabad
• It has National , zonal, regional , peripheral centres to
collect ADR reports
• From India , It goes to WHO- Uppsala Monitoring
centre , Sweden
• There ‘Signal’ detection[ First generated adverse effect
risk or suspicion of drug ] takes place following wide
scale causality assessment using Naranjo or WHO scale
.

24. PvPI programme functions
• To create a nation-wide system for patient
safety reporting
To identify and analyse new signal from the
reported cases
To analyse the benefit - risk ratio of marketed
medications
To generate evidence based information on
safety of medicines
To support regulatory agencies in the decision-
making process on use of medications

25. • ADR can be collected by
• Pharmacovigilance studies
• Data from drug utilization research
• Data from clinical trials
• Post marketing surveillance after drug approval
through PSUR [Periodic safety update report]
• Data mining from hospital records
• Following , Case records , Disease register
• Pharmacogenomic studies
• Spontaneous drug reporting –Through forms ,
mail or adr mobile apps etc.

26. • Must to know questions
• Define ADR. Describe various drug reaction
with example
• Drug allergy
• Teratogenicty
• Pharmacovigilance
• Iatrogenic disease
• Diff Bet Side effect , secondary effects
• Diff Bet toxic effect and Intolerance

27. adr Mobile App in
Android to report adverse
drug effect
ADR form now can be filled by
patient in Tamil , English or
hIndi etc .
Hemovigilance ,
Materiovigilance programme is
also started in India

28. • Recent advances
• Clinical Scenario
• Clinical Implications
• MCQs-[ AIPG , AIIMS , PGI , USMLE ]
• Refer my class notes
Thank You
Dr.V.Krishnan
M.D ( Stanley Med College ) , C.diab

29. Always ask your
patient ,
Allergy history
Family allergy history
Drug allergy

30. Explain all the possible
adverse effects to your
patient , and tell them ways
to minimize it

31. Always ask
concomitant
drug intake
Remember
even herbal
drugs can cause
ADR

32. A 24 year old male admiited in hospital for fever , receiving
Antibiotic Amikacin , Paracetamol , Ranitidine . On 3rd day , Pt
is relieved of fever lab parameters are normal except elevation
of creatinine from 1 mg/dl to 1.7 mg/dl .This is
1. Is an adverse drug reaction
2. Is not an adverse drug reaction
3. Is an adverse drug reaction but reporting not required
4. Is an adverse drug reaction and should be reported
Is an adverse drug reaction and should be reported

33. MCQs –Competitive questions

34. • National Pharmacovigilance programme
initiated in the year [ AIPG –CET 2014]
• 2010
• 2011
• 2014
• 2015
2010

35. Ideally , adverse drug reaction should be
reported
• Within 7 days
• Within 3 days
• Within 2 days
• Within 24 hours
Within 24 hours

36. • Causality assessment can be done using
• Hartwig scale
• Modified thompson scale
• Naranjo scale
• Thompson scale
Naranjo scale

37. • Adverse effects of a drug can be prevented by
improving drug
• Sensitivity
• Specificity
• Efficacy
• Potency
Specificity