Different types of adverse drug reactions

1. Dr. Aravinda Kumar. B
Assistant Professor
Department of
Pharmacology,
PIMS.

2. Adverse drug event (ADE):
• Any untoward medical occurrence that may present
during treatment with a medicine, but which does not
necessarily have a causal relationship with the
treatment.

3. What is an 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 the future use of the
same drug.

4. SEVERITY OF ADRs
• Minor – no therapy, antidote or prolongation of hospitalization
is required
• Moderate – requires change in drug therapy, specific treatment
or prolongs hospital stay by atleast one day
• Severe – potentially life-threatening, causes permanent
damage or requires intensive medical treatment
• Lethal – directly or indirectly contributes to death of the patient

5. FACTORS CAUSING ADRS
• PATIENT FACTORS – age, sex, genetics,
• DRUG FACTORS – type A or B reaction
• CLINICIAN/PRESCRIBER FACTOR – duration of treatment,
when to discontinue, which drug to be prescribed in pregnancy,

6. MANIFESTATIONS OF ADRs
• GIT – nausea, vomiting, constipation, diarrhea, gastric mucosal
erosion & ulceration with bleeding
• HEMATOPOIETIC – bone marrow depression
• ORGAN TOXICITIES – hepatotoxicity, nephrotoxicity, cardiac
toxicity, ototoxicity, ocular toxicity, CNS toxicity, endocrine & infertility,
dermatological toxicity
• OTHERS – mask taste & smell.

7. TYPES OF ADVERSE DRUG
REACTIONS
• Type A (augmented/predictable)
• Type B (bizarre/non-predictable)
• Type C (chronic use)
• Type D (delayed effect)
• Type E (end of use/abrupt withdrawal)
• Others

8. Type A Type B Type C Type D Type E Others
Side effects Allergic
reactions
Drug
dependence
Teratogenicity Withdrawal
reactions
Iatrogenic
Secondary
effects
Idiosyncrasy Cumulative
toxicity
Mutagenicity Photosensitive
reactions
Toxic effects Organ damage Carcinogenicity Masking of
diseases
Poisoning Immuno
suppression
Exacerbation
of disease
Intolerance

9. Type A (augmented) Type B (bizarre)
• Due to extension of
pharmacological action
• Immunological/ genetic basis
• Predictable • Mostly not predictable
• Quantitative (dose dependent) • Qualitative (dose dependent)
• High incidence but low mortality • Low incidence but high mortality
• Dose reduction is needed • Drugs has to be discontinued
• Examples: dryness of mouth &
blurring of vision due to
atropine; hypoglycemia with
glibenclamide
• Anaphylactic reaction due to
penicillin G; hemolysis with
primaquine

10. Type A reactions
• Side effect
• Toxic effect and drug toxicity or poisoning
• Secondary effect
• Intolerance

11. SIDE EFFECTS
• Unwanted & unavoidable PD effects at therapeutic doses
• It may be same as therapeutic effect (atropine, GTN)
• It may be a different facet of action (promethazine, estrogen)
• May be therapeutic in one context but side effect in another
context (codeine)
• Discovery based on side effects (sulfonamides)

12. SECONDARY EFFECTS
• Indirect consequences of a primary action of a drug
• Examples : suppression of bacterial flora by tetracyclines leads to
superinfections
• Corticosteroids weaken host defence mechanisms so that latent
TB gets activated.

13. TOXIC EFFECTS
• Result from excessive pharmacological action of the drug due to
over dosage (absolute/relative) or prolonged use.
• Manifestations are predictable & dose related
• Functional alteration (atropine), drug induced tissue damage
(paracetamol), extension of therapeutic effect (barbiturates,
heparin), additional action of a drug (morphine, streptomycin)

14. POISONING
• Poisoning - harmful effects of a chemical on biological system
• Result from large doses (it is the dose which distinguishes a drug
from a poison)
• Management protocol

15. INTOLERANCE
• It is the appearance of characteristic toxic effects of a drug in an
individual at therapeutic doses.
• Indicates low threshold of the individual to the action of the drug
• Eg. Chloroquine (vomiting & abdominal pain), triflupromazine
(muscular dystonias), carbamazepine (ataxia)

16. Type B reactions
• Drug allergy / allergic reactions
• Idiosyncratic reactions (pharmacogenomics)

17. IDIOSYNCRASY
• Genetically determined abnormal reaction to a chemical
• total absence or reduced activity of some enzyme ( eg. G6PD
deficiency – primaquine, salicylates, sulfonamides - hemolysis
• Examples: barbiturates (excitement & mental confusion),
chloramphenicol (aplastic anemia)

18. Immunologically mediated reaction producing symptoms which
are unrelated to the pharmacodynamic profile of the drug.

19. TYPES OF ALLERGIC
REACTIONS
• Type 1 (anaphylactic reactions)
• Type 2 (cytolytic reactions)
• Type 3 (arthus reaction)
• Type 4 (delayed hypersensitivity reaction)

20. TYPE 1 TYPE 2
TYPE 3 TYPE 4

21. TYPE C REACTIONS
• Drug dependence
• Organ damage
• Cumulative toxicity
• Immunosuppression

22. DRUG DEPENDENCE
• Drugs for personal satisfaction is accorded a
higher priority than other basic needs, often in
the face of known risks to health.
• Psychological (reinforcement) & physical
dependence
• Drug abuse, addiction & habituation

23. • Psychological – individual believes that optimal
state of well being is achieved only through
action of drug (emotionally distressed if drug is
not taken – compulsive drug use)
• Physical – altered physiological state produced by
repeated administration of a drug, necessitates
continuous presence of drug to maintain
physiological equilibrium (discontinuation –
withdrawal syndrome) – neuroadaptation

24. • Drug abuse – use of a drug by self medication
(deviates from the approved medical and social
pattern) – continuous, occasional
• Drug addiction – compulsive drug use/
overwhelming involvement,
• Drug habituation – less intense involvement with
drug, withdrawal produces only mild discomfort

25. Type D reaction
• Mutagenicity and carcinogenicity
• Teratogenicity

26. MUTAGENICITY &
CARCINOGENICITY
• Drug cause genetic defects and cancer respectively.
• Oxidation of drug - produce reactive intermediates – affect genes
and cause structural changes in chromosomes – covalent
interaction with DNA – induce mutations.

27. TERATOGENICITY
• Fetal abnormalities when given to pregnant mothers
• Affect fetus at 3 stages:
1. Fertilization & implantation – conception to 17days – failure
2. Organogenesis – 18 to 55 days – most vulnerable (deformities)
3. Growth & development – 56 days onwards – developmental &
functional abnormalities.

28. DRUG EFFECT
Thalidomide Phocomelia, heart defects, gut atresia
Warfarin Saddle nose, retarded growth, defects of limbs, eyes and
CNS
Corticosteroids Cleft palate and congenital cataract
Androgens Masculinisation in female
Oestrogens Testicular atrophy in males
Ethanol Fetal alcohol syndrome
Valproate Neural tube defects
Phenytoin Cleft lip/palate, microcephaly, mental retardation
Aminoglycosides Deafness

30. category Examples
A
No risk
Adequate studies in pregnant women have failed
to demonstrate a risk to the fetus
Inj. Magnesium sulfate,
thyroxine
B
No evidence of risk
in humans
Adequate human studies are lacking, but animal
studies have failed to demonstrate a risk to the
fetus
Penicillin, amoxicillin,
erythromycin,
paracetamol
C
Risk cannot be ruled
out
No adequate studies in preg women, & animal
studies are lacking or have shown an adverse
effect on fetus, but potential benefit may warrant
use of drug in preg women despite potential risk
Morphine, atropine,
corticosteroids,
thiopentone, bupivacaine
D
Benefit may out
weigh potential risk
There is evidence of human fetal risk, but the
potential benefits from use of drug may be
acceptable despite the potential risk
Aspirin, phenytoin,
carbamazepine,
valproate, lorazepam
X
Contraindicated
Studies in humans or animals have demonstrated
fetal abnormalities, and potential risk outweighs
possible benefit
Estrogens, isotretinoin,
ergometrine

31. TYPE E (withdrawal
reaction)
• Acute adrenal insufficiency – corticosteroids
• Rebound hypertension – clonidine
• Worsening of angina pectoris – beta blockers
• Seizures - antiepileptics

32. PHOTOSENSITIVITY
• Cutaneous reaction resulting from drug induced
sensitization of the skin to UV radiation
• phototoxic (tetracyclines, nalidixic acid,
fluoroquinolones) - short wavelengths (290-320nm) –
shorter duration after exposure ends
• photoallergic (sulfonamides, sulfonylureas,
chloroquine) – longer wavelengths (320-400nm) –
persist long after exposure – lesion extend beyond
exposed areas.

33. DRUG INDUCED DISEASES
• Peptic ulcer – salicylates, corticosteroids
• Parkinsonism – antipsychotics
• Hepatitis – anti-tubercular drugs

34. PHARMACOVIGILANCE
• “Science and activities relating to the detection,
assessment, understanding and prevention of adverse
effects or any other drug related problems.”
• Usefulness – educate doctors, official regulation of drug
use, reduction in drug-related harm to patients, rationale
use of medicines.

35. Activities involved in pharmacovigilance
• Post marketing surveillance & other methods of ADR
monitoring
• Dissemination of ADR data – drug alerts, medical
letters, advisories sent by FDA
• Changes in labelling of medications

36. Governing bodies of
Pharmacovigilance
• Uppsala Monitoring Committee (Sweden) – international
collaborating centre
• Central Drugs Standard Control Organization (CDSCO) – India
• Assess causality (Naranjo algorithm) and severity (modified
Hartwig scale

38. CAUSALITY
Assessment
• TEMPORAL RELATIONSHIP
• PREVIOUS KNOWLEDGE
• DECHALLENGE
• RECHALLENGE
Grading
• DEFINITE
• PROBABLE
• POSSIBLE
• DOUBTFUL

39. PREVENTION OF ADVERSE
EFFECTS
• Avoid inappropriate use of drugs
• Use appropriate dose, route & frequency of drug administration
• Previous history of drug interactions, allergic diseases
• Rule out drug interactions
• Adopt correct administration technique
• Carry out appropriate laboratory monitoring