This document discusses adverse drug effects and their classification. It defines an adverse drug reaction and describes various types including predictable, unpredictable, chronic, and delayed reactions. It outlines the severity of reactions from minor to lethal. Adverse drug effects are also categorized including side effects, toxicity, intolerance, idiosyncrasy, allergy, photosensitivity, dependence, withdrawal, teratogenicity, mutagenicity, carcinogenicity, and drug-induced diseases. The document provides examples and mechanisms for different types of reactions and discusses prevention of adverse drug effects.

1. ADVERSE DRUG
EFFECTS
AND IT’S CLASSIFICATION
Presented By :- SharonVijayanand
Bachelor of Pharmacy
C.L.Baid Metha College of Pharmacy

2. CONTENTS
DEFINITION
TYPES
SEVERITY
CATEGORIES
PREVENTION

3. DEFINITION
■ An adverse drug reaction is defined as,
“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. TYPES
Predictable-(‘TypeA’ or ‘Augmented
Reaction’)
■ Related to the main pharmacological action of the
drug .
■ Dose dependant and predictable .
■ Example ; - postural hypotension with α1 adrenergic
adrenoreceptor antagonist (α-Blockers).
- bleeding with anticoagulants like warfarin
- sedation with anxiolytics.

5. TYPES
Unpredictable-(‘Type B’ or ‘Bizarre
Reaction’)
■ Idiosyncratic reaction – an abnormal physical
reaction by an individual to a food or drug .
■ Different from the pharmacological action of the
drug .
■ Example :- - aplastic anaemia from
chloramphenicol.
- anaphylaxis in response to penicillin .
• Based on peculiarities of the patient and not on the
drug’s known action. (genetic history)
• Induces an immune response (immune-mediated
toxicity).

6. TYPES
Type C – Chronic Reaction
■ Results from chronic use of the drug .
■ Well known and accepted
■ Eg; tardive dyskinesia with prolonged use of
antipsychotics.
■ Eg; analgesic nephropathy with analgesics.

7. TYPES
TYPE D – Delayed reactions
■ Delayed adr of drugs
■ Refers to teratogenicity and carcinogenicity .
■ Carcinogenic ; drugs which may cause cancer
(diethylstilboestrol - reduce the risk of pregnancy
complications but found to cause clear cell
carcinoma, a rare vaginal tumour)
■ Teratogenic ; drug induced birth defects
(thalidomide – phocomelia ; phenytoin – foetal
hydantoin syndrome)

8. TYPES
TYPE E – End of treatment
■ Withdrawal symptoms/ effect
■ Eg; β blockers used in the treatment of hypertension
and slows down the HR , abrupt discontinuation of
drug will cause rebound hypertension and tachycardia
respectively .
■ Withdrawal of drug should be slow .

9. SEVERITY
■ MINOR :- no therapy, antidote or prolongation of
hospitalization is required.
■ MODERATE :- requires changes in drug therapy,
specific treatment or prolongs hospital stay by at
least one day .
■ SEVERE :- potentially life threatening, causes
permanent damage or requires intensive medical
treatment.
■ LETHAL :- directly or indirectly contributes to death
of the patient.

10. CATEGORIES
adverse drug reactions may be categorised into ;
 Side effects
 Secondary effects
 Toxic effects and
poisoning
 Intolerance
 Idiosyncrasy
 Drug allergy
 Photosensitivity
 Drug dependence
 Drug withdrawal
reactions
 Teratogenicity
 Mutagenicity and
carcinogenicity
 Drug induced
diseases

11. 1. SIDE EFFECTS
■ Unwanted but often unavoidable
pharmacodynamics effect at therapeutic
doses.
■ Not serious.
■ Reduction in dose reduces the symptoms.
■ Further classified as follows ,

12. Side effect based on same action as
therapeutic effect
■ Ex : Atropine –
anticholinergic drug used as
preanaesthetic for its anti
secretory effect – produces
dryness of mouth as side
effect.
■ Ex : Glyceryl trinitrate –
dilates the peripheral
vasculature and relieves
angina –produces postural
hypotension and throbbing
headache as side effect.

13. Side effect based on different facet of
action
■ Ex : Promethazine –
antiallergic drug –
produces sedation as
a side effect which is
unrelated to the
therapeutic action of
the drug .
■ Ex : Estrogens –
antiovulatory action –
cause nausea as a
side effect .

14. An effect may be therapeutic in one
context but side effect in another
context
■ Ex : Codeine –drug
used in the treatment
of cough –produces
constipation as side
effect , the later
being used as
therapeutic effect in
traveller's diarrhoea

15. Many drugs have been developed from
observation of side effects
■ Ex : Sulphonamides –
antibacterial drug –
produces hypoglycaemia
and acidosis as side effect
–directed research
resulting in the
development of
hypoglycaemic
sulfonylureas and carbonic
anhydrase inhibitor –
acetazolamide

16. 2. SECONDARY EFFECTS
■ Indirect consequence of a
primary action of the
drug.
■ Ex :Tetracycline –
antibiotic –causes
suppression of bacterial
flora and paves the way
for super infection.

17. 3. TOXIC EFFECT
 Result of excessive pharmacological
action of drug due to over dosage or
prolonged use.
 over dosage –absolute (accidental,
homicidal, suicidal)
–relative (relating to some
other cause .Ex : usual dose of gentamicin
in presence of renal failure.)
 Manifestations are often predictable
and dose related .
• Organs commonly
involved in drug
toxicity are,
• CNS
• CVS
• Kidney
• Liver
• Lungs
• Skin
• Blood forming organs

18. 3. TOXIC EFFECT
■ Result from ,
■ Functional alteration. Ex : high
dose of atropine –delirium
■ Drug induced tissue damage. Ex:
hepatic necrosis from paracetamol
over dosage.
■ Extension of the therapeutic effect
itself. Ex: coma by barbiturates,
bleeding due to heparin.
■ A different action of the drug. Ex:
morphine –respiratory failure.

19. 4. INTOLERANCE
■ Inability of an individual to
tolerate the adverse effect of a
medication, generally at
therapeutic doses .
■ Converse of tolerance and
indicative of a low threshold of
an individual to the action of the
drug.
■ Ex:Triflupromazine
(antipsychotic) -single dose
induces muscular dystonia.
Ex: few doses of Carbamazepine
(antiepileptic) may cause ataxia.

20. 5. IDIOSYNCRCY
■ Genetically determined abnormal reaction to a
chemical.
■ Drug interacts with some unique feature of the
individual (not found in majority of the subjects) and
produces uncharacteristic reaction.
■ The type of reaction is restricted to individuals with a
particular genotype.
■ Ex: Barbiturates cause excitement and mental
confusion in certain individuals
■ Ex: Chloramphenicol causes non dose related
aplastic anaemia in rare individuals.

21. 6. DRUG ALLERGY /
HYPERSENSITIVITY
■ Abnormal reaction of the
immune system to a
drug .
■ Occur with much smaller
doses.
■ Organs affected: skin,
airways, blood vessel,
blood and GIT .
■ Drug/metabolite -act as
antigen(AG)/Hapten
(incomplete antigen).
■ Drugs have small
molecules which become
antigenic only after
binding with an
endogenous protein and
induce production of
antibody(AB) /sensitized
lymphocytes.

22. MECHANISM ANDTYPES OF DRUG ALLERGY
A. HUMORAL
■ Mediated by
macromolecules found
in the extracellular fluid
(secreted AB,
complement proteins
and certain
antimicrobial peptides.
■ Types ,
■ Type 1 (anaphylactic
reaction)
■ Type 2 (cytolytic)
■ Type 3 (retarded
arthus reactions)

23. MECHANISM ANDTYPES OF DRUG ALLERGY
A. HUMORAL
TYPE 1 (anaphylactic reactions)
■ On exposure to drug, AG:AB
reaction on mast cell surface occurs.
■ Causing the release of mediators
(histamines, 5-HT, LT, PG, PAF).
■ Result in ; urticaria, itching,
angioedema, bronchospasm, rhinitis
and anaphylactic shock.
■ Treatment : antihistamines are
beneficial.

24. MECHANISM ANDTYPES OF DRUG ALLERGY
A. HUMORAL
TYPE 2 (Cytolytic reactions)
• Drug + component of a specific
tissue cell act as AG.
• Result in release of AB (IgG, IgM)
• Binds to target cells andAG:AB
reaction occurs on the surface of
these cells.
• Complement is activated and
cytolysis occurs.
• Ex: thrombocytopenia,
agranulocytosis, aplastic anaemia,
haemolysis, organ damage (liver,
kidney, muscle.),

26. MECHANISM ANDTYPES OF DRUG ALLERGY
A. HUMORAL
TYPE 3 (RetardedArthus Reaction)
• Local vasculitis associated with
deposition of immune complex and
activation of complement system.
• Mediated by circulatingAB (IgG).
• AG:AB complex bind, complement
and precipitate on vascular
endothelium –destructive
inflammatory response.
• Manifestations –rashes, serum
sickness/fever, arthralgia,
lymphadenopathy, poly arteritis
nodosa, Steven-Johnson syndrome
etc.

28. MECHANISM ANDTYPES OF DRUG ALLERGY
B. CELL MEDIATED
TYPE 4 (Delayed
Hypersensitivity Reactions)
• Mediated through the
production ofT-lymphocytes.
• TheT-cells carry receptors for
AG
• AG-binds to receptor –
production of lymphokines –
attract granulocytes-
inflammatory response (such
as contact dermatitis, rashes,
fever, photosensitivity).

29. TREATMENT FOR DRUG ALLERGY
■ Drug causing allergy must be withdrawn.
■ Antihistamine administered forType 1 reactions.
■ For anaphylactic shock and angioedema ,
- put patient in reclining position –administer
oxygen –performCPR if required.
- inject adrenaline, H1 antihistamines , IV
glucocorticoids
• For type 2, type 3, and type 4 reactions administer
glucocorticoids.

30. 7. PHOTOSENSITIVITY
■ Cutaneous reaction resulting from drug
induced sensitization of the skin to UV
radiation.
Types
a) Phototoxic
b)Photo allergic

31. 7. PHOTOSENSITIVITY
a). Phototoxic
■ Drug /metabolite accumulates in
skin , absorbs light and
undergoes photochemical
reaction followed by photo
biological reaction , resulting in
local tissue damage (sun burn
like)
■ i.e. erythema(redness of skin),
oedema, blistering
■ Fast onset and short duration.
■ Followed by hyperpigmentation
and desquamation.
■ Shorter wavelengths are
responsible (290 - 320 nm , UV-B
).
■ Drugs involved in acute
reactions- tetracycline
(demeclocycline) and tar
products.
■ Drugs causing chronic reactions
– halidixic acid ,
fluoroquinolones, dapsone etc.
■ Phototoxic reactions are more
common than photoallergic
recations.

32. 7. PHOTOSENSITIVITY
b). Photoallergic
■ Drug/ metabolite induces a
cell mediated immune
response.
■ Light of longer wavelength is
responsible (320- 400 nm UV-
A)
■ Produces papular,
eczematous contact
dermatitis.
■ May persist long after
exposure and withdrawal of
light source.
■ Rarely antibodies mediate
causing flare, itching, wheal
on exposure to sun.
■ Small doses trigger
reactions.
■ Drugs involved are
sulphonamides,
griseofulvin, chloroquine,
carbamazepine.

33. 8. DRUG DEPENDANCE
■ Physical condition in which the body has adapted to
the presence of a drug.
■ If an individual with drug dependence stops taking that
drug suddenly that person will experience predictable
and measurable symptoms known as ‘withdrawal
syndrome’.
Different aspects of drug dependence includes
 Psychological dependence
 Physical dependence
 Drug abuse
 Drug addiction
 Drug habituation

34. 8. DRUG DEPENDANCE
■ Psychological dependence; individual believes that the
optimal state of well being is achieved only through the action
of the drug. (Ex; opioid, cocaine).
■ Physical dependence; altered physiological state produced by
repeated action of drug causing continuous use of drug to
maintain physiological equilibrium. (Ex: opioids, barbiturates
and other CNS depressants).
■ Drug abuse: use of drug by self medication in a manner not
approved medically (continuous/ occasional).(Ex: opioids ,
cocaine, amphetamine.)
■ Drug addiction: uncontrollable overwhelming need to use a
drug, this compulsion is long lasting – relapse unexpectedly
after period of improvement.(Ex: amphetamine, cannabis)
■ Drug habituation: denotes less intense involvement with drug,
withdrawal produces only mild discomfort. (Ex: tea, coffee ,
tobacco, social drinking.)

35. 9. DRUGWITHDRAWAL
■ Sudden interruption in drug therapy/use result in
adverse consequences mostly in form of worsening
of clinical condition for which the drug was used.
■ Ex: frequency of seizures may increase on sudden
withdrawal of antiepileptic drugs.
■ Ex: severe hypertension, restlessness and
sympathetic over activity may occur shortly after
discontinuing clonidine (antihypertensive drug).

36. 10. TERATOGENICITY
■ Capacity of a drug to cause foetal
abnormality when administered to the
pregnant women .
■ The placenta does not constitute an
effective barrier and drugs are capable
of crossing it.
■ Ex: thalidomide causes phocomelia
(seal like limbs) and other defects .
■ Ex: androgens, progestin cause
masculization of female foetus .

37. 10. TERATOGENICITY
Drugs can affect foetus in 3 stages
 Fertilization and implantation (unto 17 days)-failure
of pregnancy
 Organogenesis (18-55 days)-increased deformities
 Growth and development (56th day onward)-
developmental and functional abnormalities.
It is wise to avoid all drugs during pregnancy unless
strong reasons exist for their use .

38. 11. MUTAGENICITY AND CARCINOGENICITY
■ Capacity of a drug to genetic defects and cancer
respectively.
■ Mutagenicity:- oxidation of drug results in
production of reactive intermediates-affects genes-
structural changes in chromosome –modified to
induce mutation- inherited.
■ Carcinogenicity:- if the modified DNA sequences
code for factors that regulate cell growth/
proliferation (proto oncogenes) – it causes tumour.
■ Anticancer drugs, radio isotopes , oestrogens,
tobacco are carcinogenic.

39. 12. DRUG INDUCED
DISEASES
■ Iatrogenic (Physician induced) diseases.
■ Functional disturbances caused by drugs which
persist even after the offending drug has been
withdrawn.
■ Ex:- peptic ulcer by salicylates and corticosteroids.
■ Ex;- parkinsonism by phenothiazine and other
antipsychotic drugs.
■ Ex:- hepatitis by isoniazid.

40. PREVENTION
■ Avoid inappropriate drug use.
■ Use appropriate dose, route and frequency.
■ Consider previous history of drug reactions.
■ Elicit history of allergic reactions.
■ Rule out the possibilities of drug interactions(when
more than one drug is given).
■ Adopt correct drug administration technique(Ex;- IV
for vancomycin must be slow).
■ Carry out appropriate lab monitoring (Ex;-
prothrombin time with warfarin, serum level of
lithium).

41. THANKYOU