This document discusses adverse drug reactions (ADRs), including their definition, frequency, impact on public health, classification, management, and prevention. Some key points: - ADRs are the 4th-6th leading cause of death among hospitalized patients in the US. - They are classified based on factors like onset (acute, subacute, latent), type (augmented, bizarre, continuous), and severity (minor to lethal). - Common causes of ADRs include dosage errors, allergies, drug interactions, and failure to follow dosing regimens. Patient risk factors include age, sex, genetics, and concurrent diseases or medications. - Prevention strategies include proper dosing, screening

1. Dr Manjunath GN
Professor & Head Department of
Pharmacology

2. PH 1.7 - Specific learning objectives
• Define an ADR
• Explain the frequency of ADRs and their impact
on public health
• Describe the common classification of ADRs with
examples
• Describe the management of ADRs.
• Describe the important risk factors that predict
susceptibility to ADRs.
• Explain the importance of monitoring in
prevention of ADRs.

3. Some people are like a Drug.
But they also give you heartbreak, tears and
stress

4. Adverse drug reactions
• 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 for in future use of the same
drug.
Adverse drug event –
• Any untoward medical occurrence that may
present during treatment with medicine , but
which may not have causal relationship with the
treatment.

5. STATISTICS
 Fourth to sixth causes of death in hospitalized
patients in the US
 3–7% of all hospitalizations
 10–20% of inpatients suffer from drug-
related adverse reactions
 Only 1 in 20 adverse reactions is actually
detected and defined as a real side effect;
this leads to the erroneous assumption that
the incidence of adverse reactions is much
lower than it actually

6. COMMON CAUSES OF ADRS
Failure to maintain correct dosage regimen
Overdosing - accidental
Allergies to chemical components
Consuming drugs when on alcohol.
Drug interactions – same or different systems
Taking a medicine that was prescribed for
someone else.

7. FACTORS AFFECTING ADR:
Drug-related factors
 Dose
 Duration
 Inherent toxicity of the
agent
 Pharmacodynamic
properties
 Pharmacokinetic
properties
Patient-related factors
 Age
 Sex
 Genetic influences
 Concurrent diseases
 Previous adverse drug reactions
 Compliance with dosing
regimen
 Total number of medications
 Misc. (diet, smoking,
environmental
exposure)

8. TYPES BASED ON ONSET
Onset of event:
 Acute - within 60 minutes
 Sub-acute - 1 to 24 hours
 Latent - > 2 days

9. TYPES OF ADR
Type Reaction
Type A Augmented
Type B Bizarre
Type C Continuous
Type D Delayed
Type E End of use
Type F Failure of efficacy

10. SEVERITY OF ADR
Minor Moderate Severe Lethal
No
treatment/
Antidote/
Prolongation
of
hospitalisation
Requires
treatment/
Change in
treatment/
Prolongation
by at least 1
day
Requires
intensive
treatment ,
Life
threatening,
Permanent
damage
Directly/
Indirectly
contributes
to the death
of the
patient

11. Type A (Augmented)
Predictable
Type B (Bizzare)
Unpredictable
Expected- Undesirable Unexpected- Undesirable
Based- Pharmacological
properties of drug
Based- Peculiarities of patient
More common Less common
Dose related Non dose related
Mostly preventable and reversible More serious, requires
drug withdrawl
Includes- Side effects ,
Secondary effects , Toxic
effects, Consequences of drug
withdrawal
Includes-Hypersensitivity/allergy,
Idiosyncrasy
ADR CLASSIFICATION

12. TYPE A REACTIONS OR AUGMENTED
• Pharmacological properties of a drug
Extension effects
 Predictable
 Dose - Related responses
 Prevention - Adjustment of dosage regimen
Examples
 Furosemide -Water and electrolyte imbalance
 Pheniramine - sedation
 Insulin - Hypoglycemia

13. TYPE B REACTIONS OR BIZARRE
Abnormal effects
Unrelated from the
drug’s known
pharmacological
actions
Ex. Hypersensitivity
reactions, Stevens-
Johnson’s Syndrome,
Hemolytic anemia

14. TYPE C OR CONTINUOUS
• Long term effects are
usually related to the dose
and duration of treatment
 Examples
chloroquine -
Retinopathy
NSAIDs -
Nephrotoxicity
TYPE D REACTIONS OR DELAYED
 Carcinogenesis
 Teratogenecity
 Example:
Thalidomide -
phocomelia

15. TYPE E OR END OF USE
• Benzodiazepines – Rebound
insomnia, agitation
• Clonidine – Rebound
hypertension
• Corticosteroids –
Acute adrenal
insufficiency
TYPE F OR FAILURE OF EFFICACY
 Counterfeit medicines
 Underdosing of medications
 Drug interactions

16. ADVERSE DRUG EFFECTS MAY BE CATEGORISED INTO
1. Side Effects - Undesirable effects at
therapeutic doses. e.g
a)Atropine → Pre-anesthetic medication →
(undesirable ) dry mouth
b) Codeine → Suppresses Cough
(desirable)→ Constipation (undesirable)
Making Use of side effects -
• Minoxidil → Antihypertensive → Hypertrichosis
→ Male pattern baldness
• Codeine → used in travelers diarrhea

17. 2.Secondary Effects- Indirect consequence of
primary action of drugExamples -
a)Corticosteroids → ↓Immunity → Latent T.B.
activated
b)Tetracyclines → ↓Bacterial flora → Super-infection.
3. Toxic Effects-Exaggerated form of side effects due to
over dosage/prolonged use. Examples -
a)High dose heparin → Bleeding
b)Prolonged use of streptomycin →Ototoxicity,
nephrotoxicity

18. 4. Allergy/Hypersensitivity-Immunologically mediated
allergic responses occurs when sensitized individuals
are re-exposed to same drug again
 Humoral-Type I,II,III
 Cell mediated-Type IV

19. • Type I - Anaphylactic reactions due toIgE
antibodies, min→2-3 hours. Examples - urticaria,
angioedema , anaphylactic shock
• Type II - Cytolytic reactions due to antigen antibody
complex , within 72 hours. Examples - hemolytic
anemia , SLE.
• Type III – Retarded or Arthus reaction- Immune
complex mediated reactions, 72 hours→1-2
weeks. Examples - serum sickness (fever,
arthralgia, lymphadenopathy),PAN , Steven
Johnson syndrome , procainamide induced
systemic lupus erythematosis.
• Type IV - Delayed hypersensitivity reaction. Examples -
Contact dermatitis

20. 5. Idiosyncrasy - Genetically determined abnormal
reactivity to a chemical. Here drug interacts with some
unique features of individuals , not found in majority of
subjects, produces uncharacteristic reaction
Examples - Barbiturates → excitement and mental
confusion in some patients. Chloramphenicol → Aplastic
anemia in some patients.
6. Drug Intolerance -
- Characteristic toxic effects at therapeutic dose
- Converse of tolerance
- ↑ sensitivity to low doses
Examples - Single dose triflupromazine → muscular
dystonia

21. 7. Photosensitivity - Cutaneous reactions → sensitized skin→
UV radiation.
– Two types:
a) Phototoxicity-Drug/ metabolite accumulates in skin
→ absorbs light → photochemical and
photobiological reaction → local tissue damage i.e.
erythema, edema, blistering, hyperpigmentation.
e.g. Tetracyclines
b) Photoallergy - Drug/metabolite → cell mediated
immune response → UV light → papular or
eczematous contact dermatitis like picture. e.g.
Sulfonamides, Griseofulvin

22. 8. Drug withdrawal reactions -
• Sudden interruption of drug → worsens clinical condition
for which previously drug was used.
• Examples -
a) Corticosteroids → acute adrenal insufficiency
b) Beta Blockers → worsening of angina , precipitates
myocardial infarction

23. 9. Teratogenicity
1)Fertilization &
implantation
(blastocyst
formation)
Conception to 17
days - failure of
pregnancy -
Cytotoxic drugs ,
alcohol .
2) Organogenesis
- 18-55 days of
gestation - most
vulnerable period
- deformities are
produced –
teratogens.
3) Growth and
development -
Developmental &
functional
abnormality
ACE inhibitors -
Hypoplasia of organs
NSAIDS- Premature
closure of ductus
arteriosus
Drug → pregnant mother → fetal abnormalities
1. Thalidomide → Phocomelia.
2. Diethylstilbesterol → Vaginal adenocarcinoma.
3. Valproic acid → Neural tube defects.

24. 10. Carcinogenicity and Mutagenicity (Type c)
Carcinogenicity - Oxidation → reactive
metabolites → structural gene damage
e.g. Anticancer drugs , estrogens
Mutagenicity: Structural changes in DNA 
Oxidation of the drugs produces reactive
metabolites  Covalent interaction with DNA
e.g Anti cancer drugs, radioisotopes

25. 11. Iatrogenic (Physician induced diseases)- Examples -
a) NSAID'S → Peptic ulcers
b) Hydralazine → DLE
c) Phenothiazines → Parkinsonism
d) INH → Hepatitis
12. Drug Dependence- Use of drug produces a state in which
person believes that continuous use is necessary for state of
well being or to avoid withdrawal symptoms
– Psychic dependence Here person believes that state of wellbeing
achieved only with action of drugs. Opioids , Benzodiazepines
– Physical dependence Here repeated administration of drug required
to maintain physiological equilibrium. Discontinuation → withdrawal
Alcohol , Barbiturates , Benzodiazepines

26. PREVENTION OF ADR
1. Avoid all inappropriate use of drugs.
2. Use of appropriate dose, route & frequency of drug
administration.
3. Elicit & take into consideration previous history of
drug reactions.
4. Elicit h/o allergic diseases & exercise caution.
5. Rule out possibility of drug interaction.
6. Adopt correct drug administration technique.
7. Carry out appropriate laboratory investigation.
8. Be aware of interactions with certain foods,
alcohol and even with household chemicals.

27. MANAGEMENT OF ADR
• Discontinue the offending agent if -
 It can be safely stopped
 The event is life-threatening or intolerable
 There is a reasonable alternative
 Continuing the medication will further exacerbate
the patient’s condition
• Continue the medication (modified as needed) if-
 It is medically necessary
 There is no reasonable alternative
 The problem is mild and will resolve with time

28.  Discontinue non-essential medications
 Administer appropriate treatment -
• e.g., atropine, protamine sulfate ,digibind
antibodies, flumazenil.
 Provide supportive or palliative care -
• e.g., hydration, glucocorticoids, warm / cold
compresses, analgesics or antipruritics
 Consider re-challenge or desensitization

29. MANAGEMENT OF POISONING
A. Maintain vital & physiological functions from
impairment
B. Termination of exposure (decontamination)
C. Prevention of absorption of ingested
poison.(activated charcoal)
D. Hastening elimination
1. Urinary alkanlization
2. Multidose activated charcoal
3. Extracorporeal drug removal
E. Antidote therapy

30. PHARMACOVIGILANCE
Definition – Science and activities relating to
the Detection, Assessment, Understanding and
Prevention of adverse effects or any other
drug related problems .

31. Urticaria and rash

32. FDE

33. TEN

34. Angioedema and steven johnson
syndrome

35. Phototoxic and photoallergic