ADR Classification and types

1. Adverse drug reaction
Dr Manjula M J
MD Pharmacology
Senior resident
Dept of Pharmacology
HIMS,Hassan

2. Contents :
• Introduction
• Definition
• Classification
• Types of ADR
• Type A
• Type B – Types of Hypersensitivity reactions
• Type C, D ,E , F

3. Is it the
medications that I
am taking that
are making me
feel sick
Or is it the
symptoms of
the disease ?

4. ADVERSE DRUG REACTION
ADVERSE DRUG REACTION
“Any response to a drug that is noxious and unintended and that
occurs at doses used in man for prophylaxis, diagnosis or
therapy”(WHO)
ADVERSE DRUG EVENT
“Any untoward medical occurrence that may present during
treatment with a medicine , but which does not necessarily have a casual
relationship with treatment”

5. PHARMACOVIGILANCE
Study of adverse drug reactions – Reporting , Assess, Analyse, Manage

6. Classification of ADRs
• Onset of event:
Acute (<60 minutes)
Sub-acute (1-24 hrs)
Latent (>2 days)
• Severity:
Minor, Moderate, Severe, Lethal ADRs

7. • Mild 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.
Classification of ADRs :Depending on Severity

8. • Type A : Augmented pharmacologic effects (Predictable reaction)
• Type B : Bizarre effect (Unpredictable reaction)
• Type C : Chronic effects
• Type D : Delayed effects
• Type E : End of treatment effects
• Type F : Failure(Therapeutic failure)
Types of ADR

9. Type A (Augmented) Type B (Bizarre)
Due to extension of pharmacological action Immunological/genetic basis
Predictable Mostly not predicated
Quantitative(Dose dependent) Qualitative (dose independent )
High incidence but low mortality Low incidence but high mortality
Dose reduction is needed Drugs has to be discontinued
Examples :
• Dryness and blurring of vision due to Atropine
• Hypoglycaemia with Insulin / Glipizide(Oral
hypoglycaemic drug)
• Diarrhoea due to Ampicillin
• Paracetamol – N Acetyl cysteine - Hepatotoxicity
Example :
• Anaphylactic reaction due to Penicillin G (Do sensitivity
test to avoid it)
• Haemolysis with Primaquine
• Succinylcholine apnoea
Types of ADR conti….

10. Types of Allergic reaction :
Type I Type II Type III Type IV
Immediate
Acute Hypersensitivity
Anaphylactic
Reaction
Cytotoxic
Immune Complex
Mediated
Delayed Hypersensitivity
Cell medicated
Tissue sensitive antibodies
IgE
Ex., Anaphylactic reaction
Antigen – Antibody reaction
Ex., Haemolysis by Quinine
Lead / Snake venom
Complement mediated
Serum sickness by Phenytoin
, Penicillin
T-Cell mediated
2-3 days after exposure
Contact dermatitis
Adrenaline 0.3-0.5 ml of 1:1000 i.m/ s.c
Hydrocortisone 100mg every 6hrs
Chlorpheniramine 10-20mg i.v
Hypotension – i.v fluid management

11. Type A

12. • Type a example
Type B

13. Type C Type D Type E Type F
Adverse effects that only occur
remote from treatment and not
with single dose.
Adverse effects that occur
remote from treatment either
in children of treated patients
or in patients themselves;
years after treatment
Adverse effects that occur
when a drug is stopped.
Especially when it is stopped
suddenly (so called withdrawal
effects)
Therapeutic failure
• Drug dependence :
Morphine( Opioid ),
Phenobarbitone
• Organ damage : NSAIDs –
Nephrotoxicity
• Immunosuppression –
Steroids
• Retinal and corneal
deposits – Chloroquine
• Craniofacial malformations
in infants whose mothers
have taken Isotretionoin
• Fetal hydantoin syndrome –
Phenytoin
• Beta blockers – Ex.,
Atenolol worsening of
Angina
• Coticosteroids – Adrenal
insufficiency
• Failure of Vaccines
• Failure of Oral
contraceptives

14. • pictures
Nephrotoxicity - NSAIDs

15. ADR - Other than allergic reaction :
GIT Nausea , Vomiting (Cytotoxic drugs, Levodopa)
Diarrhoea(Ampicillin, Tetracycline)
Constipation (Morphine, Codeine)
Mucosal erosion and Gastritis (NSAIDs)
Haematopoietic Cytotoxic drugs – Bone marrow depression,
Chloramphenicol
Organ toxicity :
a) Hepatotoxicity
b) Nephrotoxicity
c) Cardiotoxicity
d) Pulmonary
e) Visual disturbance
f) Ototoxicity
g) CNS
h) Neurological
i) Endocrine / Infertility
j) Dermatological
k) Electrolyte imbalance
l) Altered taste
m) Susceptibility to infection
n) Weight gain
Rifampicin, Isoniazide, Halothane, Sodium valproate
Aminoglycosides, Vancomycin, Cefotaxime
Tetracyclic antidepressants, Doxorubicin, Digoxin
Bleomycin, Busulfan
Sildenafil, Voriconazole
Aminoglycosides(Gentamycin), Salicylates Minocycline
Neroleptics(Chlorpromazine), Levodopa, Alcohol
Isoniazide, Quinine
Spiranolactone ,Chlorpromazine
Alopecia due to Anticancer drug
Diuretics
ACE inhibitors
Steriods
Antidepressants

16. Factors causing ADR
• Patient factor : Age, Genetic constitution, Environmental hazard,
Allergy, Polypharmacy, Over the counter drug
• Drug factor : Look alike, Sound alike, Route of administration,
Sterilization, Excipient
• Blood transfusion
• Cosmetic usage
• Clinician /prescriber factor : Inappropriate, Abrupt discontinuation,
Prescribing unsafe drugs during pregnancy
• Nursing factor
• Medical devices/instruments

17. Clinical significance of ADR
• Drug induced diseases
• Hospital admissions due to ADR 3-5%
• ADR increases the duration of hospital stay
• Most ADRs are reversible Ex., Ethambutol – Visual disturbance
Isoniazid – Hepatotoxicity Chloramphenicol – Bonemarrow depression
• Specific side effects – Differentiate - due to drug or new symptoms
• Surgeries could be avoided

18. ADR monitoring :
Pharmacovigilance :
“Pharmakon : Drug” and “Vigilance : to keep watch or alert”
WHO defines pharmacovigilance as the science and activities relating to
the detection, assessment, understanding and prevention of adverse
effects of marketed medicines or those under trial.

19. Reporting ADR
• Subjective : Patient complains – Patient, Pharmaceutical companies
reports
• Objective : Direct observation – Medical faculties
- Abnormal systemic finding
- Lab tests
- Histology

20. Drug history :
• Can cause the disease :
Ex., Aspirin – Asthma ,Glucocorticoids – Diabetes
• Can cause toxicity or loss of effect
• Drugs can affect the diagnosis
• Can help in deciding the choice of drug

21. Prevention of ADR
• Use drugs rationally
• Drug history and history of drug allergy
• Drug interaction
• Signs of overdose / toxicity
• Therapeutic drug monitoring
• Assess risk-benefit ratio
• Adequate information should be given to the patient

22. ADR - Summary
ADR / ADE Types of ADR Classification Types of Allergic
reaction
“Any response to a drug that is
noxious and unintended and that
occurs at doses used in man for
prophylaxis, diagnosis or
therapy”(WHO)
“Any untoward medical
occurrence that may present
during treatment with a
medicine , but which does not
necessarily have a casual
relationship with treatment”
Type A
Type B
Type C
Type D
Type E
Type F
Onset of events
Severity
Type 1
Type 2
Type 3
Type 4
-Factors affecting ADR
-Clinical significance
-Monitoring of ADR
-Importance of Drug
history
-Prevention of ADR