ADVERSE DRUG
REACTIONS
(ADR)
COURSE: PHA 301
COURSE TITLE: GENERAL PRINCIPLES OF
PHARMACOLOGY
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACEUTICAL SCIENCES,
DAVID UMAHI FEDERAL UNIVERSITY OF HEALTH SCIENCES, UBURU
Definition of adverse drug reaction
According to WHO,
An adverse drug reaction (ADR) is a response to a drug which is noxious
and unintended and which occurs at doses normally used in man for the
prophylaxis, diagnosis, or therapy of disease or for the modification of
physiological function.
CLASSIFICATIONS OF ADR (Rawlins-
Thompson)
A (Augmented)
B (Bizarre)
C (Continuous)
D (Delayed)
E (End of use)
F (Failure of efficacy)
Broadly
Type- A (Predictable)- Based on pharmacological properties
Type- B (Non-predictable) – Based on Immunological response and genetic
TYPE A- AUGMENTED
These are based on the pharmacological properties of the drug, hence, it can be predicted.
Dose related, preventable, common and mostly reversible.
It includes: Side effects, secondary effects and toxic effects
Examples:
Hypotension - Anti-hypertensives (e.g. Αlpha-1-antagonists)
Hypoglycemia - Anti-diabetics (e.g. sulfonylureas)
Action taken by medical practitioner
Adjust the dose
Not to give concomitant drugs with the same mechanism of action
SIDE EFFECTS
Undesirable often unavoidable pharmacodynamic effects at therapeutic doses and
predictable
Examples: Benzodiazepines- Motor in-coordination
H1 Anti-histaminics- Sedation
Glycerol trinitrate relieves angina pectoris but produces postural hypotension
An effect may be therapeutic in one context but side effect in another context.
Example: Constipation by codeine is side effect but can be used as therapeutic effect in
patient with loose motions.
SECONDARY EFFECTS
Indirect consequences of a primary action of the drug.
Examples:
Corticosteroids causes immunosuppression and thus activates latent tuberculosis.
Tetracycline is a broad spectrum antibiotics and can lead to superinfection.
TOXIC EFFECTS
The effects are predictable and results from over dose or prolonged use resulting in
exaggerated pharmacological effects of the drug.
Examples:
High doses of heparin causes bleeding
Barbiturates causes coma and respiratory depression at high dose
Morphine overdose causes respiratory failure
TYPE B- BIZZARE
They are not predicted from the pharmacology of the drug. Not dose dependent and
results from patients response to a drug.
They develop on the basis of immunological reaction on a drug (Allergy) and genetic
predisposition (Idiosyncratic reactions)
It includes: Intolerance, Hypersensitivity/allergy and Idiosyncracy
Example: Hypersensitivity to penicillin and sulphonamides
Action taken by medical practitioner:
Immediate withdrawal of the drug.
Avoid use of the drug in the future.
Instruct the patient to report themselves to any practitioner they may consult in the
INTOLERANCE
Intolerance is the appearance of characteristic toxic effects of a drug in an individual at
therapeutic doses.
It indicates a low threshold of the individual to the action of a drug.
Examples:
Only few doses of carbamazepine may cause ataxia in some patients.
One tablet of chloroquine can cause vomiting and abdominal pain in some patients
Tinnitus after a single oral dose of aspirin.
TYPES OF ALLERGIC REACTIONS
A) HUMORAL
Type I/ anaphylactic reactions: immediate onset of hypersensitivity reaction within
minutes. Potentially life threatening. E.g. Penicillin induces anaphylaxis and urticaria
Type-II / cytolytic reactions: Antibody mediated. E.g. Qunidine can cause haemolytic
anaemia and thrombocytopenia.
Type-Ill / Immune complex: precipitate in tissues and induce inflammatory response.
E.g. Omalizumab is associated with Serum Sickness like reaction (SSLR).
B) CELL MEDIATED
Type-IV (delayed hypersensitivity) reactions: T-cell mediated and takes 12 hrs to
occur.
PHOTOSENSITIVITY
It is as a result of hypersensitivity to sunlight.
It is a cutaneous reaction resulting from drug induced sensitization of the skin to UV
radiation.
The reactions are of two types:
Photo-toxic: Drug or its metabolite accumulates in the skin causing tissue damage
(sunburn-like), i.e. erythema, edema, blistering , hyper pigmentation, desquamation.
Drugs include: tetracycline, doxycycline, amiodarone, piroxicam, hydrochlorothiazide.
Photo-allergic: Drug or its metabolites induce a cell mediated immune response which
on exposure to light, produces a papular or eczematous contact dermatitis like picture.
IDIOSYNCRASY
It is a genetically determined abnormal reactivity to a chemical.
The drug interacts with some unique feature of the individual, not found in majority of
subjects, and produces the uncharacteristic reaction.
Examples:
Chloramphenicol produces non dose-related serious aplastic anaemia in rare individuals.
Barbiturates cause excitement and mental confusion in some individuals.
Quinidine causes cramp, diarrhea, asthma and vascular collapse in some individuals.
TYPE C – CHRONIC (CONTINOUS)
USE
They are mostly associated with cumulative-long term exposure
Related to the cumulative dose and time.
Examples:
Analgesic (NSAID)– interstitial nephritis
Omeprazole – osteoporosis, gynecomastia.
Corticosteroids cause hypothalamic-pituitary-adrenal axis supression
Action taken by medical practitioner
Use the lowest dose for shortest duration
Alternate day therapy
TYPE D – DELAYED
They manifest themselves with significant delay after many years of
treatment.
It includes teratogenicity and carcinogenicity
Examples:
Teratogenesis: Flipper-like fore limbs - Thalidomide
Carcinogenicity - bladder carcinoma after treatment with
cyclophosphamide
Action taken by medical practitioner
TERATOGENICITY
Teratogenicity is foetal abnormalities produced by some drugs when administered to
pregnant women.
Examples: ACE inhibitors, Thalidomide, Warfarin, Barbiturates etc.
Carcinogenicity: Genetic defects and cancer caused by the drug.
Even without interacting directly with DNA, certain chemicals can promote malignant
change in genetically damaged cells, resulting in carcinogenesis.
Example: Cyclophosphamide
TYPE E – END OF USE
These reactions occurs at the end of the dose or the drug is stopped or after sudden
drug withdrawal.
Examples:
Sudden withdrawal of long term therapy with alpha-blockers can induce rebound
tachycardia and hypertension
Frequency of seizures after sudden withdrawal of phenytoin
Opioid withdrawal reactions
Action taken by medical practitioner
Taper the drug slowly
Give concomitant drug which has antagonistic action
TYPE F
Ineffectiveness is often caused by drug interactions
Examples:
Failure of oral contraceptives in the presence of enzyme inducers like phenytoin, rifampin etc.
Acute adrenal insufficiency may be precipitated by abrupt cessation of corticosteroid therapy.
Action taken by the health care practitioner
If more than two than drugs taken, check if there are drugs that interact with major drugs
prescribed; amoxicillin can reduce the plasma concentration of ethinyl estradiol
Check for cytochrome P450 enzyme inducers capable of reducing the plasma concentration of
the other drug.
Dose Increase
CLASSIFICATION OF ADR (BASED ON
SEVERITY)
Minor: No therapy, antidote or prolongation of
hospitalization is required.
Moderate: Requires change in drug therapy, specific
treatment or prolongs hospital stay.
Severe: Potentially life-threatening, causes permanent
damage or requires intensive medical treatment.
Lethal: Directly or indirectly contributes to death of the
CLASSIFICATION OF ADRs (Basis of
Onset)
Acute: Observed within 60 minutes e.g. anaphylactic shock, bronchoconstriction, nausea
& vomiting
Sub acute: Observed within 1-24hours (within one day) e.g. maculopapular rashes, serum
sickness, allergic vasculitis & antibiotic associated diarrhea
Latent: More than two days e.g. organ toxicity, dyskinesia due to use of antipsychotic
drugs.
PREVENTION OF ADVERSE EFFECTS TO DRUGS
Avoid inappropriate use of drugs.
Appropriate drug administration: Dose, dosage form, duration, route, frequency,
technique.
Ask for previous history of drug reactions and allergies.
Always suspect ADR when new symptom arises after initiation of treatment.
Ask for laboratory findings like serum creatinine etc.
DRUG INDUCED DISEASES
These are also called iatrogenic (physician induced) diseases, and are functional
disturbances (disease) caused by drugs .
Examples:
Hepatitis by isoniazid and Rifampicin
Peptic ulcer by salicylates and corticosteroids
Retinal damage by chloroquine
