ADVERSE EFFECTS OF DRUGS

Prof. Solomon Sunder Raj M.Pharm, PhD

Head of the Department of Pharmacology
Bharath Institute of Technology, Hyderabad, India
INTRODUCTION
• When a drug is administered to a patient,
essentially two types of reactions can occur,
desired effects and the undesired effects.
• The desired drug effects are those clinically
beneficial actions for which the drug has been
prescribed.
• The undesirable drug effects are those which do
not have those any pharmacological actions.
ADVERSE EFFECT:
Adverse effect is any undesirable unintended
consequence of drug administration. It includes
all kinds of noxious effects

ADVERSE DRUG REACTION(ADR):

An adverse drug reaction is any response to a
drug which is noxious (injurious) and unintended
and which occurs at doses used in man for
prophylaxis, diagnosis or therapy of disease.
Some antihistamines cause
drowsiness and also control
symptoms of allergies.

 When antihistamines are

taken during day time,
drowsiness is an unwanted
effect
 Major adverse drug reactions
• Allergic reactions • Convulsions
• Anaphylactic shock • Hypertension
• Coma • Diabetes mellitus
• Cardiac arrhythmias • Paralysis
• Congestive heart • Kidney or liver
failure dysfunction
 PHARMACODYNAMIC
EFFECTS

DESIRABLE UNDESIRABLE
OR OR
BENEFICIAL EFFECTS ADR

EXPECTED UNEXPECTED
UNDESIRABLE EFFECTS UNDESIRABLE EFFECTS
(TYPE A - ADR) (TYPE B - ADR)
 UNDESIRABLE EFFECTS
EXPECTED UNEXPECTED
UNDESIRABLE UNDESIRABLE
EFFECTS EFFECTS

Hypersensitivity
Side effects
or allergy

Genetically
Secondary effects
determined ADR

Idiosyncratic
Toxicity
responses
SIDE EFFECTS:
 These are observed even with the therapeutic doses of
the drug
 These are usually mild and manageable

Eg: DICYCLOMINE (anti cholinergic drug) – dryness of

mouth
PROMETHAZINE (antihistaminic drug) - sedation
 Secondary effects:
These are indirect consequences of the main
pharmacodynamic action of the drug

Eg: Development of super infection after suppression of

bacterial flora by ANTIBIOTICS
Weakening of host defenses after use of
CORTICOSTEROIDS
 Toxicity:
These are exaggerated form of side effects which
occur due to over doses or after prolonged use of the
drug.

Eg: morphine - respiratory failure in overdose

Imipramine – vestibular damage on prolonged use
 HYPERSENSITIVITY

Hapten + Body protein

Antigen

Mechanism of the allergic

Stimulus for formation
Response:
Of antibodies

After first exposure to the drug

antibody
Hapten + Body
protein Antigen

Antibody

After re-exposure to the same drug Antigen-

antibody
complex

Release
Tissue
allergy of chemical
Or mast
mediators
cells
Drugs may cause following types of allergy:

Type 1 (immediate type):

 Allergy develops within minutes and lasts for 2-3 hrs.

 Antibodies IgE get fixed to the mast cells.
 On exposure to drug AG:AB reaction takes place on the
mast cell surface releasing mediators like 5-HT,
histamines, leukotrienes, prostaglandins etc
Ex: Bronchospasm
 TYPE 2 (AUTO OR ACCELERATED
ALLERGY)
It occurs within 72 hrs of drug administration.

Drug and component of specific tissue cell

act as AG.

The resulting antibodies (IgG,IgM)

bind to target cells, on reexposure AG:AB
reaction takes place on the surface of these
cells, cytolysis occurs.

Eg: Thrombocytopenia
Haemolysis
Organ damage
 Type 3(Delayed allergy)

• It occurs after 72 hrs but within 1-2 weeks of

drug administration.
• These are mediated by circulating antibodies.
• AG:AB complexes bind and precipitate on
vascular endothelium giving rise to destructive
inflammatory response.
Eg: Stevens Johnson Syndrome
(arthritis, nephritis,
mental symptoms)
 TYPE 4 (CELL MEDIATED ALLERGY)
• These are mediated through
production of sensitized T-lymphocytes
carrying receptors for the AG.

• On contact with antigen these T-cells

produce lymphokines which attract
granulocytes and generate an
Inflammatory response.
Eg: contact dermatitis
rashes
fever
 IDIOSYNCRACY
It is 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
uncharacteristic reaction.

Eg: Barbiturates cause excitement

and mental confusion
Chloramphenicol produces serious
aplastic anaemia.
 MISCELLANEOUS ADRS
Photosensitivity:
It is a cutaneous reaction resulting from drug induced
sensitization of skin to UV radiation.
The reactions are of two types :
phototoxic : Drug or it’s metabolite accumulates in skin,
absorbs light and undergoes a photochemical reaction
followed by a photo biological reaction resulting in local
tissue damage.

photo allergic: Drug or it’s metabolites induces a cell

mediated immune response which on exposure to light
of longer wavelengths produces dermatitis.
 TERATOGENICITY
• An agent that causes toxic effects on foetus
is called as teratogen.
• Teratogenecity is defined as foetal abnormalities
caused by administration of drugs during
pregnancy.
Eg: Thalidomide disaster resulted in
thousands of babies born with phocomelia.
(seal like limbs)
 MUTAGENICITY AND CARCINOGENICITY

• It refers to capacity of drug to cause genetic

defects.

• Usually oxidation of the drug results in

production of reactive intermediates which affect
genes and may cause structural changes in the
chromosomes.
• Covalent interaction with DNA can modifyit to
induce mutations, which may be seen as
heritable defects in the next generation.

 If the modified DNA sequences code for factors

that regulate cell proliferation or growth i.e. are
protooncogenes, or for proteins that inhibit
transcription of protooncogenes, a tumour
(cancer) may be produced.
 MULTIPLE DRUG REACTIONS

• The presence of a second drug may

modify the actions of a simultaneously
administered drug.

• Sometimes drugs are used together

(drug combinations) to obtain a better
clinical response than either drug
could achieve alone.

• In contrast, indiscriminate multiple drug

use can be hazardous as the chances
of ADRS increase with each drug
 FACTORS
• AGE: Infants are at high risk of ADRS because their
capacity to metabolise drugs is not fully developed.

Eg: chloramphenicol - gray baby syndrome

tetracyclines - improper growth of bones
discoloration of teeth
• GENDER: some ADRS are more common in women than
in men. Woman are reputed to be more susceptible to the
toxic effects of digoxin, heparin and captopril.

Eg: chloramphenicol induced aplastic anaemia is

twice as common in women than in men.
 PREGNANCY AND BREAST FEEDING

 Antihypertensive drugs such as angiotensin

converting enzyme inhibitors (ACE) and
angiotensin II receptor blockers pose a risk to
the health and normal development of a foetus.
 During pregnancy requires a doctor’s
supervision.
 Drugs like alcohols, warfarin, lithium, phenytoin
shows some ADRS during pregnancy.
 Some adverse drug reactions

Drug ADR
Paracetamol Liver damage
Anticancer drugs Hair loss & anaemia
Chloramphenicol Gray baby syndrome
Tetracyclines Discolouration of
teeth
Antihistamines Drowsiness
Ephedra extracts Hypertension
 Aspirin and other NSAIDS
These exist their anti inflammatory
effect by inhibition of the enzyme COX.
This enzyme involves in the formation
of prostaglandins. These drugs inhibits
Prostaglandins. Prostaglandins inhibit
the acid secretions. Due to the inhibition
Of prostaglandins acid secretions are
increased. It leads to peptic ulcer
(gastrointestinal bleeding)
 PREVENTION
 Use appropriate dose, route and frequency of drug
administration based on patient’s specific variables.
 Elicit and take into consideration previous history of
drug reactions.
 Elicit history of allergic diseases and exercise caution.
 Adopt correct drug administration technique.
 Avoid all inappropriate use of drugs in the context of
patient’s clinical condition.
REFERENCES

• Tripathi
• Rang & Dale
• Goodmann & Gilman
• Lippincott Williams & Wilkins
• P.N.Bennett
• M.J.Brown