Definitions
Adverse Drug Reactions
World Health Organization defines ADRs as ‘a response to medicine 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
Side Effect
Is ‘any unintended effect of pharmaceutical product occurring at doses normally used by a patient
that is related to pharmacological properties of the drug’.
This definition was formulated to include side effects that, although are not the main aim of the
therapy, may be beneficial rather than harmful
e.g. a β-blocker agent used to treat hypertension may, by β-blockade, also relieve the patient’s
angina
Adverse Drug Event
Is ‘any untoward medical occurrences that may present during the treatment with a medicine but
does not necessarily have causal relationship with this treatment.
Adverse drug event refers to any adverse outcome that happened during the treatment but not
necessarily caused by the drug itself
REASONS FOR ADVERSE REACTIONS
Most of the incidences of adverse drug reactions may be due to .
1. Dispensing and medication administration errors : In many cases, the physicians overprescribe to
the patient. These prescriptions generally contain potent antibiotics. Similarly, self-medication by the
patients leads to overuse or misuse of the (fruit leading to adverse drug reactions.
2. Failure to set therapeutic end point Potent medicines when abused or misused may cause adverse
effects or even death. Failure of the physician to set the therapeutic end point is the reason for
adverse reactions for drugs like digitalis. corticosteroids. diuretics etc.
3. Bioavailability difference : Difference in the bioavailability from different formulations or brands of
the drug may also cause the adverse drug reactions. Difference to bioavailability from various brands
of digoxin, phenytoin. oxytetracycline have resulted in toxicity in some cases.
4. Patient factors : Physiological and disease status of patient affects adverse drug reaction,. Very
young and old patients are more susceptible to adverse drug reactions compared to the adult this is
due to marked difference in the metabolism and excretion pattern at this age. Similarly, patients
with renal and hepatic damage or dysfunction ar, prone to adverse reaction due to disturbed
metabolism and excretion of drugs Adverse Ante reactions may be due to inherited absence or
deficiency of certain specific enzyme.
Classification of Adverse drug reactions
Adverse drug reactions
A . Predictable B. Unpredictable
1.Excessive 1.Allergic
Pharmaceutical reactions ad
Activity anaphylaxis
2. Secondary
Pharmacological 2. Idiosyncrasy
effects
3. Rebound 3.Genetically
effects on Determined
discontinuation effects
Excessive pharmacological activity:
The most common adverse drug reaction, which may occur, is due to excessive pharmacological
activity of the drug. It mostly occurs due to CNS depressants, hypoglycemics, cardioactive agents and
hypotensive agents. This type of reaction develops in all patients, if excessive dosage is given. But at
normal doses, it is common in patients with more than 70% kidney dysfunction, extreme age range,
i.e. neonates and geriatric patients and patients with lower albumin level due to !cue or kidney
damage. Some examples of this type of reaction are
1) Bradycardia in patients receiving excessive digoxin.
2) Respiratory depression In patients suffering from severe bronchitis if morphine or benzodiazepine
hypnotics are given.
Secondary pharmacological effect: A drug may have ma, pharmacological actions at commonly
administered dosages an adverse drug effect is the pharmacological effect, other than the one for
which the drug was initially administered. e.g patient receiving an antihistaminic for the prevention
of motion sickness may become drowsy Large proportion of adverse drug effects are attributed to
secondary pharmacological effects
Rebound effect after discontinuation: Chronic use of certain drugs produces tolerance at cellular
level, and sudden withdrawal of such drugs produces severe adverse effects This is an unusual
adverse reaction as it occurs due to absence of the drug causing it. This type of reactions is common
with drugs affecting CNS and some hypotensive agents
Typical examples of this type of reactions are as follows
(a) Confusion, delirium, tachycardia, convulsions and extreme agitation followed by lion are
discontinuation of long term CNS-depressants like benzodiazepines, barbiturates and alcohol.
(b) Rebound hypertension on sudden discontinuation of a hypotensive agent clonidine.
(c) Sudden withdrawal of corticosteroids causes acute adrenal crisis (Addison's disease)
characterized by weakness and hypotension in patients. These withdrawal effects can be minimized
by gradual withdrawal of drugs or by substitution with longer acting or less potent agents and
gradual withdrawal.
Unpredictable Adverse Drug Reactions
Allergic drug reactions : Allergy is an adverse response to a foreign substance resulting from a
previous exposure to that substance. It is manifested only after a second or subsequent exposure.
Only a small proportion of the population, exposed to the drug, exhibits allergic reactions.
Characteristics of allergic adverse drug reactions are as follows
1. The reaction does not resemble the expected pharmacological action of the drug.
2. There is delay between the first exposure to the drug and the development of reaction.
3. The reaction recurs on repeated exposure, even to minute quantities of the drug.
Mechanism of allergic drug reaction can be explained on immunological basis. Drug or its metabolite
which is a small molecule, having simple structure generally combines with body proteins. This
stable drug-protein complex acts as an antigen. Simple chemicals which are capable of binding
firmly with a protein to form antigenic product, are termed as 'haptens'.
When an individual comes in contact with such antigenic complex, it stimulates the formation of
antibodies; i.e. sensitization. Such sensitized individual, when re-exposed to the drug or hapten,
antigens react with antibodies. Antigen-antibody complex triggers the release of mediators like
histamine from mast cells. Now, manifestations of allergic reactions occur, which are characteristic
of the mediator and not the drug.
Common allergic drug reaction in human are summarized in the table below :
