ADVERSE

DRUG
REACTIONS

ADVERSE EFFECTS OF DRUGS

Most are
undesirable

All drugs
have
adverse
effects

Inappropriate
drug behavior

From
nuisance to
life
threatening

Subject of
focus of
drug
toxicology

Predictable

Pharmacologic side effect

Dry mouth from antihistaminics

Secondary pharmacologic side

effect

Thrush while taking antibiotics

Drug toxicity

Hepatotoxicity from diclofenac

Drug-drug interactions

Seizure from theophylline while

taking erythromycin (increased
thephylline level)

Drug overdose

Seizure from excessive lidocaine

(Xylocaine)

Unpredictable

Pseudoallergic

Anaphylactoid reaction after

ASPIRIN

Idiosyncratic

Hemolytic anemia in a patient with

G6PD deficiency after ciprofloxacin
therapy

Intolerance

Tinnitus after a single, small dose of

aspirin

What are Adverse Drug Reactions (ADRs)?

any response to a drug

which is noxious and

unintended and which
occurs at doses used in
man for prophylaxis,

diagnosis or therapy

ADRs: 4th Leading Cause of

Death
Study: Drug reactions kill an estimated 100,000 a year
5% of adults are allergic to one or more medications
6 10% of ADRs result from a drug allergy
3% of hospital admissions are due to ADRs
28% of ADRs are preventable
Drugs associated with ADRs: 29% analgesics, 10% sedatives, 9%
antibiotics, and 7% antipsychotics.
PGH: Antibiotics (35%), anti-TB meds (34%), anticonvulsants and
ASA/NSAIDS (10% each)

Key points to remember

ADRs

Common Causes of ADRs

Failing to take the correct dosages at the
correct times
Overdosing
Allergies to chemical components of the
medicine
Combining the medicine with alcohol
Taking other drugs or preparations that interact
with the medicine
Taking a medicine that was prescribed for
someone else.

Causes of ADR

Pharmaceutical causes

decreasing particle size or changing excipients

Pharmacokinetic causes
diazepam
aminoglycosides

Pharmacodynamic causes

increased sensitivity of target organs in the

body to drugs

Factors affecting Adverse Drug Reactions :

Patient-related factors
Age
Sex
Genetic influences
Concurrent diseases (renal,liver, cardiac)
Previous adverse drug reactions
Compliance with dosing regimen
Total number of medications
Misc. (diet, smoking, environmental
exposure)

Factors affecting Adverse Drug Reactions :

Drug-related factors:

Dose
Duration
Inherent toxicity of the agent
Pharmacodynamic properties
Pharmacokinetic properties

Six Classifications of ADR

Type A
Type B
Type C
Type D
Type E
Type F

(Augmented)
(Bizarre)
(Continuous)
(Delayed)
(Ending of Use)
(Failure of Efficacy)

CLASSIFICATION OF ADRs
~According to SEVERITY~

Mild

No therapy , antidote or prolongation of hospitalization is required.

Does not affect patients day-to-day activity

Moderate
Affects patients day-to-day activity to some extent

It requires change in drug therapy, specific treatment or prolongs

hospital stay by at least one day.

Severe

It is life threatening, cause permanent damage or requires intensive

medical treatment.
Adversely affects patients life and is Potentially life threatening

Lethal: Directly or indirectly leads to death

CATEGORIES OF ADVERSE DRUG EFFECT

1.
2.
3.
4.
5.

6.
7.
8.
9.
10.

11.

Side effects
Secondary effects
Intolerance
Idiosyncrasy
Drug allergy
Photosensitivity
Drug dependence
Drug withdrawal reactions
Mutagenicity & Carcinogenicity
Drug induced diseases
Teratogenicity
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ADVERSE DRUG EFFECTS

[1] Side Effects
Unwanted but unavoidable pharmacodynamic effects
therapeutic doses.
Side effect may be based on same action as therapeutic effect.
Eg. Atropine and dry mouth
Codeine and constipation
[2] Secondary effects
Indirect consequences of a primary action of the drug.
a. Super infection due to tetracyclines.
b. Latent tuberculosis activated by corticosteroids.

occuring at

[3] Intolerance:
Opposite of tolerance: sensitivity to low doses
few doses of carbamazepine ataxia [ defective movement/gait]
single dose of triflupromazine muscular dystonia.
Failure to tolerate even a single dose of the drug.
Appearance of characteristic toxic effects of a drug in an individual at therapeutic doses.
Aspirin gastric bleeding
[4] Idiosyncrasy: genetically determined atypical / bizarre effect
Chloramphenicol aplastic anemia.
Barbiturate excitement & mental confusion.
Streptomycin deafness with single dose
[5] Drug allergy: [ or hypersensitivity]
Immunologically mediated
Independent of dose
Occurs in a small proportion;
Prior sensitization required
1-2 weeks required after first dose
Drug acts as an antigen or Hapten
Chemically related drugs may show cross sensitivity
Same drug can cause diff allergic reactions in diff individuals

Immune reaction

Mechanism

Clinical
manifestation

Timing of
reactions

Type I (IgE-mediated)

Drug-IgE complex
binding to mast cells
with release of histamine,
inflammatory mediators

Urticaria, angioedema,
bronchospasm, pruritus,
vomiting, diarrhea,
anaphylaxis

Minutes to hours after

drug exposure

Type II (cytotoxic)

Specific IgG or IgM

antibodies directed at
drug-hapten coated cells

Hemolytic anemia,
neutropenia,
thrombocytopenia

Variable

Type III (immune

complex)

Tissue deposition of
drug-antibody complexes
with complement
activation and
inflammation

Serum sickness, fever,

rash, arthralgias,
lymphadenopathy,
urticaria,
glomerulonephritis,
vasculitis

1 to 3 weeks after drug

exposure

Type IV (delayed, cellmediated)

MHC presentation of
drug molecules to T cells
with cytokine and
inflammatory mediator
release

Allergic contact
dermatitis,

2 to 7 days after
cutaneous drug
exposure

[6]Photosensitivity::
Phototoxic: Drug accumulates in skin absorbs light
photochemical reaction photobiological reaction tissue damage
[Eg erythema, edema, blistering etc] Eg tetracyclines
Photoallergic: drug cell mediated immune response contact
dermatitis on exposure to light. Eg sulfonamides, griseofulvin etc.

[7]Drug Dependence:
Psychological:
Physical dependence
[8] Drug withdrawal reaction
Propranolol hypertension ,worsening of MI
Acute adrenal insufficiency following withdrawal of
corticosteroids
Severe hypertension, restlessness, sympathetic over activity
may occur shortly after discontinuing Clonidine
[9] Drug induced deseases, Iatrogenic diseases :
Salicylates peptic ulcer;
Phenothiazines parkinsonism;

INH hepatitis

[10]Carcinogenicity & mutagenicity:

Anticancer drugs, estrogens

It refers to capacity of a drug to cause genetic defects & cancer

respectively.
Usually oxidation of drug results in the production of reactive
intermediates, which effects genes & may cause structural
changes in the chromosome.
Drugs implicated in these adverse effects are -Anticancer drug ,
radio isotopes, tobacco.

21

[11] Teratogenicity: Drug use in pregnancy affects offspring

Eg Thalidomide phocomelia;
phenytoin cleft palate

It refers to capacity of a drug to cause

abnormalities when administered to the
pregnant mother.
The placenta does not strictly constitute a
barrier and any drug can cross it to a greater
or lesser extent.
The embryo is one of the most dynamic
biological systems and in contrast to adults,
drug effects are often irreversible.

22

Why report ADRs?

To prevent drug-induced human suffering
To avoid financial risks associated with unexpected risks

Who can report ADRs?

Doctors, pharmacists, dentists,
nurses, herbalists, general public
. anyone!

What ADRs can be reported?

Serious
Unexpected
New
Reports are sent to WHO - data added to world-wide data

Medicine

base

Blood product

Herb

Vaccine
Device

How do we report ADRs?

STEP 1 : Fill out the RED ALERT CARDS
STEP 2: Complete the ADR REPORT FORM
The Resident - in - charge of the patient shall complete the necessary report of
ADR circumstances.
STEP 3: Submit the red alert card and the ADR report form to the Central Block
Pharmacy for proper referral.

STEP 4: The Pharmacy will then compile the reports for review of the ADR
Subcommittee and submission to the Bureau of Food and Drugs (BFAD).

IMPORTANT!!!!
The ADR Report Form should include the following:
brand name of the suspect drug

the manufacturer (if generic)

the lot and batch number.

It should be done in duplicate.

ALL REPORTS ARE CONFIDENTIAL

Examples of Reported ADRs

Common reports
rash caused by Oxacillin
red face, fever secondary to Vancomycin
Uncommon reports
hair loss due to anti thyroid agents
neuroleptic malignant syndrome with risperidone

Prevention of ADR:
[1] Avoid inappropriate drugs in the context of clinical condition
[2] Use right dose, route, frequency based on patient variables
[3] Elicit medication history; consider untoward incidents
[4] Elicit history of allergies [in patients with allergic diseases]
[5] Rule out drug interactions
[6] Adopt right technique: Eg slow iv injection of aminophylline
[7] Carry out appropriate monitoring [Eg PT with warfarin; Li
levels]