ADRs are classified into
1)extended Rawlins and Thompson classification
For
detail of this click here
2)Dots classification
Dots classification of ADRs:
There
are 3 types of Dots classification
A)on
the basis of dose relatedness
B)on
the basis of Time course of ADRs
C)on
the basis of susceptibility
A) Dose relatedness:
In
dose relatedness ADRs are classified into 3 different classes
1)toxic
reactions
2)collateral
reactions
3)hyper
susceptibility reactions
1) Toxic Reactions:
•exaggerated
pharmacological action of drug occur at toxic doses
E.g.
•Toxic
doses of antibiotics cause severe GI infection
•toxic
doses of CCB cause severe headache
Management of Toxic reactions:
Reduce
the dose , duration of drug
2) Collateral reactions:
•most
common
•occur
at Normal doses
E.g.
•non
selective BB (normal dose) cause bronchoconstriction in lungs.
How
Tricyclic antidepressants cause dry mouth?
•Tricyclic
antidepressants (TCAD) block M3 receptor in salivary gland and cause
xerostomia (dry mouth)* classification of ADRs
Management of collateral reactions:
•can’t
manage easily
•Reasure
the patient
•You
can’t avoid it because occur at normal doses tolerate it.
•Do
the symptomatic management
•Change
the therapy if alternative therapy is present.
3) Hyper susceptibility reactions:
•occur
at sub therapeutic doses
•include
all hyper susceptibility reactions
Example of hyper susceptibility reactions:
•
haemolytic anaemia
•idiosyncratic
reactions
Management of hyper susceptibility reactions:
•withdraw
the drug product
•avoid
re exposure
B) Time course of ADRs:
On
the basis of time course ADRs are classified into 6 types
1)Rapid
ADRs
2)First
dose ADRs
3)early
ADRs
4)intermediate
ADRs
5)Late
ADRs
6)Delayed
ADRs
1) Rapid ADRs:
Rapid
ADRs occur due to rapid administration of drug , some drugs should be
administered slowly.
Examples of Rapid ADRs:
•Redmen
syndrome and anaphylactoid caused by rapid infussion of vancomycin injection.
How
redmen syndrome and anaphyactoid is caused ?
Direct
release of histamine by rapid vancomycin administration in whole body i.e.
brain, stomach , vessels.
What
is anaphylactoid reaction ?
Same
as anaphylaxis in clinical features but immune system is not involved but
histamine is involved.* classification of ADRs
Management of Rapid ADRs:
•drug
should be infuse slowly
2) First dose ADRs:
Appear
after first dose of administration do not occur afterward.
Examples of first dose ADRs:
ACEIs
and alpha 1 blockers cause orthostatic hypotension.
Management of first dose ADRs:
Care
should be taken while taking first dose of drug.
3) Early ADRs:
Occur
in early course of therapy, occur
initially for some days but then subside by the concurrent administration.
Examples of early ADRs:
•CCB
and nitroglycerine cause severe headache at the course of time but later the
patient become tolerant.
•Nifedipine
cause persistent ankle oedema which remains throughout the course of time.* classification of ADRs
4) Intermediate ADRs:
Which
occur after some time of the treatment but their chances are reduced with the continuation
of the therapy.
Either
are hypersusceptibility or collateral reactions.
Examples of intermediate ADRs:
Venous
thromboembolism (VTE) by the use of antipsychotic drugs.
5) Late ADRs:
Develop
late as compared to intermediate, occur
after some time and its chances increase with continuous therapy and repeated
exposure of drug.
They
rarely occur or not occur at all.
Examples of Late ADRs:
•PPIs
cause cancer or bone fracture.
•Opium
cause opiate withdrawal syndrome
6) Delayed ADRs:
Develop
late , occur even when the drug is withdrawn,
sometimes they are due to the withdrawal of the drug
Examples of delayed ADRs:
Vaginal
adenocarcinoma caused by DES daughters.
C) susceptibility ADRs:
Risk
of ADRs vary between individuals.
Classified
on the basis of
1)age
2)gender
3)co-morbidity
4)ethnicity
5)pharmacogenetics
Age:
Those
who are extreme of age are at the greater risk of developing ADRs.
New-borns,
neonates, infant are at the greater risk
of developing ADRs.
Because
in these there are no proper development of metabolic organ and excretory
organ. Drugs will remain for higher time in the body.* classification of ADRs
Gender:
Females
are at greater risk of developing ADRs as compared to males. Because in females
water content is low and fat content is high as compared to males.
In
females CYP3A4 is low than males , which metabolize 50% of clinically
significant drug , so in females metabolism is low drug remain for higher time
in the body.* classification of ADRs
Co-morbidites:
Different
chronic diseases such as chronic kidney disease, liver disease, heart disease and patient taking different
drugs (polypharmcy) are at the greater risk of developing ADRs and dose
adjustment is required.
Ethnicity:
Occurs
due to genetic variation.
CYP2C9*1
= wild type in European
CYP2C9*2
= variant type in Asian (poor metabolizer)
Due
to this dose of warfarin is change in Asians and Europeans.
Pharmacogenetics:
The
study of differences in drug response due to variation in genetic composition
of individuals is known as pharmacogenetics .
Some
individuals are sensitive to pencillin
and some are not due to differences in genetic composition.
Pharmacogenomic
: the study of differences in drug response due to difference in genome.* classification of ADRs
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Classification of adverse drug reactions
Types of ADRs
Dots classification of ADRs
Extended Rawlins and Thompson classification of ADRs
Classification on the basis of dose relatedness
Classification Of Adverse Drug Reactions (ADRs)
Classification on the basis of time course of ADRs
Classification on the basis of susceptibility
What is toxic ADRs ?
What is collateral ADRs?
What is hyper susceptibility ADRs?
What is rapid ADRs?
What is first dose ADRs?
What is early ADRs?
What is intermediate ADRs?
What is late ADRs?
What is delayed ADRs?
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