Friday, December 28, 2012

Classification of Adverse Drug Reactions



There are several ways of classifying ADRs. The simplest one is that proposed by Rawlins and Thompson which was later modified by Wills and Brown.
I. Rawlins and Thompson classification: In this classification, the ADRs are categorized into two classes viz type A and type B reactions.


1. Type A reactions: These include the reactions that are predictable from the drug’s known pharmacology and are usually dose dependent. Their incidence and morbidity are generally high while mortality is usually, but not invariably low. Examples are bradycardia with b adrenoceptor blockers, hemorrhage with anticoagulants, hypoglycaemia with sulphonylureas, etc. Some type A reactions have a long latency, like teratogenicity, chloroquine retinopathy, delayed effects like vaginal adenocarcinoma in daughters of women who received diethylstilbestrol during pregnancy, etc.

2. Type B reactions: These are aberrant or bizarre effects that cannot be predicted on the basis of the drug’s pharmacology. These reactions are generally unrelated to dosage and though comparatively rare, they often cause serious illness and death. These reactions are often not observed during conventional pharmacological and toxicological screening programmes and consequently account for many drug withdrawals from the market. Some examples are: malignant hyperthermia of anaesthesia, anaphylaxis due to penicillin, and many immunological reactions.
Limitations of Rawlins and Thompson classification: Some of the major limitations of Rawlins and Thompson classification are mentioned below:
1. Everything that is not type A is classified as type B, rendering the later a highly heterogenous group with little in common.
2. Certain ADRs do not fit into either category comfortably; hence it is difficult to decide whether such ADRs are type A or type B.
 
II. Wills and Brown classification: To overcome the limitations of Rawlins and Thompson classification, adverse reactions are classified into nine categories based on their mechanism. In this classification, the term ‘medicine’ has been used in preference to ‘drug’ to ensure that reactions secondary to the method of administration or excipients are clearly incorporated within the definition. Table 1 gives the types and common features of the ADRs as per the Wills and Brown classification.
Table 1. Wills and Brown classification of ADRs
S. No.
Classification of ADR
Features
Examples
1
Type A (Augmented)

i. Relatively common
ii. Pharmacologically predictable
iii. Dose related
iv. Improves if medicine is withdrawn

i. Hypoglycemia with sulfonylureas
ii. Bradycardia with b- blockers, etc.
2
Type B (Bugs)
i. Involves interaction with a microorganism
ii. Pharmacologically predictable
iii. Improves if medicine is withdrawn


i. Dental caries with sugar coated tablets
ii. resistance due to overuse of any one antibiotic, etc.
3
Type C (Chemical)
i. Related to drug concentration
ii. An irritant reaction
i. Extravasation reactions
ii. Phlebitis, etc.
4
Type D (Delivery)
i. Caused by method of administration or nature of formulation
ii. Improves if medicine is withdrawn or method of delivery changed


i. Inflammation or infection around implant particles
ii. Infection at site of injection, etc.
5
Type E (Exit)
i. Pharmacologically predictable
ii.Begins only when the medicine is stopped or dose is reduced
iii. Improves if medicine is reintroduced
i. Withdrawal reactions due to opoids, benzodiazepines, clonidine, b- blockers, etc.
6
Type F (Familial)
 occurs only in the genetically predisposed
i. Hemolytic anemia with primaquin in G6PD deficient individuals, etc.
7
Type G (Genotoxicity)
causes irreversible genetic damage
i. Teratogenic agents like thalidomide causing genetic damage in the fetus, etc.
8
Type H (Hypersensitivity)
i. Requires activation of immune system
ii. Improves if medicine is withdrawn
i. Anaphylaxis with penicillin
ii. allergic skin reactions with antimicrobial agents, etc.
9
Type U (Unclassified)
Mechanism not understood  
i. Taste disturbances with simvastatin
ii. Nausea and vomiting with gaseous anesthetic, etc.

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