21 CFR

ADVERSE DRUG REACTIONS

 

Generally, when a drug is developed, it is expected to act exactly at the target site, that is the disease site, and not on any other site in the body system. However, it does not happen so, the pharmaceutical agent shows its influence in other sites of the body as well. Sometimes these influences are considered good and sometimes irritating. Thus, any medicine that is born to produce a therapeutic effect can also produce unwanted undesired effects. 

An adverse drug reaction is an undesired reaction caused by a medicinal product, it may occur from a single dose or prolonged administration of a drug or as a result of the combination of two or more drugs.

The adverse drug reaction is never desired, connected to a clinical trial, and always adverse. This may result in morbidity and mortality so require medical intervention. 

DEFINITION OF TERMS ASSOCIATED WITH ADVERSE DRUG REACTION

ADVERSE DRUG EVENT

According to WHO, any untoward medical occurrence that may present during treatment with a drug, but which may or may not necessarily have a causal relationship with treatment 

ADVERSE DRUG REACTION

According to WHO, a response that is noxious and unintended and which occurs at normal doses is used in humans for prophylaxis, diagnosis or therapy of disease, or the modification of physiological function.

Therefore, an Adverse drug reaction is an Adverse drug event with a causal link to a drug.

COMMON CAUSES OF ADVERSE DRUG REACTION

Pharmacological, immunological, and genetic factors are involved in the pathogenesis of ADRs.

Factors that predispose to pharmacological ADRs include dose, drug formulation, pharmacokinetic or pharmacodynamic abnormalities, and drug interactions. Immunological, and genetic factors are involved in the pathogenesis of ADRs.

Factors which might increase the possibility of the occurrence of ADRs include; extremes of age, gender, multiple drugs, disease state, past history of ADR or allergy, genetic factors, large doses and many other factors.

Factors affecting the occurrence of ADRs are subdivided into five groups; Patient-related factors, social factors, Drug-related factors, Disease-related factors, and ADR-related factors.

Patient-related factors: -

Age, Gender, Maternity status, Foetal development, Body weight and fat distribution, Creatinine clearance category, Allergy

Social factors:  -

Alcohol drinking, Race and ethnicity factors, Smoking

Drug-related factors:  -

Polypharmacy, Drug and dose frequency

Disease-related factors: -

CLASSIFICATION OF ADVERSE DRUG REACTION

Depending on:

1. Type of reaction

Type A	Augmented	It means already known It’s always dose-dependent  Directly related to the pharmacological property of the drug Often identified in preclinical or clinical trials associated with high morbidity and low mortality
Type B	Bizarre	It means strange Unpredictable  Can occur in any patient Is not dose-related Associated with low morbidity and high mortality
Type C	Chronic	Dose-related  Time-related Occurs with long-term use of drug May be irreversible, unexpected, unpredictable
Type D	Delayed	Usually, dose-related Occurs after a time lag.
Type E	End of treatment	Occurs at end of treatment or when the drug is stopped abruptly.
Type F	Failure of treatment	Unexpected reduction in drug’s efficacy or unexpected failure in therapy Dose-related Caused by drug interactions

2. Onset of event

Acute	<60 minutes
Subacute	1 to 24 hours
Latent	>2 days

 

3. Severity of Adverse drug reaction

Minor	No treatment needed
Moderate	Requires treatment
Severe	Requires intensive treatment
Lethal	Directly or indirectly contribute to death

4. Frequency of adverse drug reaction

Very common	> 10%
Common	> 1%   and < 10%.
Uncommon	> 0.1% and < 1%
Rare	>0.01% and 0.1%
Very rare	<0.01%

5. Expectedness

1. Unexpected adverse drug reaction

In the case of already marketed drugs, an ADR not listed in the labelling or an ADR more specific than indicated in the label

In the case of the investigational drug, an ADR not consistent with information about the drug’s risk that appears in the relevant source of documents (protocol, investigators brochure, and consent documents)

2. Expected adverse drug reaction

An ADR whose nature and severity are consistent with product information and there is already a record of the kind of ADR.

6. Others

1. Side effects

Unwanted but often unavoidable pharmacodynamic effect that occurs in therapeutic doses. These are mild in nature and self-resolving.  They can be predicted from the pharmacological profile of the drug and is expected to occur in a given percentage of drug recipients.

2. Idiosyncrasy

Genetically determined abnormal reactivity to a chemical.

3. Intolerance

Appearance of characteristic toxic effects of a drug in an individual at therapeutic doses. Indicates a low threshold of the individual.

4. Photosensitivity

Cutaneous reaction resulting from drug-induced sensitization of the skin to UV radiation. 

5. Drug dependence

Drugs capable of altering mood and feelings are liable to repetitive use to derive euphoria, withdrawal from reality, social adjustment, etc.

6. Teratogenicity

The capacity of a drug to cause fetal abnormalities when administered to a pregnant mother.

7. Mutagenicity

The capacity of a drug to cause genetic defects and cancer respectively.

8. Iatrogenic

Functional disturbances caused by drugs which persist even after the offending drug has been withdrawn and largely eliminated.

9. Carcinogenicity

Chemical carcinogenesis generally takes several (10-40) years to develop.

Serious attention to these factors will result in preventing or reducing the occurrence of unwanted drug actions which could have been avoided if healthcare providers spent enough time to pinpoint these problems.  Finally; for each benefit to come out of medication there is always a possibility for some risks; benefits should always out weight risks for the purpose of providing the best treatment with the least number of medications at the most economic price.

References

Nebeker JR, Barach P, Samore MH (May 2004). "Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting". Annals of Internal Medicine

Ritter, J M (2008). A Textbook of Clinical Pharmacology and Therapeutics. Great Britain. p. 62.

 

Student Name: Fauziyya Shahul Hameed

Student ID: CSRPL_INT_ONL_WKD_202/1222

Qualification: BDS

e-Mail ID: fauziyyas@gmail.com