Defining Adverse Drug Reactions
According to the World Health Organization (WHO), an adverse drug reaction (ADR) is a response to a drug that is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease [1.11.2]. It is important to distinguish ADRs from side effects. While the terms are often used interchangeably, side effects are generally predictable, often unavoidable effects that may be undesirable or even beneficial, whereas ADRs are specifically harmful and unintended reactions [1.11.1, 1.11.2]. ADRs represent a significant burden, with some studies indicating they cause up to 30% of hospital admissions in older adults [1.8.3].
What are the 4 Adverse Drug Reactions?
The most widely used classification system for ADRs categorizes them into types based on their mechanism and characteristics. While this system has been expanded to include more types (like Type E for End-of-Use and Type F for Failure), the four core types provide a fundamental framework for understanding these events [1.2.4, 1.3.2].
Type A: Augmented Reactions
Type A reactions are the most common, accounting for up to 90% of all ADRs [1.4.3]. They are a direct, exaggerated extension of the drug's known pharmacological effects [1.4.4].
- Characteristics: These reactions are predictable, dose-dependent, and typically have low mortality [1.2.4, 1.2.5]. The effects usually cease when the drug dose is reduced or stopped [1.2.2].
- Examples: Common examples include bleeding caused by the anticoagulant warfarin, respiratory depression from opioids, drowsiness from older antihistamines, or hypoglycemia from insulin [1.4.1, 1.4.2, 1.4.4].
- Management: Management involves reducing the dose or temporarily withholding the drug [1.2.5].
Type B: Bizarre (or Idiosyncratic) Reactions
Type B reactions are much less common but are often more serious. They are unrelated to the drug's known pharmacological action and are therefore unpredictable [1.2.4]. These reactions are frequently driven by patient-specific factors, such as immunological or genetic predispositions [1.5.2, 1.10.2].
- Characteristics: They are not dose-dependent and have a higher rate of mortality compared to Type A reactions [1.2.5].
- Examples: Examples include anaphylaxis from penicillin, skin rashes from certain antibiotics, or severe liver injury caused by a specific drug in a susceptible individual [1.5.3, 1.4.1]. Genetically-linked reactions, like hemolytic anemia in patients with a G6PD deficiency who take primaquine, also fall into this category [1.5.1].
- Management: The offending drug must be stopped immediately and avoided in the future [1.2.5].
Type C: Chronic (or Continuing) Reactions
Type C reactions are associated with the long-term, cumulative dose of a drug [1.2.4]. They develop over time and are not related to the immediate pharmacological effect.
- Characteristics: These reactions are uncommon and are both dose- and time-related [1.2.4, 1.2.5].
- Examples: A classic example is hypothalamic-pituitary-adrenal (HPA) axis suppression from long-term corticosteroid use [1.2.5, 1.4.1]. Another example is osteonecrosis of the jaw, which can be associated with long-term bisphosphonate therapy [1.6.1, 1.6.5].
- Management: Management often requires reducing the dose or withdrawing the drug, which may need to be a prolonged process [1.2.5].
Type D: Delayed Reactions
Type D reactions are time-related and become apparent some time after the use of the drug, often long after the treatment has stopped [1.2.5, 1.6.5]. This delay can make them difficult to link to the causative medication.
- Characteristics: They are uncommon and their onset is significantly delayed [1.6.3].
- Examples: Examples include tardive dyskinesia, a movement disorder that can appear after long-term use of antipsychotic medications, and carcinogenesis (cancer development), such as secondary cancers that can arise years after certain chemotherapy treatments [1.4.1, 1.7.4].
- Management: These reactions can be intractable or very difficult to treat [1.2.5].
Comparison Table of ADR Types
| Feature | Type A (Augmented) | Type B (Bizarre) | Type C (Chronic) | Type D (Delayed) |
|---|---|---|---|---|
| Relation to Pharmacology | Exaggerated known effect [1.4.4] | Unrelated to known effect [1.2.4] | Related to cumulative dose [1.2.4] | Occurs after treatment [1.2.5] |
| Dose-Dependence | Yes [1.2.5] | No [1.2.5] | Yes (cumulative) [1.2.4] | Usually [1.2.4] |
| Predictability | Predictable [1.2.5] | Unpredictable [1.2.5] | Less predictable | Unpredictable timing |
| Incidence | Common [1.2.5] | Uncommon [1.2.5] | Uncommon [1.2.5] | Uncommon [1.2.5] |
| Mortality | Low [1.2.4] | High [1.2.4] | Variable | Variable |
| Example | Bleeding with warfarin [1.4.4] | Anaphylaxis with penicillin [1.5.3] | HPA axis suppression with steroids [1.2.5] | Tardive dyskinesia [1.4.2] |
Risk Factors for ADRs
Several factors can increase a patient's risk of experiencing an ADR. Key risk factors include:
- Age: Older adults and very young children are more susceptible due to differences in drug metabolism and clearance [1.10.1, 1.10.3].
- Polypharmacy: The use of multiple medications increases the risk of drug interactions and ADRs [1.8.1, 1.10.1]. Taking five or more medications is a significant risk factor [1.8.1].
- Genetics: Genetic variations can affect how the body metabolizes drugs, predisposing some individuals to reactions [1.10.2].
- Coexisting Conditions: Impaired kidney or liver function can hinder drug elimination, increasing risk [1.10.1]. Conditions like HIV infection can also increase susceptibility to certain ADRs [1.10.2].
- Gender: Women may be more susceptible to certain types of ADRs due to differences in pharmacokinetics and body composition [1.10.2].
The Role of Pharmacovigilance and Reporting
Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem. Patient and healthcare provider reporting of suspected ADRs is a cornerstone of this process. In the United States, the FDA's MedWatch program is the primary system for collecting these reports [1.9.2]. Reporting even suspected reactions helps regulatory bodies monitor drug safety, identify new safety signals, and protect public health [1.9.2, 1.9.3].
Learn more about reporting serious drug reactions at FDA MedWatch
Conclusion
Understanding the four main types of adverse drug reactions—Augmented, Bizarre, Chronic, and Delayed—is essential for safe and effective medication use. While Type A reactions are common and manageable, Types B, C, and D can be severe and unpredictable. Recognizing the risk factors and knowing when and how to report a suspected ADR are critical actions for every patient and healthcare provider. Open communication with your doctor or pharmacist about all medications you are taking, including over-the-counter products and supplements, is the best strategy for minimizing risk.
