Adverse Drug Reaction (ADR): Definition & Classifications

Definition:

• An ADR is an unintended, harmful reaction that occurs at doses normally used for prophylaxis, diagnosis, or therapy of a disease or for modification of physiological function.

• It's essentially any noxious, unintended, and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, or therapy.
  

Classifications:

Adverse drug reactions (ADRs) can be categorized based on various mechanisms.

Here's a diagram illustrating the classifications of Adverse Drug Reactions (ADRs) based on predictability:

When it comes to predictability, the categorization can be done as:

1. Predictable ADRs:

   1. Excessive Pharmacological Effects: Over-intensification of a drug's desired effect (e.g., too much antihypertensive causing very low blood pressure).

   2. Secondary Pharmacological Effects: Known side effects unrelated to the primary effect (e.g., antihistamines causing dry mouth).

   3. Toxicity Following Sudden Withdrawal: Reactions from suddenly stopping a dependent drug (e.g., antidepressant withdrawal symptoms).

2. Non-Predictable ADRs:

   1. Idiosyncrasy: Unexpected reactions not explained by known drug properties.

   2. Allergic Drug Reactions: Immune-mediated reactions, unpredictable in occurrence.

   3. Genetically Determined Toxicity: Reactions due to genetic predisposition, unpredictable without genetic testing.
      

Let's delve deeper into these classifications of Adverse Drug Reactions (ADRs) and Drug Interactions:

1. Excessive Pharmacological Effects:

• Mechanism: This type of ADR occurs when the therapeutic effect of a drug becomes excessive, often due to overdose but can also result from individual sensitivities.

• Example: An overdose of opioid painkillers can lead to profound respiratory depression because of their known pharmacological effect on the central nervous system.

• Implications & Management: Careful dosing, patient education, and monitoring can help prevent these reactions. In the event of an overdose, prompt medical intervention and possible administration of antidotes or supportive care are crucial.

2. Secondary Pharmacological Effects:

• Mechanism: These reactions arise from the drug's known but secondary pharmacological effects, which are distinct from the primary therapeutic purpose of the drug.

• Example: Antidepressants like SSRIs, designed to elevate mood, can sometimes lead to gastrointestinal disturbances or sexual dysfunction due to their secondary pharmacological effects.

• Implications & Management: Patients should be made aware of these possible side effects, and alternative treatments might be considered if these effects significantly impair the patient's quality of life.
  

3. Idiosyncrasy:

• Mechanism: These are abnormal reactions that aren't an extension of the drug's pharmacological effects and can't be explained by allergic or other mechanisms. They might be due to unique enzymatic/genetic factors.

• Example: Some patients taking the anti-tuberculosis drug isoniazid may develop peripheral neuropathy not because of an allergic reaction but due to their body's inability to metabolize the drug effectively.

• Implications & Management: Recognizing idiosyncratic reactions is essential to prevent severe consequences. Once identified, discontinuing the drug and providing supportive care is often the best course of action.

4. Allergic Drug Reactions:

• Mechanism: These reactions involve the body's immune system treating the drug as a foreign invader, resulting in an allergic response.

• Example: Penicillin can cause allergic reactions ranging from rashes to life-threatening anaphylaxis in susceptible individuals.

• Implications & Management: It's vital to identify and document any drug allergies a patient may have. In cases of allergic reactions, the drug should be discontinued immediately, and appropriate medical intervention provided.
  

5. Genetically Determined Toxicity:

• Mechanism: Certain genetic variations can make an individual more susceptible to a drug's toxic effects.

• Example: Patients with a genetic variation known as HLA-B*5701 have an increased risk of a hypersensitivity reaction to the antiretroviral drug abacavir.

• Implications & Management: Genetic screening can identify at-risk individuals. Alternative treatments should be considered for these patients.

6. Toxicity Following Sudden Withdrawal of Drugs:

• Mechanism: Suddenly stopping certain drugs can lead to rebound symptoms or withdrawal reactions.

• Example: Abrupt discontinuation of benzodiazepines, used for anxiety and sleep disorders, can result in withdrawal symptoms like seizures, tremors, and increased anxiety.

• Implications & Management: To prevent these reactions, it's important to taper off such drugs gradually under medical supervision.