Pharmacology Chapter on Adverse Reactions

Mechanisms of Action

• Pharmacodynamics: Study of how drugs affect the body; adverse reactions can occur due to unintended interactions with target or non-target receptors.
• Pharmacokinetics: Study of how the body affects drugs; adverse reactions may arise from alterations in absorption, distribution, metabolism, or excretion.
• Idiosyncratic Reactions: Unpredictable reactions not related to dose; often genetically determined.
• Allergic Reactions: Immune-mediated responses that occur when the body recognizes a drug as harmful (e.g., anaphylaxis).
• Toxic Effects: Direct cellular damage due to drug overdose or heightened sensitivity; may involve organ toxicity (e.g., hepatotoxicity, nephrotoxicity).

Types of Adverse Reactions

1. Type A Reactions (Dose-Dependent)

   • Predictable based on drug's pharmacological properties.
   • Examples: Hypotension from antihypertensives, sedation from benzodiazepines.

2. Type B Reactions (Idiosyncratic)

   • Unpredictable and not dose-dependent.
   • Examples: Drug allergies, anaphylaxis, Stevens-Johnson syndrome.

3. Type C Reactions (Chronic)

   • Related to long-term use; cumulative effects.
   • Examples: Tolerance, dependence, and withdrawal symptoms.

4. Type D Reactions (Delayed)

   • Occur after a delay; often associated with carcinogenic or teratogenic effects.
   • Examples: Cancer development from chemotherapeutics, birth defects from certain medications.

5. Type E Reactions (End of Use)

   • Withdrawal reactions after stopping a medication.
   • Examples: Rebound hypertension after stopping antihypertensives, SSRIs withdrawal syndrome.

Risk Factors

• Patient Characteristics

  • Age: Elderly and pediatric populations may be more susceptible.
  • Genetics: Genetic polymorphisms can influence drug metabolism and response.
  • Sex: Hormonal differences can affect drug response.

• Comorbidities

  • Presence of other diseases can increase the risk of adverse reactions due to drug interactions or altered pharmacokinetics.

• Polypharmacy

  • Taking multiple medications increases the likelihood of drug-drug interactions.

• Drug Characteristics

  • Narrow therapeutic index drugs (e.g., warfarin) have a higher risk of adverse reactions.
  • Medications with known side effects or those that are highly protein-bound.

• Environmental Factors

  • Dietary habits (e.g., grapefruit juice interaction with certain medications).
  • Alcohol and tobacco use can potentiate or diminish drug effects.

• Administration Errors

  • Incorrect dosage, administration route, or timing can lead to adverse reactions.

Mechanisms of Action

• Pharmacodynamics: Examines how drugs influence body functions; adverse reactions may result from interactions with intended or unintended receptors.
• Pharmacokinetics: Investigates the processes of drug absorption, distribution, metabolism, and excretion; changes in these processes can lead to adverse effects.
• Idiosyncratic Reactions: Unpredictable responses to drugs unrelated to dosage, often linked to genetic factors.
• Allergic Reactions: Immune system responses where the body identifies a drug as harmful, potentially causing severe reactions like anaphylaxis.
• Toxic Effects: Result from drug overdose or abnormal drug sensitivity, leading to direct cell damage and potential organ toxicity, including hepatotoxicity and nephrotoxicity.

Types of Adverse Reactions

• Type A Reactions (Dose-Dependent): Predictable adverse effects tied to the pharmacological actions of a drug, such as hypotension with antihypertensives and sedation from benzodiazepines.
• Type B Reactions (Idiosyncratic): Unpredictable reactions not linked to dosage, including drug allergies, anaphylaxis, and conditions like Stevens-Johnson syndrome.
• Type C Reactions (Chronic): Associated with prolonged drug use; effects accumulate over time, leading to tolerance, dependence, or withdrawal symptoms.
• Type D Reactions (Delayed): Arise after a delay, often related to carcinogenic or teratogenic outcomes, such as cancer after chemotherapy or birth defects from specific medications.
• Type E Reactions (End of Use): Withdrawal responses after ceasing medication use, exemplified by rebound hypertension following the discontinuation of antihypertensive drugs and withdrawal syndrome from SSRIs.

Risk Factors

• Patient Characteristics:
  • Age: Elderly and pediatric patients exhibit higher vulnerability to adverse reactions.
  • Genetics: Genetic variations may impact drug metabolism and efficacy.
  • Sex: Hormonal differences can alter responses to drugs.
• Comorbidities: Existing diseases may elevate the risk of adverse reactions due to drug interactions or modified pharmacokinetics.
• Polypharmacy: Concurrent use of multiple medications increases the chances of drug-drug interactions and associated risks.
• Drug Characteristics:
  • Narrow therapeutic index medications (e.g., warfarin) are more prone to adverse effects.
  • Drugs with well-known side effects or those that are highly protein-bound present additional risks.
• Environmental Factors:
  • Dietary influences (e.g., grapefruit juice) can interact with certain medications, modifying their effects.
  • Consumption of alcohol and tobacco may enhance or reduce drug efficacy.
• Administration Errors: Mistakes in dosage, route, or timing of administration can result in adverse reactions.

Explore the mechanisms and types of adverse drug reactions in this quiz. Understand pharmacodynamics, pharmacokinetics, and the different types of immune responses associated with drug interactions. Test your knowledge on predictable and unpredictable drug effects.