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.