Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics Flashcards

Overview of Key Concepts

• Pharmacokinetics: Study of drug disposition over time, encompassing absorption, distribution, metabolism, and elimination (ADME).

• Pharmacodynamics: Examines what drugs do to the body, focusing on their effects and targets such as receptors and enzymes.

• Pharmacogenomics: Investigates how genetic variations affect individual responses to drugs, influencing pharmacokinetics and pharmacodynamics.

Introduction to ADME

• ADME Acronym:

  • Absorption

  • Distribution

  • Metabolism

  • Elimination

• Importance of Learning ADME: Foundation of understanding pharmacokinetics and impacts on drug effectiveness and metabolism.

Key Phases of Pharmacokinetics

1. Absorption

• Definition: The process by which an unchanged drug moves from the administration site to systemic circulation (i.e., blood).

• Factors Affecting Absorption:

  • Drug solubility and formulation.

  • Gastrointestinal conditions (e.g., acidity, presence of food).

  • Gastrointestinal and liver enzyme interactions (first-pass metabolism).

• First-pass Metabolism: Encompasses all metabolic processes before the drug reaches systemic circulation, occurring in the GI tract and liver.

2. Distribution

• Definition: The dispersion or spreading of substances throughout the fluids and tissues of the body.

• Factors Influencing Distribution:

  • Plasma protein binding (e.g., albumin for acidic drugs).

  • Tissue permeability and blood flow occurrences.

  • Drug properties (size, lipid solubility, charge state).

• Volume of Distribution (Vd): An important pharmacokinetic parameter that reflects how extensively a drug disperses into body tissues compared to plasma; can indicate bioavailability.

3. Metabolism

• Definition: The biochemical modification of pharmaceutical substances through metabolic reactions, primarily occurring in the liver (but also in other organs).

• Phases of Metabolism:

  • Phase 1: Modification reactions (e.g., oxidation, reduction) mainly via cytochrome P450 enzymes.

  • Phase 2: Conjugation reactions that increase solubility for elimination (e.g., glucuronidation).

• Factors Affecting Metabolism:

  • Genetic differences in enzyme activity (e.g., ultrarapid vs. poor metabolizers).

  • Drug interactions influencing metabolism rates.

4. Elimination

• Definition: Irreversible removal of drugs from the body, primarily through the kidneys via excretion or through metabolism.

• Clearance: Measurement of the volume of blood or plasma from which the drug is completely removed over time, vital for understanding dosing regimens.

• Half-Life: Time taken for the plasma concentration of a drug to reduce by half; it informs dosing frequency and can be altered by factors like liver function.

Interplay Between Pharmacokinetics and Pharmacodynamics

• The amount of free, unbound drug that achieves systemic circulation influences the pharmacological response observed (pharmacodynamics).

• Genetic variations affect both how a drug is metabolized and its effectiveness. Some populations metabolize certain drugs faster or slower based on enzyme polymorphisms.

Pharmacokinetic and Pharmacodynamic Relationship

• Pharmacodynamics studies drug action and effects while pharmacokinetics examines how the body processes the drug. Their interplay determines overall drug efficacy and safety.

Pharmacogenomics Impact

• Drug response variability is influenced by genetic differences in metabolic enzymes, highlighting the importance of pharmacogenomics in personalized medicine.

Rates and Orders of Reactions

• First Order Kinetics: Rate of drug elimination is proportional to the drug concentration; most drugs behave this way, allowing for predictable dosing and safety.

• Zero Order Kinetics: Rate of elimination is constant regardless of concentration; riskier to manage, can lead to toxicity and accumulation.

Conclusion

• Understanding pharmacokinetic principles is essential for optimizing drug therapy and ensuring safe, effective medication regimens.