Pharmacology Drug Binding Quiz

Introduction to Pharmacology: PharmacoKinetics

• Pharmacology aims to prevent, cure, and control disease.
• Anesthesia involves responses to physiological changes, using sedation, general anesthesia, and amnesia. Analgesia, muscle relaxation, and prevention of complications are also important.
• Safety is crucial in pharmacology.
• PharmacoKinetics studies how the body affects a drug. Dose and plasma concentrations are related here. Factors impacting this include absorption, distribution, metabolism, and elimination.
• PharmacoDynamics studies how a drug affects the body. The relationship between effect site concentration and clinical effects is central here.
• PharmacoBioPhasics focuses on specific areas/effects where drug/receptor engagement creates a clinical effect.

PharmacoKinetics

• Absorption is the transfer of a drug from the administration site into the bloodstream.
• Absorption rate and efficacy depend on the route of administration. Oral intake, injection, inhalation, and topical/transdermal routes are discussed.
• Distribution is the movement of a drug from the plasma into tissues/cells.
• Influencing factors include blood flow to tissues, capillary permeability, and drug structure.
• Molecular size influences how easily drugs cross cell barriers. Smaller molecules typically cross easier.
• Protein binding affects drug distribution.
• Binding to albumin is important.

Factors Affecting Drug Absorption

• Routes of administration: Intramuscular, inhaled, subcutaneous, intravenous, oral, buccal, rectal.
• Blood flow to absorption sites: Heat increases absorption; vasoconstriction decreases it.
• Drug solubility: High lipid solubility (lipophilic) drugs absorb faster.
• Surface area of the absorption site plays a role in absorption rate.

Distribution

• Distribution is the process by which a drug leaves the administration site and enters the plasma and cells.

• Influencing Factors:

  • Blood flow to tissues
  • Capillary permeability
  • Drug structure

• Molecular size influences distribution.

• Active transport requires energy, whereas passive transport follows concentration gradients. This affects drug transfer speed.

Protein Binding

• Drugs bind to plasma proteins, often albumin.
• Bound drug is "trapped" in plasma; free drug enters tissues.
• Protein binding affects a drug's distribution and elimination.

Compartments

• Body water compartments are key for understanding drug distribution.
• The following are included:
  • total body water
  • intracellular fluid
  • extracellular fluid
    • interstitial fluid
    • plasma
• A 70 kg person has approximately 42L total body water; intracellular, extracellular compartments are explained.

Volume of Distribution (Vd)

• Theoretical volume necessary to contain the same concentration of unbound drug in plasma & interstitial fluid
• Larger Vd suggests more drug in tissues compared to plasma.
• Vd is calculated using: Loading dose = Vd x Desired Plasma Concentration.

Metabolism

• Metabolism is the process altering drug structure to make it easier to eliminate, by turning it into a polar/water-soluble form.
• Sites include liver, plasma, kidneys, lungs, and gastrointestinal tract.
• Enzymes are important in this process.
• Metabolism can create active metabolites or inactive products
• Includes oxidation, reduction, and hydrolysis processes.
• The first phase often converts the compound to a more polar form increasing hydrophilicity (water-soluble).
• The second (conjugation) phase adds a polar group to the modified molecule

Elimination

• Elimination is the irreversible removal of drugs from the body.
• Routes include:
  • Kidneys (urine)
  • Liver (bile into feces)
  • Lungs (exhalation)
  • Other (sweat, saliva)

Clearance

• Removal of drug from plasma over time.
• Directly related to organ blood flow, fraction of removed drug and dose.
• Inversely related to the half-life, drug concentration in central compartment.

Hepatic Extraction Ratio

• Comparison of arterial versus venous concentration of a drug reflecting the efficiency of liver extraction.
• "High extraction ratio" suggests a drug extraction and clearance that is flow dependent.
  • Propofol, ketamine, lidocaine, bupivacaine, fentanyl, morphine, metoprolol, nitroglycerin (are all examples of high extraction ratio drugs)
• "Low extraction ratio" suggests a drug extraction and clearance that is capacity-dependent
  • Rocuronium, lorazepam, methadone, thiopental, warfarin, phenytoin (are all examples of low extraction ratio drugs)

Renal Elimination & Excretion

• Renal processes for drug removal
  • Glomerular filtration - process
  • Proximal tubular secretion - process of actively transporting drugs into tubular filtrate
  • Distal tubular reabsorption - process whereby unionized drug potentially passively returns to the bloodstream

Half-Life (t1/2)

• Time for the plasma concentration of a drug to decrease by approximately 50%.
• Factors influencing half-life:
  • Volume of distribution
  • Clearance

Kinetics of Metabolism

• Zero-order kinetics: Constant amount of drug metabolized per unit time.
  • Alcohol, aspirin
• First-order kinetics: Constant fraction metabolized per unit time.
  • Most anesthetics

Steady State

• Steady state reached when the rate of drug administration equals the rate of drug elimination.
• Takes approximately 4-5 half-lives to reach.

Injection and Infusion Kinetics

• Injection and infusion kinetics describe drug movement and/or elimination from body.
  • Important variables include:
    • Distribution
    • Redistribution
    • Metabolism
    • Excretion
• One or multi-compartment models demonstrate how drug distributes in the body.

Multi-Compartment Models

• Two- and three-compartment models demonstrate more complex drug distribution in the body.
• Drug movement between different compartments is dependent upon factors such as:
  • Volume of Distribution
  • Plasma and tissue concentration
  • Rate constants (k)