Pharmacotherapy Foundations

Pharmacotherapy Foundations

Objectives

• Define pharmacokinetics (PK) and pharmacodynamics (PD)

  • Pharmacokinetics (PK) = what the body does to the drug
    It describes how drug concentrations change over time and includes absorption, distribution, metabolism, and excretion (ADME).

  • Pharmacodynamics (PD) = what the drug does to the body
    It describes the relationship between drug concentration and effect, including therapeutic effects and toxicity.

  PK determines how much drug gets to the site, while PD determines what happens once it gets there.

• Discuss the concept of "therapeutic range" and its Assumptions & objectives that support the concept

• The therapeutic range (or window) is the concentration range where:

  • Drug concentrations are high enough to be effective

  • But low enough to avoid toxicity

  Assumptions:

• Drug effect is related to drug concentration at the site of action

• Higher concentrations generally produce greater effects

• Toxicity also increases with concentration

Objective of therapy:

• Maintain drug concentrations within the therapeutic range for the required duration

• Therapy fails when concentrations are too low (ineffective) or too high (toxic).

• Discuss factors that may cause variability in individual response during clinical use of drugs

  • Interpatient variability occurs because people differ in PK and PD due to:

    • Age

    • Body weight and obesity

    • Genetics

    • Organ function (renal/hepatic)

    • Disease states

    • Drug–drug interactions

    • Environmental factors (smoking, alcohol)

    • Differences in metabolism and clearance

    This explains why standard doses work for some patients but not others, forming the basis for therapeutic drug monitoring and individualized dosing.

• Define and describe basic concepts of clinical pharmacokinetics and key pharmacokinetic parameters:

  • Absorption and bioavailability

    • Absorption: Rate and extent a drug leaves the site of administration and enters the bloodstream

    • Bioavailability (F): Fraction of unchanged drug that reaches systemic circulation

      • Ranges from 0–1 (0–100%)

      • 100% absorption ≠ 100% bioavailability (first-pass metabolism matters)

  • Distribution

    • Movement of drug from blood to tissues

    • Described by volume of distribution (Vd):

      • Large Vd = drug widely distributed into tissues

      • Small Vd = drug stays mostly in plasma

  • Metabolism

    • Enzymatic conversion of drugs (primarily in the liver)

    • Can inactivate drugs or create active metabolites

    • Influenced by genetics, disease, age, and drug interactions

  • Excretion

    • Removal of drug/metabolites from the body

    • Primary route: kidneys (filtration, secretion, reabsorption)

    • Other routes: bile, feces, sweat, saliva, breast milk, lungs

  • Clearance

    • Measure of the body’s ability to eliminate drug

    • Reflects renal and hepatic function

  • Half-life

    • Time for drug concentration to decrease by 50%

    • Depends on Vd and CL

• Compare and contrast children, obese individuals, and the elderly in terms of potential PK differences vs. “normal” adults

  Children

  • ↓ protein binding

  • Neonates: ↓ metabolism and renal excretion

  • Young children: ↑ metabolism

  • ↑ Vd for hydrophilic drugs

  Elderly

  • ↓ hepatic blood flow and mass

  • ↓ renal function (even if labs appear “normal”)

  • ↑ Vd for lipophilic drugs

  • Requires dose adjustments for renally cleared drugs

  Obese Patients

  • ↑↑ Vd for lipophilic drugs

  • ↑ renal clearance

  • Metabolism often normal or increased

  • Dosing may require adjusted or lean body weight

• Describe approaches to assessing hepatic function and determining appropriate drug dosing

  • No single lab test accurately predicts hepatic drug metabolism

  • Liver disease affects:

    • Enzyme activity

    • Blood flow

    • Bioavailability

    • Protein binding

    • Clearance and half-life

  Common markers:

  • Bilirubin (excretory function)

  • Albumin (synthetic function)

  • INR/PT (clotting/synthetic function)

  • AST/ALT (hepatocyte injury)

  Child-Pugh Score:

  • Class A: normal/mild dysfunction

  • Class B: moderate → ~25% dose reduction

  • Class C: severe → ~50% dose reduction

  Dosing approach:

  • Start low

  • Titrate slowly

  • Monitor response and toxicity closely