Intro to Pharm and Tox Topics   

Pharmacokinetic and Phamacodynamics

(sorry this is a bit sketchy)

Pharmacokinetics is the quantitative characterization of the time course of a substance, amount or concentration, in the body compartments or systems of interest (i.e., is it reaching the site of action). Pharmacodynamics is the quantitative characterization of the relationship between drug amount or concentration and the response of the whole animal or system (i.e. is it acting with the desired effect) (??). Both determine the final outcome. After the pharmacokinetics and pharmacodynamics of a drug are defined, they can be used to develop a dosage regime to achieve optimal therapy.

Once absorbed from any site of administration, a drug is distributed by blood to all sites within the body including the eliminating organs. Sites of administration include: artery, peripheral vein, muscle, subcutaneous tissue, lung and gastrointestinal track.

When a drug is given in a fixed dose and at fixed time intervals, it accumulates within the body until a plateau is reached.

The determinants of drug activity include mechanistic/physiological factors and interactions: Mechanistic factors include absorption, distribution, metabolism, excretion, pharmacological effects and clinical response.

Mechanistic factors:

  • Absorption
    • Route and method of administration
    • Dose and dosage regimen
    • Drug delivery system
      • Physicochemical properties of drug
      • Pharmaceutic and manufacturing factors
    • Physiological factors affecting:
      • Gastrointestinal absorption
      • Parenteral absorption
      • Percutaneous absorption
  • Distribution
    • Volume of distribution
    • Plasma protein binding
    • Tissue binding
    • Membrane transport
      • pH partition
      • CSF uptake
    • Cycles
      • Saliva
      • Enterohepatic
  • Metabolism
    • Chemistry
    • Site
    • Rate
    • Capacity of system
      • Enzyme
      • Cofactors
    • Competition for pathway
    • Inhibition/Stimulation of pathway
  • Excretion
    • Urinary
      • Glomerular filtration
      • Tubular secretion
      • Tubular reabsorption
      • Renal clearance
    • Biliary
    • Other (minor)
      • Fecal
      • Lung
      • Skin
  • Pharmacological factors
    • Concentration in biophase (?)
    • Receptor-drug interactions
    • Competition
    • Mechanism of action
    • Effects of body chemistry
    • Toxicology
  • Clinical factors
    • Environmental variables
    • Psychological effects
    • Lack of precision in diagnosis
    • Concurrent diseases
    • Spontaneous relapses and remissions
    • Drug-drug interactions
    • Technical

Interactions:

  • Race
  • Sex
  • Age
  • Body weight and surface area
  • Body position (?)
  • Relative activity
  • Urinary pH (diet, pathology)
  • Urinary flow rate
  • Pharmacogenetics
  • Pregnancy
  • Menopause
  • Nutritional state
  • Pathological conditions
  • Temperature
  • Environmental factors
  • Chronopharmacology (diurnal and circadian rhythms)
  • Blood flow rate
  • Nonspecific and placebo effects

There is PK variability among individuals. This should be addressed by:

Relationship between drug therapeutic effects and drug toxicity. A useful drug will have essentially no toxicity at concentrations yielding maximum therapeutic response. The closer the therapeutic and toxic effect probability curves are, the lesser the usefulness of the drug.

Continue to "Kinetics " or take a quiz: [Q1].

Need more practice? Answer the review questions below.

Questions coming soon