Introduction to Pharmacology

Introduction to Pharmacology

• Aims of the session:
  • Outline principles of how drugs work
  • Explain the effects of absorption, distribution, metabolism, and excretion on a drug's action

Definitions

• Pharmacology:
  • The science that explores the composition, effects, and uses of drugs.
• Pharmacokinetics:
  • What the body does to the drug
• Pharmacodynamics:
  • What the drug does to the body

Pharmacokinetics

• Absorption:
  • Drug at the site of administration
• Distribution:
  • Drug in the circulation
  • Distribution in tissues & body fluids
• Metabolism:
  • Drug metabolism
• Excretion:
  • Drug excretion

Absorption and Factors Affecting Absorption

• Oral
• Topical or transdermal
• Subcutaneous
• Intramuscular
• Intravenous
• Inhalation
• Rectal
• Factors:
  • First-pass effect
  • Destruction by enzymes
  • Food
  • Other medications
  • Controlled release drugs
  • Enteric coated drugs

Factors Affecting Absorption Across the Lifespan

• Neonate and Paediatric:
  • Gastric absorption – acid-producing cells immature
  • Gastric emptying - may be decreased
  • Liver not fully mature - ↓ first-pass metabolism with ↑ drug levels in the bloodstream
• Older Adult:
  • ↓ blood flow to tissues in GI tract
  • Changes to gastric pH
  • Variations in available plasma proteins
  • ↓ subcutaneous fat
  • Potential ↓ in cardiac output

Distribution

• Drugs do not distribute evenly throughout the body
• Lipid (fat) soluble drugs concentrate in adipose tissues
• Water soluble drugs concentrate in body water, blood, and interstitial fluid surrounding cells
• Some drugs concentrate in one part of the body
• Drugs penetrate body tissues at different speeds depending on their ability to cross cell membranes
• Blood-brain barrier (BBB) is a selective semipermeable membrane separating the brain

Factors Affecting Distribution Across the Lifespan

• Neonate and Paediatric:
  • ↓ fat content
  • ↓ protein binding capacity
  • Blood-brain barrier still developing
• Older Adult:
  • ↑ body fat
  • ↓ serum albumin

Metabolism

• Metabolism comes from the Greek word that means "to change"
• Liver is the primary site for drug metabolism
• Main purpose to change the drug to become more water-soluble
• Can reduce drug activity or create other active metabolites
• Two phases of metabolism
  • Phase one: Primarily in the liver by cytochrome P450 (CYP4 enzymes)
  • Phase two: A large ionized molecule is added to the drug, increasing its water solubility

Factors Affecting Metabolism Across the Lifespan

• Neonate and Paediatric:
  • Infants and children – Liver not fully developed ↓ enzymes
  • Older Children ↑ metabolism
• Older Adult:
  • ↓ metabolism in liver
  • ↓ first-pass metabolism

Excretion

• Final stage of drug interaction
• Routes:
  • Kidney – most common route, filters blood, majority of byproducts excreted in urine
  • Liver – filters blood, some drugs and their metabolites actively transported to bile
  • Other – Sweat, tears, reproductive fluids (e.g., seminal fluid), and breast milk can contain drugs and metabolites

Factors Affecting Excretion Across the Lifespan

• Neonate and Paediatric:
  • Immature kidneys
• Older Adult:
  • ↓ kidney function
  • ↓ liver function

Therapeutic Window

• A range of drug concentrations in the plasma that is effective and does not cause toxicity
  • Minimum toxic concentration
  • Minimum effective concentration

Factors Affecting Pharmacokinetics

• Patient Factors:
  • Age, sex, medical conditions, pregnancy
• Drug Factors:
  • Solubility in water/lipid; size, electric charge
• Physiological Factors:
  • First-pass effect, barriers (e.g., blood-brain barrier)

Task

• Download or find a copy of the BNF
• Identify pharmacokinetic information for:
  • Metformin
  • Ibuprofen
  • Penicillin (Phenoxymethylpenicillin)