L3: What happens to drugs in the body

Learning Outcomes

By the end of this lecture, you should be able to:

  • Define pharmacology and distinguish between pharmacokinetics (what the body does to a drug) and pharmacodynamics (what a drug does to the body).

  • Understand drug classifications and the three types of drug names.

  • Describe the four pharmacokinetic processes: absorption, distribution, metabolism, and excretion.

  • Explain factors influencing drug absorption, distribution, metabolism, and excretion.

  • Understand bioavailability and first-pass metabolism.

  • Interpret a plasma concentration-time curve.

Pharmacology Overview

  • Pharmacology: Study of how medicines work and affect the body.

    • Derived from Greek: pharmakon (drug) + logia (knowledge).

  • Two branches:

    • Pharmacokinetics: What the body does to the drug.

    • Pharmacodynamics: What the drug does to the body.

What is a Drug?

  • A substance that, when introduced to the body produces a biological effect for an intended purpose.

  • Often treats symptoms (not causes), e.g., antimicrobial drugs.

  • Types:

  • Small molecules

  • Biologics (proteins, antibodies)

Types of Drug Names

Type

Audience

Characteristics

Chemical Name

Chemists

Describes the complex chemical structure (need to know the functional grp before changing the struc

Generic Name

Pharmacologists

Indicates use, action, or structure

Brand Name

Public

Marketing name, varies by manufacturer/country, made to be memorable

Example: Lipid-lowering drugs (-vastatin): atorvastatin, fluvastatin, pravastatin

Pharmacokinetics: What the Body Does to a Drug

  1. Absorption – Will it get in?

  2. Distribution – Where will it go?

  3. Metabolism – Will it remain intact?

  4. Excretion – Will it stay in?

1. Drug Absorption

  • Movement of a drug from administration site to systemic circulation.

  • Routes: oral (most common), IV, nasal spray, subcutaneous.

  • Absorption influenced by:

    • Physicochemical properties:

      • Molecular size: larger = poorer absorption

      • Lipophilicity vs. hydrophilicity: some lipophilicity needed to cross epithelial cell membranes

      • Ionisation: only neutral (not ionised) molecules cross membranes passively as lipids are not good conductors

    • Biological factors:

      • Local pH, determines whether the drug is ionised to what extent

      • GI motility, eat before drinking so that slow down the movement of the gut to slow down absorption of alcohol

      • Enzymatic breakdown in gut wall

      • Transporters (can return drugs to gut lumen)

2. Drug Distribution

  • Reversible passage of drug between tissues, organs and compartments.

    • low plasma conc indicates widely distributed drug

  • Influenced by:

    • Lipophilicity/hydrophilicity:

      • Hydrophilic = stays in bloodstream

      • Lipophilic = accumulates in fat

    • Plasma protein binding: only free drug distributes

    • Blood-brain barrier: tight junctions, transporters

    • Blood flow:

      • Well-perfused: heart, brain, liver, lungs

      • Poorly perfused: resting muscles, fat

3. Drug Metabolism

  • Chemical transformation of a drug into metabolites.

  • Not all drugs undergo metabolism.

    • what goes in also comes out e.g. penicillin

  • Can be mediated by enzymes (act as catalysts).

  • Alters drug activity:

    • Active → inactive (most common)

    • Active → active

    • Active → toxic ft

    • Prodrug (inactive) → active

  • increases hydrophilicity of metabolites: ↓ lipophilic drug accumulation in tissues

Influencing factors:

  • Genetics: alters the expression and/or activity of enzymes

  • Disease (e.g., liver disease)

  • Ageing: ↓ liver function

  • Other medications: competition on which drug is metabolised

4. Drug Bioavailability

  • Fraction of administered does of the parent drug reaching systemic circulation.

  • IV drugs: 100% bioavailability.

  • Oral drugs: affected by absorption and first-pass metabolism (what is left after gut wall and liver).

  • Influenced by same factors as absorption.

5. Drug Excretion

  • Refers solely to the physical processes that lead to the irreversible its metabolites from the body

  • ~25% excreted unchanged.

  • Routes:

    • Urine (most important): filtration, secretion, reabsorption

    • Faeces (via bile)

    • Breast milk

      • newborns may be exposed to drugs through milk intake

    • Expired air (e.g., anaesthetics)

    • Hair, skin/sweat

Plasma Concentration-Time Curve

  • Key parameters:

    1. Minimum toxic concentration

    2. Minimum effective concentration

    3. Duration of action

    4. Therapeutic window

Revision Questions

  1. Define drug absorption and describe one physicochemical property affecting it.

  2. Drug A is found in the brain 30 mins after IV administration. Which process explains this?

    • Correct answer: B. Distribution

  3. How does blood flow influence drug distribution?

  4. Name the two plasma concentrations that define the therapeutic window.