Pharmacodynamics

What is pharmacology?

The study of the effect of drugs on the systems of living organisms. Greek word meaning medicine or poison

What is a drug?

A chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect

What is a drug target?

Drug molecules have to interact with target to have an effect

• mimic or block endogenous signals

• Therapeutic dose

Targets - any binding site that interacts with a drug

• receptors

• Ion channels

• Carrier molecules (transporters)

• Enzymes

Dose response curves

Examine the relationship between drug concentration and pharmacological response

• how much drug to produce desired effect

Important features

• threshold (start to effect)

• EC50 (half maximum)

• Maximum effect (full response)

Efficiency and potency

Drug-receptor binding - what is efficiency?

Maximum effect that can be produced once binding has occurred

EC50 - concentration that produces 50% of effect between minimum and maximum

Affinity and efficacy influence potency

Drug-receptor binding - what is potency?

Amount of drug needed to give clinical effect

Small amount = high potency

Large amount = low potency

Drug-receptor binding - what is affinity?

The amount of binding to the receptor

High affinity = more binding to more receptors at lower concentrations

Low affinity = less binding; dissociate more easily

What is an agonist?

Mimic the effect of ligand

Can have high affinity, high efficacy

Type 2 diabetes drug (glucagon-like peptide [ GLP-1] drugs)

What is an antagonist?

Block effect of ligand

Can have high affinity, no efficacy

Naloxone

What are the types of agonists?

1. Full agonist

   • can achieve maximal response

   • High efficacy

2. Partial

   • produce submaximal response even with high concentration

   • low efficacy

What is allosteric modulation?

When an allosteric modulator binds to a different site on the receptor to affect activity

Positive - makes more effective

Negative - makes less effective

Also seen in enzymes

Types of antagonists?

1. Irreversible competitive

   • antagonists binds very tightly

   • Can’t be disrupted by agonist

2. Non-competitive

   • bind to a different site

   • Not competing with agonist

What is inhibition (drug-enzyme binding)?

Blocking activity of enzyme

What is competitive drug-enzyme binding?

Same site

Reversible or irreversible

What is non-competitive drug-enzyme binding?

Different site

Conformational change

Reversible or irreversible

How do carrier proteins work?

Act in a similar manner to enzymes

Activity is inhibited

GLUT-4

Na+/K+ pump

What is specificity?

Acts directly on target

What is selectivity?

Acts on one target

Beta blockers

Beta-adrenergic receptors

• increase heart rate

2 subunits - beta1 and beta2

Some drugs just interact with beta1 (selective) e.g. dobutamine

Other drugs interact with both (non-selective) e.g. propranolol

Beta2 receptors

Beta2 receptors also found in lungs, blood vessels, GI tract, bladder, uterus, liver

Will see effects on these organs too

Side effects

• breathing problems, constipation, nausea, dizziness

Local anaesthetics

Lidocaine, articaine (must be unionised)

Disrupt the action potential

Block the movement of Na+

Antagonist

Ipratropium

Antagonist

Penicillin

Inhibitor

Dabigatran

Competitive inhibitor

Ketamine

Non-competitive antagonist