Drug Receptor Interactions

Pharmacodynamics - what the drug does to the body
Pharmacokinetics - what the body does to the drug

Pharmacokinetics follows the ADME scheme;

• Absorption
• Distribution
• Metabolism
• Excretion

Definitions

KD = dissociation constant. Measures ability for an object to dissociate into smaller objects.

Clark's Model

• Magnitude of response in proportional to drug-receptor (DR) complex

=> maximal response occurs when all receptors are occupied

EC50

• Concentration of agonist that produces a response which is 50% of its maximum
• Measure of agonist potency
  
• pD2 = -logEC50

Affinity

• Ability of a drug or ligand to bind to a receptor site

Efficacy

• Ability of a drug or ligand to generate a response once bound to a receptor

Potency

• Dose or concentration at which a drug produces an effect

Molecular targets for drug actions

Receptors

• Nicotinic / muscarinic receptors

Ion channels

• Ca2+ channels
• Na+ channels

Enzymes

• Acetylcholinesterase

Carrier proteins

• Noradrenaline transporters

Antagonism

Competitive

• Occupies receptor site but generates no response
• No depression of maximum
• Parallel shifts rightwards
• Reversible
  

Non-competitive

• Covalently binds to receptor site
• Depression of maximum at high concentrations
• Irreversible
• i.e. Phenoxybenzamine (PBZ)

Schild Plot

• Tests for competitive antagonism
• Linear plot = competitive

pA2

• Negative log10 of the antagonist concentration by which it is necessary to double the antagonist concentration to produce the same response as was obtained in the absence of the antagonist

• Only relevant when antagonist is competitive

• Compares relative potency of two competitive antagonists

• pA2 increases = decrease in the concentration of antagonist required to shift the concentration-response curve ( = more potent the antagonist)