Pharmacology: Potency and Drug Dosage

Pharmacodynamics

Potency and Efficacy

• Potency: the measure of the drug dosage needed to produce a particular therapeutic effect, determined by the strength of binding of a drug to a receptor or the receptor affinity for the drug.
• Efficacy: the measure of the effectiveness of a drug in producing a maximum response.
• Full agonists have high efficacy, while antagonists have no efficacy.

Dose-Response Measurement

• Used to determine accurate dosing needed when new drugs are formulated.
• Cannot use these measurements to calculate affinity only dosing.
• Agonists bind to receptors causing contractions, which are plotted, and increasing doses lead to increasing responses until two doses have an equal response.

Drug Antagonism

• Competitive (or surmountable) Antagonism: agonists and antagonists compete for the same receptor sites, and the maximal effect remains unchanged.
• Non-Competitive (or irreversible) Antagonism.
• Physiological Antagonism.

Molecular Aspects of Drug Action

• The number of receptors in a cell is not static but dynamic, with a high turnover of receptors as they are continuously removed or replaced.
• Repeated drug treatment may up-regulate or downregulate the receptor numbers.

Tolerance, Desensitisation, and Tachyphylaxis

• Tolerance: the same dose of drug, on repeated administration, produces less effect.
• Desensitisation: less effect is produced the longer the agonist remains in contact with the receptor.
• Tachyphylaxis: tolerance that develops very rapidly.
• Causes of desensitisation/tachyphylaxis/tolerance: change in receptors (phosphorylation), downregulation of receptors (internalisation/reduced expression), depletion of mediator, and increased metabolic breakdown.

Pharmacology and Lifestyle

• Food as drugs – nutraceuticals, and food-drug interactions.
• Exercise: effect of exercise on drugs (pharmacokinetics and pharmacodynamics), activation or induction of antioxidant systems, and effect of drugs on exercise.

The Role of Pharmacodynamics in Pharmacology

• Provides information regarding dose/dosage regimen vs response.
• Factors affecting pharmacodynamics, together with pharmacokinetics, are considered when a dose is individualised for special populations such as the elderly.
• Useful tool for introducing new indications, new dosages, or new treatment populations, contributing to valuable information for drug development.

Introduction to Pharmacodynamics

• Pharmacodynamics is the mechanism by which drugs exert their effect on the body in order for a therapeutic action to occur.
• Pharmacodynamics encompasses drug-receptor interactions and the general principle of drug action.
• Pharmacokinetics is what the body does to the drug.

Types of Drugs

• Drugs with activity at high concentrations: have structural specificity and cause physical change (general anaesthetics).
• Drugs acting at low concentrations: act by chemical rather than physical interaction (Isoprenaline).

Receptors

• The site at which a ligand (agonist) can attach.
• Ligands (drugs) may be neurotransmitters, hormones, or local factors.
• Activation of receptors by a ligand or agonist produces a response (effect).
• Affinity: the attraction of a drug for binding.
• Selectivity: the ability of a drug to bind to a specific receptor.
• Types of receptors: ligand-gated ion channels (fast neurotransmitters) and G-protein coupled receptors (slow neurotransmitters).