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Before discussing pharmacodynamics in depth, it is important to define the term and distinguish this branch of pharmacology from the branch called pharmacokinetics.


Pharmacokinetics is the branch of pharmacology that studies the relationship between time and the concentration of a drug at various sites in the body, by measuring the absorption, distribution, metabolism, and excretion of the drug.

Pharmacodynamics studies the effects of a drug on the body by measuring drug binding to receptors and dose-response curves.

Knowledge of how drugs act on receptors will help you understand why and how drugs have particular effects on the body.

*Drugs usually act through binding specific cell receptors within the body.

RECEPTORS

Receptors are molecular complexes within or on the surface of a cell that selectively bind specific substances, also referred to as ligands, and elicit a response on the cell or organism.

Upon administration, a single drug molecule can bind to a wide variety of biological molecules as it circulates throughout the body. In most cases, this binding does not produce any biological effect. However, if the binding of a drug to a biological molecule leads to an effect, the molecule is classified as a drug receptor. The majority of drug receptors are regulatory molecules, which also act as receptors for endogenous ligands such as hormones or neurotransmitters. Though several types of molecules may function as drug targets, most drug receptors are proteins.

There are four major types of receptors in the body:

  • G protein-coupled receptors
  • Enzyme-linked receptors
  • Ion channels
  • Nuclear Hormone receptors

LIGANDS

Endogenous molecules and drugs can serve as receptor ligands. Ligands can be classified as agonists or antagonists, based on the biological effect they have on their corresponding receptor. Ligands can also be categorised based on their binding site on a target receptor, which can be the primary active site or a different region on the receptor called allosteric site.

AGONISTS

Drugs may be agonists, which activate receptors.

Agonists are ligands that, upon binding to a receptor, evoke its activation.

Agonists can be divided into two classes, depending on the ability to activate the receptor.

  • Full agonist
  • Partial agonist

ANTAGONISTS

Drugs may be antagonists, which prevent receptors from being activated.

Antagonists are ligands that, upon binding to a receptor, inhibit its activation. Once bound to the receptor, antagonists block the potential binding of endogenous agonists that would otherwise activate the receptor.

Antagonists can be divided into reversible and irreversible antagonists, depending on the way they interact with receptors.

Antagonists can also be classified as either those that compete with the agonist at the same binding site on the receptor (the active site) or those that bind to a distinct binding site to that of the agonist (the allosteric site) on the same receptor. Agonists of the latter are referred to as allosteric antagonists.

QUANTITATIVE PHARMACODYNAMICS

Scientists and clinicians use mathematical models to describe a fundamental pharmacodynamics relationship when studying a drug – the relationship between the dose of the drug given to the patient and its effects in the body.

Methods used to quantify the relationships between dose, response, and receptor binding include:

  • Dose-response curves: The logarithm of the drug concentration is plotted versus the response
  • The efficacy of the drug: It is determined by the maximum effect of the drug, Emax
  • The potency of a drug: It is determined by the concentration necessary to achieve 50% effect – the EC50
  • The affinity of a drug for a receptor: It is determined by the binding strength of a drug to a receptor – the inverse of KD

Understanding quantification methods will help you better describe the pharmacodynamics properties of drugs.

DOSE-RESPONSE CURVES

The fundamental tool for analysing the relationship between the administered dose of a drug and the physiological response to the drug is known as the dose-response curve. The dose-response curve is a graph that plots the logarithm of the drug concentration on the x-axis and the percentage of the maximum response to the drug on the y-axis.

Several abbreviations are commonly used when describing a dose-response curve:

  • E = the drug effect at a given concentration
  • C = the drug concentration
  • Emax = the maximum effect that can be produced by a drug. A drug with a high Emax is said to have high efficacy
  • EC50 (or half-maximal effective concentration) = the concentration of a drug that produces 50% of the maximum effect. A drug that has a low EC50 – that requires a small concentration to produce 50% of maximum effect – is said to have a high potency

AFFINITY

Drugs that are potent agonists can achieve a full effect before all available receptors have been occupied, whereas other drugs, like partial agonists, may never reach a full effect even if all available receptors are bound. In other words, drug binding and drug effect are not always directly proportional.

The property that quantifies binding strength is known as affinity. It is often measured using the equilibrium dissociation constant (KD).

CLINICAL PHARMACODYNAMICS

Although quantitative methods are key tools for understanding the fundamental relationships in pharmacodynamics, they can be difficult to apply in the clinical setting. Many factors beyond the dose-response curve of a drug will affect the way that a drug functions in the context of patient therapy.

MEASURES OF THERAPEUTIC RESPONSE

All drugs cause more than one (1) single and specific effect. Besides the desired therapeutic effects, drugs may also cause unwanted toxic or adverse effects.

Two (2) clinically relevant measures that compare the therapeutic effects and the toxic effects of a drug are:

  • The therapeutic window; and
  • The therapeutic index.

To understand these measures, it is also necessary to comprehend the concepts of:

  • Median effective dose (ED50)
  • Median toxic dose (TD50)

FACTORS AFFECTING THERAPEUTIC RESPONSE

There is usually a large amount of variation in the response to a drug, both between patients and within an individual patient over the course of treatment.

Some of this variation is due to pharmacokinetic factors such as absorption, distribution, metabolism, and excretion of the drug from the body. However, there are pharmacodynamic factors that can affect the variation response:

  • Incomplete diagnosis
  • Co-administration of other agents
  • Receptor number and function
  • Concentration of endogenous ligands

The following information is a snapshot from ANMF’s Understanding Foundational Pharmacodynamics tutorial on the Continuing Professional Education (CPE) website.

The complete tutorial will give you one hour of CPD.

To access the complete course, please go to anmf.cliniciansmatrix.com

NSWNMA, QNMU and ANMF NT members have access to the course for free.

For further information contact the education team at education@anmf.org.au

anmf.org.au/cpe