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Online Lecture: Pharmacodynamics.

Chemistry of Receptors and Ligands

Receptors are typically glycoproteins located in cell membranes that specifically recognize and bind to ligands.

These are smaller molecules (including drugs) that are capable of 'ligating' themselves to the receptor protein.

This binding initiates a conformational change in the receptor protein leading to a series of biochemical reactions inside the cell (‘signal transduction’), often involving the generation of ‘secondary messengers’ that is eventually translated into a biological response (e.g. muscle contraction, hormone secretion).

Although the ligands of interest to prescribers are exogenous compounds (i.e. drugs), receptors in human tissues have evolved to bind endogenous ligands such as neurotransmitters, hormones, and growth factors.

Formation of the drug-receptor complex is usually reversible and the proportion of receptors occupied (and thus the response) is directly related to the concentration of the drug.

Reversibility enables biological responses to be modulated and means that similar ligands may compete for access to the receptor.

The term 'receptor' is usually restricted to describing proteins whose only function is to bind a ligand, but it is sometimes used more widely in pharmacology to include other kinds of drug target such as voltage-sensitive ion channels, enzymes and transporter proteins.

Molecules (eg, drugs, hormones, neurotransmitters) that bind to a receptor are called ligands.

The binding can be specific and reversible.

A ligand may activate or inactivate a receptor; activation may increase or decrease a particular cell function.

Each ligand may interact with multiple receptor subtypes.

Few if any drugs are absolutely specific for one receptor or subtype, but most have relative selectivity.

Selectivity is the degree to which a drug acts on a given site relative to other sites; selectivity relates largely to physicochemical binding of the drug to cellular receptors.

 

Click below for a Presentation - Chemistry of Receptors and Ligands.

Synopsis:



Lecture:

Literature:

Forces in Drug-Receptor Binding
Forces in Drug Binding to Receptors.docx (2.22MB)
Forces in Drug-Receptor Binding
Forces in Drug Binding to Receptors.docx (2.22MB)


 




Type of Drug Receptors


 

 Drug - Receptor Interaction / Dose-Response Relationship

 

Drug dose–response relationships are important in assessing the efficacy and potency of drugs.

They are also useful for the interpretation of drug and receptor interactions.

There are two types of drug dose–response relationships, namely, the graded dose–response and the quantal dose–response relationships.

In the graded dose–response relationship, the tissue will respond to the administered drug until it reaches maximal response as the drug concentration is increased.

The occupancy of the receptors by the drugs also plays a critical role in determining the response and is stated to be proportional. A drug’s potency can be derived from a graded dose–response curve.

The EC50 is the concentration which brings about 50% of the maximal tissue response and is used to determine the potency of drugs.

Quantal dose–response curves describe responses in a noncontinuous way and are usually used for the determination of toxic, therapeutic, and lethal doses of drugs during development, specifically, TD50, ED50, and LD50 values.

The concept is to generalize a result to a population, rather than to examine the graded effect of different drug doses on a single individual or experimental specimen.

TD50 is the dose which 50% of the participants showed a toxic response.

ED50 is the effective dose which 50% of the participants received the therapeutic effect and is also used to determine the potency of drugs.

LD50 is the dose which causes death in 50% of the participants.

The ratio of the TD50 and ED50 is used to determine the therapeutic index of a drug, which is a numerical index of the drug’s safety.

 

Click below for a Presentation -  Drug - Receptor Interaction / Dose-Response Relationship.

 

 Synopsis:


Lecture:

 Literature:

 

Efficacy and Receptor Reserve