Lecture 36 - Drug receptor interactions Flashcards
receptors are
macromolecules involved in chemical signalling between and within cells
Cell activity changes once stimulated
Receptor must recognise the molecule and action has to happen
Ligand
molecule that binds to site on receptor
Receptor Occupancy
The fraction of the binding site occupied by the ligand
Dissociation Constant (Kd)
Describes the affinity between a ligand and receptor site
smaller the kD, the more tightly bound the ligand
Agonist
Drug that binds to receptors and initiates a cellular response
It has high affinity and efficacy
Partial Agonists
act on the same receptor but do not produce the same maximal response
Inverse Agonist
acts on the same receptor but produces an opposite effect
Antagonist
Drug that binds to receptors but does not initiate a cellular response
has affinity but no efficacy
Competitive Antagonist
- binds to the same site as the agonist but does not activate it
Non-competitive Antagonist
binds to an allosteric site to prevent activation of the receptor
chemical bonds in order of decreasing bond strength
covalent - ionic - H2 - hydrophobic
Affinity
chemical force that causes drug to bind to the receptor site
efficacy
on binding, extent of functional change imparted to a receptor
potency
dose of a drug needed to produce a biological effect
What is the mass-action relationship in drug-receptor interactions?
only one drug molecule occupies each receptor and binding is reversible
For a given drug the magnitude of the response is proportional to the fraction of total receptor sites occupied by drug molecules
graded and dose dependant
What are the 4 different types of receptors
- ligand gated channels
- G -protein coupled receptors
- enzyme - linked receptors
- intracellular receptors
what are ligand-gated ion channels?
A group of transmembrane ion channel proteins which open to allow ions to pass through the membrane in response to the binding of a ligand such as a neurotransmitter.
E.g. Glutamate, Serotonin, Dopmaine, Acetylcholine
what are G-Protein-coupled receptors?
These receptors are linked to their responses by regulatory Guanosine Triphosphate (GTP)-binding proteins or G proteins
This complex induces conformational change in the G protein
What are second messengers?
Allow signals conduction to be amplifies
eg. ATP, cAMP, PKA
Enzymes that produce second messengers include:
adenyl cylase – involved in activation of protein kinase
Phoplipase C – involved in production of inositol triphosphate (IPS3) and diacyglycerol (DAG)
enzyme-linked Receptors
Activate cascades of intracellular signals
Most are receptor tyrosine-kinases and are activated by growth factors
Intracellular Receptors
The receptor is entirely intracellular
Ligand must be lipid soluble
Primary targets are transcription factors
E.g. steroid hormones
dose -response curves
drug conc vs response - normal curve
drug conc in log scale vs response - sigmoidal curve
what is threshold
dose that
produces a
just-noticeable effect
what is ed 50
dose that produces
50% of maximum response
what is the ceiling of the curve
lowest dose that produces maximal effect
