Pharmacodynamics Flashcards
Define pharmacodynamics.
Drug action at the molecular level.
There are 4 classes of endogenous protein that drugs act on to mimic or influence NTs. What are they?
- Enzymes
- Receptors
- Transporters
- Ion channels
What is Kd?
The disassociation constant.
What does Kd tell us?
The concentration of drug required to fill 50% of the receptor sites at equilibrium.
Thus if a drug has a low Kd value, what does it tell us?
The drug has a high affinity for its receptor, as a low concentration is needed to fill 50% of the receptor sites.
What are dose-response curves used to show?
Drug potency.
Define potency.
The ‘strength’ of a drug, essentially how efficiently it acts on its target
What is potency measured by?
ED50.
Define ED50.
The concentration of a drug required to produce 50% of the maximal response.
If a drug is a partial agonist, but has a low Kd and low ED50 value, can it produce a maximal response?
No: even with high affinity and high potency a partial agonist can never produce a maximal response.
With ligand-gated ion channels, the NT is the ligand. Describe the binding between the ligand and receptor.
It is weak, non-covalent association. Thus it is reversible, with rapid association and disassociation.
Why do ligand-gated ion channels produce such fast responses?
Because the receptor IS the effector.
Ligand-gated ion channels are monomeric and extrinsic. True or false?
False: they are multimeric and intrinsic.
There are 3 classes of ligand-gated receptors. What are they?
- Nicotinic
- Glutamate receptors
- GABA receptors
a) which NT binds nicotinic receptors?
b) Describe what happens when this NT binds the receptor.
a) ACh
b) Causes a conformational change that allows Na+ to flood into the cell, producing an excitatory response.
Describe what happens when glutamate binds its ligand-gated receptor.
Makes the cell permeable to Na+. This is the fastest mode of excitation (does not involve shape change).
a) Which GABA receptor is the ligand-gated ion channel?
b) Describe what happens when glutamate binds this receptor.
a) GABA-A
b) Causes a conformational change that causes Cl- to flood in, causing an inhibitory response
Which drugs target GABA-A receptors in the treatment of anxiety?
Benzodiazepines: they cause hypnotic, sedative, relaxant effects
Nicotinic and GABA-A receptors are from the same receptor superfamily. Which superfamily is this?
The Cys-loop ligand-gated channel family
Why are metabotropic receptors so slow?
They involve second messengers that activate ligand-gated ion channels.
What is another name for metabotropic receptors and why?
GPCRs or G-protein coupled receptors: G-proteins are the second messengers.
What happens to GPCRs when a ligand (NT) binds?
G-proteins are activated that act on a wide range of receptors.
Describe what happens in G-protein activation.
GDP is bound to the alpha-subunit. This is phosphorylated to form GTP. Energy from phosphorylation activates the G-proteins. GTP is then hydrolysed back to GDP.
Why can a single ligand binding a GPCR cause a huge response?
G-protein activation is a continuous cycle, so the effect of ligand binding is self-perpetuating.
