Pharmacodynamics Flashcards
What are the three steps of cell signalling?
- Reception
- Transduction
- Response
What is a dose?
What is Concentration?
What is Potency?
Dose
- The amount of a drug given to a patient
Concentration
- The amount of something the body produces after a given dose
- Emax is the maximum amount of something produced
Potency
- How much drug is needed to achieve an effect
- EC50 (50% effect) is how big a dose is required to give 50% of its effect
- The lower the dose required to achieve the same EC50, the more potent a drug is
What are the four main drug targets?
Where in relation to a cell are they usually found, and why are they targeted?
Main drug targets
1. Enzymes
2. Carrier Proteins
3. Ion channels
4. Receptors (Most common)
These are usually found on the cell surface because it’s easier to interact with them than intracellular proteins
How many binding sites do receptors have?
What is the chemical that binds to a binding site called?
What is required for these to bind to binding sites?
Receptors have at least 1 binding site
Chemicals that bind to a binding site are called ligands and they require affinity
What happens when a ligand binds to a receptor?
What is efficacy?
An intracellular signalling pathway is triggered when a ligand binds to a receptor
Efficacy is the ability of a ligand to trigger an intracellular signalling pathway
Maximum efficacy = 1
No effect = 0
How can drugs interact with signal transduction?
Drugs can either promote or inhibit signal transduction
What is ligand/receptor selectivity/affinity determined by?
It’s determined by the shapes of the ligand and binding sites
What are the 4 main groups of receptors and what are their associated signalling pathways?
- Ionotropic - Linked to ion channels
- Metabotropic - Linked to G-proteins (G protein-coupled)
- Kinase-linked - Linked to certain enzymes
- Nuclear/intracellular
What are the timeframes of action for the 4 main groups of receptors, and what do they typically do to the cell?
- Ionotropic - Miliseconds, causing hyperpolarisation or depolarisation
- Metabotropic - Seconds, linked to protein phosphorylation
- Kinase-linked - Hours, causing gene transcription and protein synthesis
- Nuclear/intracellular - Hours to days, causing gene transcription and protein synthesis
Do agonistic drugs have receptor affinity and/or efficacy?
Do antagonistic drugs have receptor affinity and/or efficacy?
Agonistic drugs have receptor affinity and efficacy
- Produces a cell signalling response
Antagonistic drugs have receptor affinity but no efficacy
- Binds to the receptor and blocks to it so nothing else can bind
What is receptor basal response?
What is an Inverse agonist?
Basal response is the low level of activity a receptor may exhibit without the binding of a ligand
An inverse agonist is a drug that eliminates this basal low level activity
What types of competitiveness are present in antagonists?
Reversible, irreversible, and non-competitive
What is competitive antagonism (reversible and irreversible)?
Competitive antagonism is when the agonist and antagonist are competing for the same binding site
What differentiates reversible and irreversible competitive antagonism?
Reversible competitive antagonism
- Antagonist binds and releases to the binding site and prevents agonist binding when the antagonist is in the binding site
- Emax is still achieved but just requires a higher concentration
Irreversible competitive antagonism
- Antagonist binds with a covalent bond and doesn’t leave the binding site, disabling that receptor
- Emax is not achieved
What is non-competitive antagonism?
What is a common drug example?
Non-competitive antagonism is when the antagonist doesn’t compete for the same binding site but interferes with the signalling pathway or effects afterwards
A common example is calcium channel blockers for hypertension
Emax is not achieved
