Pharmacodynamics Flashcards
4 receptor types that respond to drugs
Receptors linked to ion channels aka. Ligand Gated Ion Channels or ionotropic receptors
G-protein coupled receptors aka. metabotropic receptors
Enzyme linked receptors
(kinase)
Receptors that affect gene transcription
3 types of G protein coupled receptors and their MOA
- Gs stimulatory
- Gi inhibitory
- Gq stimulatory
Gs – stimulates adenylyl cyclase, causing increased cAMP
Examples include: histamine and serotonin receptors
Gi – inhibits adenylyl cyclase, causing decreased cAMP
Examples include: opioid and cannabinoid receptors
Gq – activates phospholipase C, increasing production of second messengers inositol triphosphate and diacylglycerol
Examples include: prostanoid receptors
Examples of signalling via G-proteins
How do ligand gated ion channels work
Ligand gated ion channels require a ligand to bind to the receptor site which is directly coupled to the gating system, this binding of ligand opens the channel and allow ions to pass through
Influx of Ions into a cell may cause hyperpolarisation or depolarisation
Cl- ions cause hyperpolarisation of cell membranes
Na+ ions cause depolarisation of cell membranes
Hwo to enzyme linked receptors work
Activated by protein based ligands including growth factors, cytokines, hormones e.g. insulin and leptin)
Involved in controlling cell division, growth, differentiation, inflammation, tissue repair, apoptosis, immune responses
3 main types
Receptor tyrosine kinases
Receptor serine/ threonine kinases
Cytokine receptors
How do kinase linked receptors work
They are involved mainly in events controlling cell growth and differentiation, and act indirectly by regulating gene transcription.
Two important pathways are:
MAP kinase pathway – important for cell division, growth and differentiation
JAK/STAT pathway – important for synthesis and release of inflammatory mediators
The interaction of a drug with a target is dependent on two main characteristics of the drug
- Shape - determines ability of the drug to bind
- Charge distribution - determines the type of bonds that holds the drug to the target
2 main principles determine how a ligand and receptor interact
Affinity
How strongly a ligand binds to its receptor
Determined by the strength of chemical bonding
Higher the affinity → higher the potency
Potency
The amount of medication to elicit an effect
High affinity produces an effect at a lower dose
What do agonists do
Activate receptors when bound and produce a subsequent biological response
What do Antagonists do
Associate with receptors but do not cause activation
Antagonists also reduce the chance of an agonist binding to the receptor
They oppose the action of an agonist by theoretically diluting or removing receptors from the system
What does EC50 mean
EC50 is the effective concentration of agonist that elicits 50% maximal response
What is TD50
The toxic dose for 50% of the population
What is therapeutic effect
The response(s) after a treatment of any kind, the results of which are judged to be useful or favorable
What is the therapeutic index
a ratio that expresses the relationship between the dose expected to elicit some adverse effect (e.g TD50) and the dose needed to elicit therapeutic effects
The larger the the therapeutic window the safer the drug
How do competitive antagonists work
Binds reversibly to the active site of a receptor
Compete with the agonist for the binding site
Blocks an agonist from binding to its receptor
This process can be overcome by increasing agonist concentration so the same maximal response can be reached
Agonist alone vs agonist + competitive antagonist graphical differences + similarities
How do non competitive antagonists work
They bind to allosteric site which prevents agonist from binding, increasing concentration of agonist means same maximal response cannot be reached
How to interpret graphs to find efficacy and potency
Compare drug A B and C
Drug A has highest potency and is a full agonist
Drug B has same efficacy has drug A but is less potent and is a full agonist
Drug C has a higher potency than drug B but has lower efficacy than drugs A and B and it is a partial agonist as it has low efficacy
