Pharmacodynamics Flashcards
Name 4 targets for drug binding
Receptors
Ion Channels
Carrier Molecules and treansporters
Enzymes
What is an Agonist
Drug that binds to receptors and initiates a cellular response
What is the difference between a partial agonist and a complete agonist
Partial agonists act on the same receptor but do not produce the same maximal response as an agonist
What is an inverse agonist
acts on the same receptor but produces an opposite effect
Stabiles the receptors in the inactive state
Give an example of an inverse agonist
Histamine - H! receptors
Cetirizine/loratadine
Dopamine - Haloperidol
Olanzapine
What are the 2 types of Antagonism
Competitive and non-competitive
Define Competative antagonism
Competitive antagonists - bind to the same receptor as the agonist/ligand but do not elicit a response as the structure does differ.
These are reversible so the agonist will eventually have the opportunity to bind.
Note that there are a limited number of receptor available
Define Non-competative anatagonism
Non-competitive antagonists - bind to a separate receptor site on the same cell. These are irreversible and cannot be displaced (unlike the competitive antagonists). The agonist can still bind to the active receptor site but due to the presence of the non-competitive antagonist, it cannot produce its response (as the overall receptor shape has changed due to the presence of the non-competitive antagonist)
What is a Receptor
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
What is a Ligand gated Ion channel
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.
Neurotransmitter binds to the extracellular domain it causes a structural changes which either opens or closes the ion channel (allowing ions to enter or leave the channel)
What is a G-protein coupled reaction
G-protein receptor found within the phospholipid bilayer, activated by signaling molecule, activates enzyme channel leading to cellular response, then the GTP is hydrolyzed and the enzyme becomes inactive
Receptor Kinases -
Activate cascades of intracellular signals
Most are receptor tyrosine-kinases and are activated by growth factors
Examples: Insulin, growth factors
Action:
They work when a signal molecule causes the 2 receptor polypeptides to aggregate and form a dimer
This activates the tyrosine kinase parts of the dimer
Each phosphorylates the tyrosines on the tail using ATP
Receptor proteins are now recognized by relay proteins inside the cell, which bind to the phosphorylated tyrosines
What are nuclear receptors
Found within the cytoplasm and entirely act within the cell.
Eg Steriods
Intracellular receptors are entirely intracellular. Ligands/drugs must have sufficiently lipid solubility to allow it to pass the cell membrane (lipophilic), to allow a drug-receptor complex to form and elicit a response.
What are enzymes
Macromolecules usually made of proteins
Acts on specific molecules - substrates
Have a specific area of action - active site
What affect can drugs have on enzymes
Competitive inhibitors: bind to active site. The inhibitor and substrate competing for the same active site
Non-competitive inhibitors: binds to a second binding site (allosteric site). Causes change in the enzyme structure thereby reducing activity
