Mechanisms of Drug Action Flashcards
(16 cards)
Ranges of things that can act as messengers
Ions/Gases; all the way to amino acids, lipids, peptides and protein hormones
Dont memorise these lol just be aware that there’s a huge range (both physically but also in size)
Four main super-families of receptors (and time taken for activation)
Ligand Gated Ion Channels (ms)
G-Protein Coupled Receptors (sec-min)
Catalytic Receptors (min-hour)
Nuclear Receptors (hour-day)
What do agonists do to inactive membrane receptors
Generally causing a conformational change that leads to its activation
Can cause the g-protein to dissociate and cause pharmacological response (where relevant)
Beta Adrenoceptor 1 vs 2
Beta Adrenoceptor 1 on heart
B2 on lungs
(remember 1 heart, 2 lungs)
Amplification
Result of receptor activation
Can occur through molecules such as cAMP which rises in concentration in the cell and affects other processes
Also Ca (associated with contraction or neurotransmitter release)
Drug targets
Enzymes
Transporters
Ion Channels
(Inhibitors)
Receptors
(Agonists and Antagonists)
Affinity
Ability of drug to bind its receptor
We want lower affinity value so less drug needed to bind to receptor; high affinity
Efficacy
Ability of drug, once bound, to activate the receptor by conformational change
Higher efficacy means higher response
Agonist has efficacy, antagonist has 0 efficacy
Affinity of Antagonists
They bind to their receptor targets and block messenger/agonist responses
How do we obtain numbers that estimate affinity
Koff/Kon=KD=[D][R]/[DR]
At equilibrium
Dissociation constant gives measure of affinity
Receptor occupancy
If [D]=KD then 50% of receptors are occupied
KD can be defined as concentration of drug needed to occupy 50% of receptors
Why is KD useful
Allows comparison of drugs of similar function to find drugs that need least concentration
Also allows comparison of better selectivity between similar function drugs
Compare agonists
Sometimes some drugs have higher affinity but lower efficacy than other drugs so they must be used depending on the need
Full and Partial Agonists
Full Agonists - Causes 100% response (more amplification than partial agonists)
Partial Agonists - Cannot cause full response even when all receptors are bound
Why can full agonists like adrenaline cause full responses without binding to all receptors
Receptor reserve - amplification
Are antagonists reversible and competitive
They can be but they can also be non-reversible and non-competitive
