Pharmacology/Receptor Physiology Flashcards
Receptor
protein or glycoprotein which interacts with signaling messenger substance
Ligand
Signaling messenger substance
Ex hormone or drug
‘Initial effect’
Action of drug
‘Succeeding effects’
Drug effects
Law of Mass Action
[L] + [R] <–> [LR]
where formation of L+R is via Ka, separation of L/R into individual components is Kd
[L]=concentration unbound ligand
[R]=concentration unbound R
[LR] = concentration bound R
Ka
rate of constant assoc of L with R
Ka=1/Kd=[LR]/([L]*[R])
Kd
Rate of constant of dissociation of L with R
Affinity
Relationship btw particular R, its L
If amt of ligand administered is just enough to occupy 50% of R then, Ka = 1/[L]
Can a ligand have a strong affinity for the R without producing effect?
Yes
Activity
Ability of ligand to induce an action’
Higher Ka
At equilibrium, number of unbound molecules is low so have high affinity of L for R
Lower Ka
At equilibrium, number of unbound molecules high so have low affinity of L for R
Selectivity of a ligand
determines capacity to produce a particular effect
Highly selective = produce only 1 effect through activity (at only one class/subclass of R
Ex: dopamine vs Dobutamine –> Dobutamine more selective bc only effects at B R, no alpha
Specificity of ligand
capacity to associate with only one specific type of R
o Effects of ligands of highly specific ligand = can be numerous but DT only one type of R-L interaction
Ex: atropine - associates with one specific type of R even though R present in different in tissues, effects diverse
Ex: inhalants - interact with multiple R to produce effects
Limitations to Law of Mass Action
- All L, R equally available to each other
- Binding of drug + R does not alter either drug or R –> not case when drug substrate for R is metabolic enzyme
- Binding of drug to R is reversible…frequently not
- R+drug either bound to each other or not bound ie no ambiguous, partial states
Effect of drug
proportional to concentration of ligand molecules available to bind
Function of dose, method of administration
Lag Time
delay from dosing to onset of pharmacological effects
Can be DT relative difficulty of ligand reaching R (pharmacokinetics) or from post-transduction delay (pharmacodynamics)
Example of a R with lag time
glucocorticoid R = nuclear: when not bound to ligand such as (cortisol, another GC) receptors are located in cytosol
Once activated: complex brought to nucleus –> induces transcription of genes coding from anti-inflammatory proteins, inhibits transcription of genes usually upregulated by inflammatory mediators
Onset of activity = post-transduction (long lag time)
Agonist
ligand that binds to R, usually activates it same way that endogenous molecules would
Full Agonist
Fully activates receptor
Eg morphine
Partial agonist
does not fully activate –> produces less intense maximum effect
ex: buprenorphine
Neutral Antagonist
ligand will bind to receptor, but unable to activate
Assoc usually competitive –> Can be overcome by administrating large enough amount of agonist
Can also be non-competitive
Ex: flumazenil: competitive neutral antagonist at benzo site on GABAA R
Reverse Agonist
ligands activate R but will induce opposite effects to agonist ligands
If R has baseline effect that is not nil, admin of reverse agonist will decrease baseline effect –> ex if agonist effect provides analgesia, then reverse agonist will increase pain sensation
Ex: Ro 19-4603 at benzo binding site on GABAA R
Naloxone
Opioid antagonist but at low doses, enhances analgesia effects
Proposed MOA: increasing effect of endogenous ligands, up regulation of postsynaptic R, inhibiting of counteraction by Gs proteins, uncoupling of filament A, attenuating increase in expression of GFAP