Pharmacodynamics Flashcards
What is a receptor?
A class of cellular macromolecules that are concerned specifically and directly with chemical signalling
What is a ligand?
A substance that is bound to a protein
What is affinity?
The tendency of a ligand to bind to its receptor
What is efficacy?
The tendency for an agonist to activate the receptor
What is an agonist?
A ligand that binds to a receptor and alters the receptor state resulting in a biological response
What is an antagonist?
A drug that reduces the action of another drug, usually an agonist. Many act on the same receptor molecule as the agonist
What is a drug?
A chemical that affects physiological function in a specific way
What equation shows the relationship between ligand concentration and receptor occupancy?
A + R —> AR (K+1)
AR —> A + R (K-1)
What is the relationship between concentration and rate at equilibrium?
(K+1)[A][R] = (K-1)[AR]
What is the formula for Pr (Proportion of free receptors)?
[R]/[Rt] where Rt is the initial concentration of free receptors
What is the formula for Par (Proportion of bound receptors)?
[AR]
——
[Rt]
where Rt is the initial concentration of free receptors
What is the Hill-Langmuir equation?
P(AR) = [A] / ([A] + Ka)
What is the equation for the dissociation equilibrium constant?
Ka = (K-1) / (K+1)
What is Kd or IC50?
The concentration at which 50% of the receptors are occupied
What is a drugs MOA?
Its Mechanism Of Action
What type of drug is amitriptyline?
A tricyclic antidepressant
To which receptors is amitriptyline an antagonist?
Norepinephrine (Noradrenaline) Transporter (NET)
Seretonin Transporter (SERT)
Acetylcholine M1-M5 receptors (ACh)
Histamine H1 receptor
How can amitriptyline cause drowsiness?
Amitriptyline acts as an antagonist to the Histamine H1 receptors in the brain when it passes the blood-brain barrier, leading to sedative effects
How can amitriptyline cause a dry mouth?
Amitriptyline acts as an antagonist to the M1-M5 Acetylcholine receptors, which leads to an anti-muscarinic effect
Why can only a few receptors need to be activated to produce a large response?
Signal amplification occurs
What is the equation for the 2 state model of pharmokinetics?
A + R —> AR (K+1)
then
AR —> A + R (K-1)
or
AR —> AR* (Activated) (K+2)
What is a partial agonist?
An agonist that, in a given tissue, cannot cause a full effect, even with 100% receptor occupancy
Which receptor is buprenorphine a partial agonist against?
The µ-opioid receptor
How does the effectiveness of an antagonist decrease as agonist concentration increases?
It decreases
At low agonist concentrations, the antagonist can form a blockade against the agonist so that it cannot bind to the receptor
At high agonist concentrations, the agonist can outcompete the antagonist and overcome the blockade
What is the formula for concentration ratio?
EC50 with agonist / EC50 without agonist
What is the concentration ratio?
The number of times greater concentration of agonist required to give 50% response with an antagonist than without
What is prazosin an antagonist against?
The α-adrenoceptors, allowing it to treat hypertension
What character is used as an indication of antagonist potency?
pA2
How does affinity change as Ka increases?
Affinity decreases as Ka increases
How does affinity change as pKa increases?
Affinity increases as pKa increases
What shape is formed by a logarithmic plotting of the Hill-languir equation?
A sigmoidal curve
What does the Hill-Langmuir equation describe?
The relationship between ligand concentration and the proportion of receptors
What is potency?
An expression of the activity of a drug, in terms of concentration or amount needed to produce a defined effect such as EC50
