1. Drug- Receptor Interaction

2. Drug-Receptor interaction
I- Ka and Kd
II- Dose response relationship
III- Potency
Understand
Efficacy
Agonist
Antagonist

3. 1 Kd = Ka Drug (D) + Receptor (R) (D) (R) complex Effect versely
Rate of D
binding affinity
Ka = k1/k2 which is association constant K1
to R
Drug (D) + Receptor (R)
Effect
(D) (R) complex
Rate of DR complex to dissociation K2
Kd = k2/k1 or 1/Ka which is equilibrium dissociation constant or affinity constant 1
Kd = Ka
versely
•Kd value reflects affinity of a drug to bind to that receptor.
•Kd is the concentration of that drug that will occupy
50% of a receptor
Kd value and affinity are in
related

4. when a drug has a low Kd. The binding of the ligand to the receptor is …S..t,rong
and the affinity is …..High
Affinity describes the strength of the binding between a ligand & its receptor. The  the affinity, the  the drug conc. required to occupy a receptors.
Affinity is directly related to the potency of the drug (because it determine drug concentration) 1
Kd = Ka K2
The low Kd value, the
the
The higher the Kd value, the weaker the interaction and the lower the affinity Or
higher interaction, K1
higher the affinity & the more potent drug K1
So if a drug has a high affinity for a receptor….., DR complex will be …… & value of Kd will be …S…mall

5. DRUG RESPONSE
The magnitude of the response will be function of fractional occupancy of recep. & the total number of recep. occupied

6. DOSE-RESPONSE RELATIONSHIP
This is the connection between the amount of a drug & the magnitude of the effect produced
Characteristics of curve:
Is the maximal effect of a drug
Steep dose- response curve indicates that small change in dose produces a large change in drug effect
X axis represent Dose
Y axis represent response

7. DOSE-RESPONSE CURVE Hyperbolic curve
Sigmoid curve permits display of a wide range of doses on a single graph
Hyperbolic curve

8. 1- GRADED DOSE-RESPO NSE CURVE
sponse to  drug conc. or dose (the relationshi ation & the magnitude of the response).
simple occupancy theory, but after time it was mo
ug not linearly proportional to the percent of recepto cts could be produced by an agonist occupying o
ay have varying capacities to initiate a response.
esulted in the concepts of drug efficacy and p effects that can be determined from graded d
NSE CURVE
A graph of  re receptor occup
At first there was a
Response of dr
Maximum effe receptors.
Different drugs m
These findings r properties for drug
p between drug dose,
dified due to: rs occupied.
nly a small proportion of
otency (two important ose response curve).

9. POTENCY
Refers to the conc. (EC50) or dose (ED50) of a drug necessary to produce 50% of that drug's maximal response.
Potency can be determined from either graded or quantal dose-response curves.
The potency of a drug depends on:
(1)Receptor affinity for binding the drug (Kd value) (2)The efficiency with which drug-receptor
interaction is coupled to response

10. EFFICACY (E MAX, MAXIMAL EFFICACY)
Refers to the maximal effect (magnitude of response) that can be achieved with a drug, regardless of dose.
Efficacy can be measured with a graded dose-response curve but not with a quantal dose response curve.
Efficacy depends on:
The number of DR complexes formed
The intrinsic activity of the drug
The clinical effectiveness of a drug depends on its maximal efficacy (E max) not on its potency (EC50)

11. INTRINSIC ACTIVITY (INTRINSIC EFFICACY)
Describes the ability of the bound drug to  conformational changes in the receptor (i.e effect of drugs on receptor).
Although affinity is a prerequisite for drug binding to a receptor, a drug may bind with high affinity but have low intrinsic activity.
A drug with zero intrinsic activity is an antagonist.

12. AGONIST Inverse Agonist Full Agonist Partial Agonist S + R S + R Large
Drugs that interact with and activate receptors
Inverse Agonist
Full Agonist
Partial Agonist n
S + R
S + R
conformational changes in R to be active
unable to produce a maximal response eve when it occupies all of the receptors
Large
effect
effect
•Drug has higher affinity for the inactive receptor form (R) than R* & also allow conversion of R* to R.
has affinity but low intrinsic efficacy (<1)
high affinity & high intrinsic efficacy (=1)
e.g: buspirone, buprenorphine, pindolol and salbutamol
Act by reverses the basal
e.g: phenylephrine is an agonist at α1-
adrenoceptors gives effect like NE.
response of the system when it is
due to spontaneous receptor activation (constitutive activity)

13. AGONIST

14. ANTAGONISTS
Antagonists: drugs that  the actions of another drug or endogenous ligand.
Antagonists bind to a receptor with high affinity & zero intrinsic activity
There are 5 types

15. 1-COMPETITIVE ANTAGONISTS:
• Are drugs that bind to, reversible way without ac
1-COMPETITIVE ANTAGONISTS:
or very close to, the agonist receptor site in a tivating the receptor.
Note:
If agonist is given in  conc., this fully activate the receptors & log do shifted to the right
Example: atenolol is β1-adrenocep
will displace competitive antagonist se response curve for an agonist will b
tors antagonist
& e