Drug-Receptor Interactions Flashcards
Drug or ligand which binds to the same site as the endogenous ligand and produces the same signal
Agonist
Drug or ligand which binds to a different site than the endogenous agonist without producing a signal itself; it enhances the response of the endogenous agonists
Allosteric agonist
Drug which produces a lower response when at full receptor occupancy than do full agonists (these by themselves evoke a response, but in the presence of a full agonist, they act to competitively inhibit full agonist binding to the receptor)
Partial agonist
Drug that binds to the receptor or components of the effector system used by the endogenous ligand and inhibits the action of the agonist; these initiate no effect themselves
Antagonist
Typical drugs that bind reversibly to the receptor; inhibition can be overcome by increasing the concentration of the agonist, ultimately achieving the same maximal effect
Competitive antagonist
Typical drugs that bind irreversible or allosterically to the receptor; this is a drug that prevents the agonist at any concentration from producing a maximum effect on a given receptor
Non-competitive antagonist
What is the receptor, signal, and response for an agonist, compared to an agonist?
Receptor: same
Signal: same
Response: same
What is the receptor, signal, and response for an allosteric agonist, compared to an agonist?
Receptor: different
Signal: none (by itself)
Response: greater than an agonist (with an agonist)
What is the receptor, signal, and response for a partial agonist, compared to an agonist?
Receptor: same
Signal: same
Response: less than an agonist (b/c not full effect
What is the receptor, signal, and response for an antagonist, compared to an agonist?
Receptor: same (with some exceptions)
Signal: none (just blocks receptor)
Response: less than an agonist
What can look like an antagonist sometimes?
Partial agonist
What is it if the line does not reach 100% on the scale?
Partial agonist
Besides in potentiation, what does the line on the very left represent?
Control (agonist all by itself)
What happens to the max effect during competitive antagonism?
Max effect does NOT decrease; curve just shifts to the right
What kind of bonds are present in competitive antagonism?
Weak ionic bonds (H+ bonds)
In competitive antagonism, as the antagonist goes up, what do we do to combat it?
Give more agonist as well
What happens to the max effect in noncompetitive antagonism?
Max effect decreases b/c it reduced amount of available receptors
What’s the difference between competitive antagonism and noncompetitive antagonism?
Competitive antagonism: curve (max effect) doesn’t decrease, shifts only to the right
Noncompetitive antagonism: curve (max effect) decreases; shifts down and to the right like swinging on a door hinge
What are the 2 types of noncompetitive antagonism that you can have? Which one is more common?
Irreversible or allosteric
Irreversible is more common
What kind of bonds are in noncompetitive antagonism?
Covalent (strong) bonds
In irreversible noncompetitive antagonism, what can’t you do?
You can’t give more agonist to maintain the max effect
What happens to the curve during potentiation?
The curve shifts to the left
What kind of curve is on the left in potentiation?
An allosteric agonist plus an agonist
What can the allosteric agonist in potentiation do?
Enhance activity of agonist, which shifts the curve in the opposite direction of allosteric antagonist
You do a study to see the effect of beta blockers dosage on a patient’s heart rate. The results are below:
10mg dec HR x 10 beats
20mg dec HR x 20 beats
40mg dec HR x 30 beats
80mg dec HR x 30 beats
What can you conclude from this?
- As the dose increases, the response increment diminishes until a dose is reached where no further increase in response can be achieved
- Give pt 40mg at most, because 80mg is not going to do anything extra for the patient
What 2 things do you need to know in order to calculate the effect of the drug?
E(max) and EC(50)
What’s the equation to find the effects of a drug
E = (Emax x C)/(C + EC50)
What’s the equation to find the receptor’s affinity to bind a drug?
B = (Bmax x C)/(C + Kd)
Bmax = total number of receptor sites Kd = concentration of free drug at which 1/2 max binding is observed
When you see Emax and EC50 on a graph, what is being plotted?
Drug concentration per drug effect
When you see Bmax and Kd on a graph, what is being plotted?
Drug concentration per receptor-bound drug
If given a response curve and the Emax, how can you calculate EC50?
- Divide Emax by 2 (ex: Emax can change HR by 100 beats/min, so 100/2 = 50)
- Find where the curve crosses the y-axis at that number (ex: 50)
- Draw line down to x-axis, and this is your EC50 (ex: 5)
Will EC50 and Kd always be the same?
They may be identical, but need not be
Refers to the concentration required to produce 50% of that drug’s maximal response (EC50)
Potency
Reflects the upper limit of the dose-response relation on the response axis (max effect = Emax)
Efficacy
On a response curve, how can you tell if a drug is more potent than another drug?
The further to the left it is, the more potent it is
On a response curve, how can you tell the efficacy of a drug compared to another drug on the same chart?
Look at the height that it goes up to. The higher it goes, the greater the efficacy of the drug
Do we care more about efficacy of a drug or the potency of a drug?
Efficacy b/c we want it to fix the issue, not worrying about the dosage of it if it works
You have a chart that has some drugs with 100% efficacy and some with 50% efficacy. If you want the response to be in the lower part of the chart, which drugs will you pick to achieve this goal?
You can choose any of them because all drugs can achieve this; most likely, you’ll choose based on price
For therapeutic purposes, how should potency of a drug be stated?
In dosage units and in terms of a therapeutic endpoint (ex: 50mg for mild sedation; 1mg/kg/min for an increase in HR of 25 beats/min)
In the in-class case, raloxifene took the place of estrogen, not hindering it’s effects in the process. What type of drug is raloxifene?
Partial agonist
If TD50 (same as LD50) 130, and ED50 is 4, what is the toxicity of the drug?
130/4 = 32.5
This means that you have to take 32.5 pills to get to toxicity when the recommended dose is 1 pill
When is the graph relatively safe for a drug when discussing toxicity?
If ED50 and TD50 (or LD50) are relatively far apart
How many drugs and receptors are involved with pharmacological antagonism?
2 drugs, 1 receptor
How many drugs and receptors are involved with physiologic antagonism?
2 drugs, 2 receptors
How many drugs and receptors are involved with chemical antagonism?
2 drugs, no receptors
Type of antagonism where drugs may bind to and antagonize action of drug (ex: dimercaprol binds to and chelates lead and other toxic metals)
Chemical antagonism
Type of antagonism where the antagonist produces a physiological action that is opposite of agonist and by a separate mechanism (ex: glucocorticoid hormone can increase blood sugar; insulin would oppose this action; these agents act on distinct receptor-effector systems) (like ANS: parasympathetic vs sympathetic)
Physiologic antagonism
