Lecture 5 Flashcards
1
Q
Agonist drugs mimic the action of the original endogenous ligand for the receptor , give me example to explain this statement :
A
isoproterenol mimics norepinephrine on β1 receptors of the heart .
2
Q
As the concentration of a drug increases, its pharmacologic effect also gradually decreases until all the receptors are occupied .( T/F) ?
A
F—> (As the concentration of a drug increases, its pharmacologic effect also gradually increases until all the receptors are occupied)
3
Q
Plotting the magnitude of response against increasing doses of a drug produces a graded dose–response curve that can be described as ?
A
rectangular hyperbola
4
Q
The function of rectangular hyperbola is :
A
Applied to diverse biological events, such as enzymatic activity, and responses to pharmacologic agents .
5
Q
Mention the two important properties of drugs that can be determined by graded dose–response curves :
A
potency and efficacy
6
Q
A measure of the amount of drug necessary to produce an effect of a given magnitude is called?
A
Potency
7
Q
The concentration of drug producing 50% of the maximum effect is called ?
A
(EC50)
8
Q
Mention the use of (EC50) :
A
Is usually used to determine potency.
9
Q
The EC50 for Drugs A and B indicate that Drug A is more potent than Drug B, because a ( lesser / more ) amount of Drug A is needed when compared to Drug B to obtain 50-percent effect .
A
Lesser
10
Q
Therapeutic preparations of drugs reflect ?
A
The potency of it
11
Q
candesartan and irbesartan are angiotensin receptor blockers that are used to ?
A
Treat hypertension.
12
Q
The therapeutic dose range for candesartan is 4 to 32 mg, as compared to 75 to 300 mg for irbesartan. Relying on this information, we can say that :
A
candesartan is more potent than is irbesartan (it has a lower EC50 value, similar to Drug A).
13
Q
Why we need to use semilogarithmic plots ?
A
Because, the range of drug concentrations (from 1% to 99% of the maximal response) usually spans several orders of magnitude , for this reason semilogarithmic plots are used so that the complete range of doses can be graphed.
14
Q
The magnitude of response a drug causes when it interacts with a receptor is called :
A
Efficacy
15
Q
Efficacy is dependent on two factors, mention them :
A
- the number of drug–receptor complexes formed .
- the intrinsic activity of the drug (its ability to activate the receptor and cause a cellular response).
16
Q
The ability to activate the receptor and cause a cellular response called :
A
intrinsic activity
17
Q
When all receptors are occupied by the drug, and no increase in response is observed if a higher concentration of drug is obtained this case called?
A
Maximal efficacy of a drug (Emax)
18
Q
The maximal response differs between full and partial agonists, even when 100% of the receptors are occupied by the drug. (T/F) ?
A
True
19
Q
Antagonist occupies …… % of the receptor sites, no receptor activation results and Emax = ??
A
1- 100 %
2- zero
20
Q
Efficacy is a (more/ less) clinically useful characteristic than is drug potency, since a drug with greater efficacy is (more/less) therapeutically beneficial than is one that is more potent.
A
- more
- more
21
Q
The quantitative relationship that applies the law of mass action to the kinetics of the binding of drug and receptor molecules is ?
A
The quantitative relationship between drug concentration and receptor occupancy
22
Q
We can mathematically express the relationship between the percentage (or fraction) of bound receptors and the drug concentration , Mention this equation
A
[DR]/[Rt]= [D] / (Kd+[D])
23
Q
The symbols in previous equation refer to :
A
- [D] = the concentration of free drug,
- [DR] = the concentration of bound drug,
- [Rt] = the total concentration of receptors and is equal to the sum of the concentrations of unbound (free) receptors and bound receptors,
- Kd = the equilibrium dissociation constant for the drug from the receptor
24
Q
The value of Kd can be used to
A
determine the affinity of a drug for its receptor.
25
Affinity describes the ……… of the interaction (binding) between a …….. and its…….. .
1- strength
2- ligand
3- receptor
26
The higher the Kd value, the (weaker/ stronger ) the interaction and the lower the affinity, and vice versa.
Weaker
27
As the concentration of free drug increases, the ratio of the concentrations of bound receptors to total receptors approaches unity . (T/F) ?
True
28
The binding of the drug to its receptor initiates events that ultimately lead to ?
A measurable biologic response .
29
The mathematical model that describes drug concentration and receptor binding can be applied to dose (drug concentration) and response (or effect), providing assumptions , mention this assumptions :
1) The magnitude of the response is proportional to the amount of receptors bound or occupied,
2) The Emax occurs when all receptors are bound,
3) Binding of the drug to the receptor exhibits no cooperativity.
30
Relying on the previous assumptions, we were able to arrive at a new equation, mention it:
[E] /[Emax] = [D] / Kd+ [D]
- [E] = the effect of the drug at concentration [D]
- [Emax] = the maximal effect of the drug.
31
Thus, it follows that if a specific population of receptors is vital for mediating a physiological effect, the affinity of an agonist for binding to those receptors should be related to the …….. .
Potency of that drug for causing that physiological effect .
32
many drugs and most neurotransmitters can’t bind to more than one type of receptor . (T/F) ?
F—> (many drugs and most neurotransmitters can bind to more than one type of receptor) .
33
many drugs and most neurotransmitters can bind to more than one type of receptor which ……… :
causing both desired therapeutic effects and undesired side effects.
34
In order to establish a relationship between drug occupation of a particular receptor subtype and the corresponding biological response , we use the ?
Correlation curves of receptor affinity and drug potency .
35
Correlation of drug affinity for receptor binding and potency for causing a physiological effect. A positive correlation should exist between the affinity (Kd value) of a drug for binding to a specific receptor subtype and the potency (EC50 value) of that drug to cause physiological responses mediated by that receptor population. For example, many drugs have affinity for both α1 and β2 adrenergic receptors. The circled letters in the figure represent agonists with varying affinities for α1 and β2 receptors. However, from the data provided, it becomes clear that α1 receptors only mediate changes in blood pressure, while β2 receptors only mediate changes in bronchodilation . Show the answer 🌚
If you can't understand what's written above, just call me 😊
36
……………. determines its ability to fully or partially activate the receptors.
The intrinsic activity of a drug .
37
Drugs may be categorized according to their intrinsic activity and resulting Emax values to foure categories, mention them bro :😊
1. Fullagonist
2. Partial agonist
3. Inverse agonist
4. Antagonist
38
If a drug binds to a receptor and produces a maximal biologic response that mimics the response to the endogenous ligand, it is a ?
full agonist
39
Full agonists bind to a receptor, stabilizing the receptor in its active state and are said to have an intrinsic activity of one.
Just note 🌚
40
All full agonists for a receptor population should produce different Emax . (T/F) ?
F—> ( the same Emax)
41
All full agonists for a receptor population should produce the same Emax . Explain this statement through give example :
phenylephrine is a full agonist at α1-adrenoceptors, because it produces the same Emax as does the endogenous ligand, norepinephrine.
42
Upon binding to α1-adrenoceptors on vascular smooth muscle, phenylephrine stabilizes the receptor in its active state. This leads to ?
Mobilization of intracellular Ca2+, causing interaction of actin and myosin filaments and shortening of the muscle cells.
43
agonist may have many measurable effects, including:
1. Actions on intracellular molecules,
2. Cells,
3. Tissues,
4. Intactorganisms.
💕All of these actions are attributable to interaction of the drug with the receptor💕
44
• For full agonists, the dose–response curves for receptor binding and each of the biological responses should be comparable. (T/F) ?
True
45
Which category have intrinsic activities greater than zero but less than one ?
Partial agonists
46
Even if all the receptors are occupied, partial agonists can produce the same Emax as a full agonist. (T/F) ?
F—>( Even if all the receptors are occupied, partial agonists cannot produce the same Emax as a full agonist.)
47
a partial agonist may have an affinity that is greater than, less than, or equivalent to that of a full agonist. (T/F)
True
48
When a receptor is exposed to both a partial agonist and a full agonist, the partial agonist may act as an …………. of the full agonist.
antagonist
49
Consider what would happen to the Emax of a receptor saturated with an agonist in the presence of increasing concentrations of a partial agonist :
As the number of receptors occupied by the partial agonist increases, the Emax would decrease until it reached the Emax of the partial agonist.
50
This potential of partial agonists to act as both an agonist and antagonist may be therapeutically utilized . (T/F) ?
True
51
This potential of partial agonists to act as both an agonist and antagonist may be therapeutically utilized . Give me example to describe this sentence :
Aripiprazole
52
An atypical antipsychot , which is a partial agonist at selected dopamine receptors . This statement describe the :
Aripiprazole
53
Dopaminergic pathways that are over active tend to be inhibited by ?
Aripiprazole
54
This might explain the ability of aripiprazole to improve symptoms of ………….. with a small risk of causing extrapyramidal adverse effects
Schizophrenia
55
pathways that are underactive are inhibited by aripiprazole . (T/F) . 🌚
F—> ( whereas pathways that are underactive are stimulated) .
56
Unbound receptors are inactive and require interaction with an agonist to assume an active conformation. This statement describe any category?
Inverse agonists
57
Some receptors show a spontaneous conversion from R to R* in the absence of an agonist. (T/F) ?
True
58
How inverse agonists work ?
It work unlike full agonists, stabilize the inactive R form and cause R* to convert to R .
59
inverse agonists increase the number of activated receptors to below that observed in the absence of drug . (T/F) ?
F—>(decreases)
60
The features of inverse agonists are?
1. have an intrinsic activity less than zero
2. reverse the activity of receptors
3. exert the opposite pharmacological effect of agonists.
61
The category that bind to a receptor with high affinity but possess zero intrinsic activity called .
Antagonists
62
Antagonist has effect in the absence of an agonist but can decrease the effect of an agonist when present. (T/F) ?
F—>(antagonist has ((no)) effect in the absence of an agonist but can decrease the effect of an agonist when present.) 🌚
63
Antagonism may occur in the receptor from two ways, mention them :
1- by blocking the drug’s ability to bind to the receptor
2- by blocking its ability to activate the receptor.
64
Mention the types of antagonist :
A. Competitive antagonists
B. Irreversible antagonists
C. Allosteric antagonists
D. Functional antagonism
65
If both the antagonist and the agonist bind to the same site on the receptor in a reversible manner, they are said to be ?
Competitive
66
The competitive antagonist prevents an agonist from binding to its receptor and maintains the receptor in its inactive state . (T/F) ?
T
67
Give me example about Competitive antagonists .
The antihypertensive drug terazosin competes with the endogenous ligand norepinephrine at α1-adrenoceptors, thus decreasing vascular smooth muscle tone and reducing blood pressure.
68
This inhibition can be overcome by ……
Increasing the concentration of agonist relative to antagonist.
69
competitive antagonists characteristically shift the agonist dose– response curve to the ………… ((increased / decreased) EC50) without affecting Emax
1. Right
70
Bind covalently to the active site of the receptor, thereby reducing the number of receptors available to the agonist . This statement describe ?
Irreversible antagonists
71
An irreversible antagonist causes a upward shift of the Emax, with no shift of EC50
F —>(An irreversible antagonist causes a downward shift of the Emax, with no shift of EC50 )
72
The effect of irreversible antagonists can be overcome by adding more agonist like competitive. (T/F) ?
F —>(the effect of irreversible antagonists cannot be overcome by adding more agonist)
73
Irreversible antagonists and allosteric antagonists are both considered ?
Noncompetitive antagonists
74
A fundamental difference between competitive and noncompetitive antagonists is that competitive agonists increase agonist potency (reduce EC50) and noncompetitive antagonists increase agonist efficacy (decrease Emax) . (T/F) ?
F —> A fundamental difference between competitive and noncompetitive antagonists is that competitive agonists reduce agonist potency (increase EC50) and noncompetitive antagonists reduce agonist efficacy (decrease Emax)
75
…………. also causes a down ward shift of the Emax, with no change in the EC50 value of an agonist.
Allosteric antagonists
76
Allosteric antagonists type of antagonist binds to a site (“allosteric site”) other than the agonist-binding site and prevents the receptor from being activated by the agonist . (T/F) ?
T
77
Give me example about Allosteric antagonists .
An example of an allosteric agonist is picrotoxin, which binds to the inside of the GABA-controlled chloride channel .
78
What happens when picrotoxin bound inside the channel ?
no chloride can pass through the channel, even when the receptor is fully activated by GABA.
79
May act at a completely separate receptor, initiating effects that are functionally opposite those of the agonist ?
Functional antagonism
80
A classic example is the functional antagonism by ?
epinephrine to histamine-induced bronchoconstriction
81
A classic example is the functional antagonism by epinephrine to histamine-induced bronchoconstriction . Explain this example
• Histamine binds to H1 histamine receptors on bronchial smooth muscle, causing bronchoconstriction of the bronchial tree.
• Epinephrine is an agonist at β2-adrenoceptors on bronchial smooth muscle, which causes the muscles to relax
82
This functional antagonism is also known as ?
“physiologic antagonism.”
83
Important dose–response relationship between the dose of the drug and the proportion of a (population) that responds to it named as ?
QUANTAL DOSE–RESPONSE RELATIONSHIPS
84
Why these responses are known as quantal responses ?
Because, for any individual, the effect either occurs or it does not (all or none ).
85
Graded responses can be transformed to quantal responses by ?
Designating a predetermined level of the graded response as the point at which a response occurs or not .
86
Give me example about quantal dose–response relationship .
For example, a quantal dose–response relationship can be determined in a population for the antihypertensive drug atenolol.
87
(In the previous slide) a positive response is defined as ?
Fall of at least 5 mm Hg in diastolic blood pressure.
88
The drug dose that causes a therapeutic response in half of the population called ?
ED50
89
The ratio of the dose that produces toxicity in half the population (TD50) to the dose that produces a clinically desired or effective response (ED50) in half the population is CALLED ?
Therapeutic index
90
Give me the equation that describe therapeutic index .
TI=TD50/ED50
91
The …. is a measure of a drug’s safety .
TI
92
The TI is a measure of a drug’s safety , why bro ?
Because a larger value indicates a wide margin between doses that are effective and doses that are toxic.
93
The TI of a drug is determined by ?
Using drug trials and accumulated clinical experience .
94
Clinical usefulness of the therapeutic index usually reveal a ?
Range of effective doses and a different (sometimes overlapping) range of toxic doses .
95
Although high TI values are required for most drugs, some drugs with low therapeutic indices are routinely used to treat serious diseases . (T/F)?
True
———————-
In these cases, the risk of experiencing side effects is not as great as the risk of leaving the disease untreated
96
warfarin, an oral anticoagulant with a (larg/low) therapeutic index, and penicillin, an antimicrobial drug with a (large/low) therapeutic index are examples .
1. Low
2. Large
97
As the dose of warfarin is increased, a greater fraction of the patients respond . (T/F) ?
T
98
for this drug, the desired response is a two- to threefold increase in the international normalized ratio [INR]) until, eventually………
All patients respond.
99
at higher doses of warfarin, anticoagulation resulting in ………. occurs in a (small/wide) percent of patients.
1. hemorrhage
2. small
100
Agents with a low TI (that is, drugs for which dose is critically important) are ?
Drugs for which bioavailability critically alters the therapeutic effects .
101
For drugs such as penicillin, it is safe and common to give doses in excess of that which is minimally required to achieve a desired response without the risk of adverse side effects . (T/F) ?
True
102
Bioavailability does critically alter the therapeutic or clinical effects when you take Penicillin . (T/F) ?
F—>doesn’t
