1
Q
What activates the receptor to signal as a direct result of binding to it?
A
Agonists
2
Q
What type of agonist gives a 100% response?
A
Full agonist
3
Q
What type of agonist produces a lower response at full receptor occupancy than a full agonist?
A
Partial agonist
4
Q
Do partial agonists or full agonists have higher efficacy?
A
Full agonists have higher efficacy than partial.
5
Q
Do partial agonists produce a response when alone?
A
Yes
6
Q
In the presence of a full agonist, how does a partial agonist act?
A
Like a competitive inhibitor and blocks full agonist - therefore EC50 increases, Emax same (slope moved to the right)
7
Q
Does an allosteric agonist bind at the same site as an endogenous agonist?
A
No, binds to a different site
8
Q
Does an allosteric agonist produce a signal itself?
A
No
9
Q
How does an allosteric agonist impact the effect of an endogenous agonist?
A
Increases the effect of an endogenous agonist allosterically
10
Q
Allosteric modulators _________ effect of endogenous ligands
A
Potentiate
11
Q
How would an allosteric agonist impact the slope of CRC graph?
A
Shift slope of the line to the left because it potentiates the effect of the endogenous ligand
12
Q
How do antagonists interact with receptors?
A
Bind to receptor but do not activate it
13
Q
How do antagonists impact agonists?
A
Interfere with ability of agonist to activate the receptor
14
Q
What are the two types of Pharmacological Antagonists?
A
Competitive and non-competitive
15
Q
How do competitive antagonists bind to the receptor?
A
Bind reversibly to the receptor
16
Q
Can inhibition of a competitive antagonist be overcome? If so, how?
A
Yes, it can be overcome by increasing the concentration of the agonist
17
Q
How do non-competitive antagonists bind to the receptor?
A
Bind irreversibly to the receptor
18
Q
Can inhibition of a non-competitive antagonist be overcome? If so, how?
A
No, it cannot be overcome.
19
Q
E.max is also known as _______________________.
A
Efficacy or maximal effect produced by drug
20
Q
EC50 is the concentration of drug that gives _______ % of max effect
A
50%
21
Q
How does receptor binding affinity impact potency?
A
Increased receptor affinity leads to increased potency
22
Q
Bigger size tablet = ________ potency
A
Less potency
23
Q
Smaller size tablet = _________ potency
A
More potency
24
Q
Higher the EC50, ________ the potency
A
lower
25
What is the Bmax of a drug?
The maximum binding to a receptor. (All receptors are bound)
26
Kd is the conc of the drug at which _______________
Receptor occupancy is 1/2 max
27
The higher the Kd, the ____ the affinity of receptor for its ligand
weaker/lower
28
The lower the Kd, the _____ the affinity of receptor for its ligand
higher
29
How does potency relate to size of pills?
Smaller pill, more potent
## Footnote
Larger pill, less potent
30
What is the potency of a drug?
Expression of the concentration required to reach a 50% occupancy (EC50) or dose (ED50)
31
Height reached by a curve in a Concentration response curve graph indicates what?
Emax
32
Partial agonists showed mixed properties. What does this mean?
Has mixed agonist-antagonist properties
33
How does a partial agonist impact the effect of a full agonist when together?
Reduces effect of full agonist
34
If a partial agonist is given in presence of a full agonist, it will __________ effect of the Full agonist
Reduce/block
35
If a partial agonist is given to a patient who has been taking an agonist, pain may be decreased/increased (pick one). And why exactly?
increased! As the partial agonists fight for receptors with the agonists, the effects become less. That mean the pain goes up.
36
How does a competitive antagonist impact Emax and EC50?
Emax will stay the same
## Footnote
EC50 will be increased
37
How does a competitive antagonist impact CRC graphs?
Causes line on CRC graph to shift right
38
How do non-competitive antagonists impact Emax and EC50?
Emax is decreased due to receptors being blocked
## Footnote
EC50 stays the same
39
What are the 4 groups of antagonistic mechanisms?
PCPP
## Footnote
Pharmacological, Chemical, Physiological, Pharmacokinetic
40
Describe why pilocarpine did not help in this patient?
Pilocarpine did not help because while Pilocarpine is a cholinergic agonist, atropine is a cholinergic antagonist. Competitive pharmacological antagonism is taking place which can be overcome with increased concentration
41
What type of antagonism is this an example of? A positive protein binds to and inactivates Heparin which is a (-) charged anticoagulant.
Chemical antagonism
42
What type of antagonism occurs between endogenous regulatory pathways or agonists acting at different receptors?
Physiologic antagonism
43
glucocorticoids vs insulin; PANS vs SANS are examples of what type of antagonism?
Physiologic antagonism
44
When one drug increases metabolism or elimination of another, what type of antagonism is occurring?
Pharmacokinetic antagonism
45
What are the 3 main mechanisms of therapeutic and adverse effects of drugs?
1. Effects mediated by same mechanism (e.g., BP meds causing low BP).
2. Effects mediated by same receptors in different tissues (e.g., steroids causing multiple other effects in the body).
3. Effects mediated by different receptors.
46
What is the dose at which 50% of individuals exhibit the specified quantal effect?
Median effective dose (ED50).
47
What is the dose required to produce a particular toxic effect in 50% of the population?
Median toxic dose (TD50).
48
What indicates efficacy and what indicates the potential variability of responsiveness among individuals?
Graded DRC indicates efficacy, while Quantal DEC indicates potential variability.
49
Is a wide therapeutic index or narrow therapeutic index safer?
Wider therapeutic index is safer.
50
Safer medications have what type of therapeutic indexes?
Wider therapeutic indexes.
51
What type of therapeutic index do OTC meds usually show?
Wider, safer.
52
What does a narrow therapeutic index usually give a higher chance of?
Bad side effects occurring.
53
What is the range between the minimum toxic dose and the minimum therapeutic dose?
Therapeutic window.
54
What is the therapeutic index a ratio of?
TD50 to ED50.
55
What is the formula for Therapeutic Index (TI)?
TI = TD50/ED50 (toxic dose/effective dose).
56
The higher the Therapeutic Index, the ___________ the drug.
safer.
57
The smaller the therapeutic index, the ___________ the drug.
Less safe.
58
Most receptors for clinically relevant drugs are what?
Proteins.
59
What are the 4 types of drug-receptors/channels discussed?
1. Ligand-gated ion channels.
2. G protein-coupled receptors.
3. Enzyme-linked receptors.
4. Intracellular receptors.
60
Which of the 4 drug receptors discussed are trans-membrane?
Ligand-gated ion channels, G protein-coupled receptors, and Enzyme-linked receptors.
61
Which one of the 4 drug receptors discussed is inside the cell?
Intracellular receptors.
62
What causes a ligand-gated ion channel to open or close?
Binding of a ligand.
63
G protein-coupled receptors (GPCRs) stimulate a ____________ which in turn modulates production of an _________________?
G protein; Intracellular second messenger.
64
What type of receptor proteins' enzyme activity is allosterically regulated by a ligand that binds to a site on the protein's extracellular domain?
Enzyme-linked receptors.
65
A lipid-soluble ligand that crosses the membrane will act on a _______________ receptor?
Intracellular.
66
What are the two types of ion channels?
Ligand-gated and Voltage-gated.
67
For ligand-gated ion channels, drugs often _________ or ________ the actions of natural agonists?
Mimic or block.
68
Give an example of a ligand-gated ion channel.
Nicotinic acetylcholine receptor, Serotonin, GABA, Glutamate.
69
Voltage-gated ion channels do not bind neurotransmitters directly but are controlled by ______________________?
Membrane potential.
70
A calcium channel blocker will act on what type of ion channel?
Voltage-gated ion channel.
71
What are two examples of voltage-gated ion channels?
Na+ and Ca++ channels.
72
Local anesthetics block ________ channels?
Voltage-gated Na+.
73
With G protein coupled receptors, extracellular ligands act by increasing what intracellular effectors?
Intracellular effectors like Gs, GI, Gq.
74
What is the mechanism of action for G-protein coupled receptors?
1. Extracellular ligand binds to GPCRs.
2. Receptor activates GTP-binding protein/G-protein.
3. Activated G protein turns on an effector element which changes the concentration of the intracellular second messenger.
75
What are Gs receptors?
B-adrenergic (B1, B2), Dopamine (D1), Histamine (H2).
76
What is the effector/signaling pathway for Gs?
- Increase adenylyl cyclase -> increase cAMP -> production of PK-A.
77
What are Gi receptors?
Adrenergic (A2), Dopamine (D2), Acetylcholine Muscarinic (M2, M4).
78
What is the effector/signaling pathway for Gi?
Decrease adenylyl cyclase -> decreased cAMP -> open cardiac K+ channels - slows heart rate.
79
What are Gq receptors?
Adrenergic (A1), Acetylcholine (M1, M3, M5), Histamine (H1).
80
What is the effector/signaling pathway for Gq?
- Increase phospholipase C -> increase IP3 (cytoplasmic Ca2+) and diacylglycerol (PKC).
81
Enzyme-linked receptors are polypeptides with an extracellular ______________ and a cytoplasmic ______________?
Hormone-binding domain; Enzyme domain.
82
An insulin receptor linked to tyrosine kinase is an example of what type of receptor?
Enzyme-linked receptor.
83
Anti-cancer drugs act on what type of receptors?
Enzyme-linked receptors.
84
Cytokine receptors are what type of receptors?
Enzyme-linked receptors.
85
Cytokine receptors respond to peptide ligands like?
Growth hormone, Erythropoietin, Interferons.
86
What is the main example discussed of intracellular receptors?
Steroids.
87
What is desensitization?
Desensitization is a decreased response due to continued presence of an agonist.
## Footnote
Called tachyphylaxis.
88
What is the requirement of higher doses of a drug to produce a given response?
Tolerance.
89
If the agonist is removed, will full responsiveness occur with subsequent addition of agonist?
Depends, but not if cells are exposed to the agonist repeatedly or over a more prolonged time period.
90
How does repeated or prolonged agonist exposure impact receptors?
Causes a down-regulation and reduced number of receptors.
91
What can cause upregulation?
If receptor activation is blocked for prolonged periods due to use of antagonists.
92
How are receptors impacted when an antagonist that has been used for an extended period of time is stopped?
Receptors become supersensitive or hypersensitive to stimulation.
93
Why might seizures occur after an alcoholic quits drinking suddenly?
Over-activation of receptors that were once blocked.
Block 09
flashcards
Decks in class (33)
# Cards
-
Epi: Introduction126
-
Mono: Photometry And Radiometry79
-
Pharm: Introduction14
-
Pharm: Pharmodynamics93
-
Mono: Lightness36
-
Mono: Sources and Filters46
-
Epi: Transmission Of Disease90
-
Pharm: Pharmacokinetics 192
-
Pharm: Pharmacokinetics 255
-
Mono: Duplex Retina86
-
Micro: Introduction To Viruses74
-
Micro: dsDNA Viruses134
-
Micro: HepaDNAvirus25
-
Micro: ssDNA viral pathogens14
-
Micro: (+)ssRNA enveloped viruses136
-
Epi: Disease Occurence77
-
pharm: pharmacokinetics 343
-
pharm: pharmacokinetics 461
-
pharm: pharmacokinetics 556
-
micro: naked (+) ssRNA viruses43
-
mono: spatial resolution and summation59
-
mono: spatial vision75
-
mono: clinical implications to CSF39
-
mono: temporal vision59
-
pharm: pharmacogenomics36
-
micro: -ssRNA and -dsRNA viruses122
-
micro: retroviruses and prions36
-
epi: ocular and systemic disease and disorders148
-
Micro: Virus review121
-
Mono: Motion Perception80
-
Mono: Depth Perception51
-
Epi: Epidemiology In Appalachia18
-
Micro: Flora96
