Pharmacology Flashcards

(57 cards)

1
Q

What is signal transduction?

A

When a chemical messenger is released from one cell and binds to a receptor on another cell to initiate a response within it

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2
Q

What does signal transduction allow?

A

Coordination

Integration

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3
Q

How do chemical messengers target specific cells and only produce a response within these cells? What does this allow?

A

They receptors on these specific cells will have a complementary shape with the chemical messenger

Specificity, which means that all cells won’t carry out the same function but rather specialised functions

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4
Q

Can two cells with the same receptor carry out different responses when the chemical messenger binds to them?

A

Yes

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5
Q

Can cells have several different receptors for the same chemical messenger? Why?

A

Yes, this means they can trigger several different responses within the same cell

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6
Q

What classification of chemical messengers are able to pass through the phospholipid bilayer?

A

Hydrophobic/Lipophillic

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7
Q

Where are the receptors for hydrophobic messenger founds?

A

Within the cell

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8
Q

How are hydrophobic messengers transported through the blood?

A

Bound to a protein in the plasma. When the messenger passes a cell with the appropriate intracellular receptor, their affinity for this binding protein will decrease, causing them to unbind and move through the phospholipid bilayer to bind to it

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9
Q

Name two hydrophobic messengers

A

Steroid hormones

Nitric oxide

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10
Q

What are steroid hormones?

A

Hydrophobic messenger

Bind to intracellular receptors found on DNA. When they bind to the DNA they can alter the rate of gene transcription

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11
Q

What is nitric oxide?

A

Hydrophobic messenger

Binds to soluble guanlyl cyclase, which is a type of intracellular receptor. When it binds to this receptor it will generate cGMP, which is a phosphate that acts as a second messenger and regulates cell activity

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12
Q

What are second messengers?

A

Chemical messengers that are created after the extracellular chemical messenger binds to its receptor. These messengers are involved in initiating a response within the cell. They apply to both extracellular and intracellular responses.

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13
Q

What chemical messengers are unable to pass through the phospholipid bilayer?

A

Hydrophilic/Lipohobic

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14
Q

Where are the receptors of hydrophilic chemical messengers found?

A

Surface receptors in the plasma membrane of the cell

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15
Q

What are the four types of surface receptors?

A

Ionotropic receptor

Receptor kinases

Non-receptor tyrosine kinases

G-protein coupled receptor

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16
Q

What are ionotropic surface receptors? How do they work?

A

Recptors which are part of an ion channel

When their chemical messenger binds, it will result in the ion channel opening or closing, which will affect the ion concentration inside and outside the cell (membrane potential). This will result in a cellular response, which is normally to stimulate fast IPSP and EPSP

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17
Q

What are receptor kinases? How do they work?

A

Receptors which have an enzyme (tyrosine kinase ) physically built into their structure.

When their chemical messenger binds, the tyrosine kinase is either activated or inactivated, which either stimulates or inhibits tyrosine kinase from phosphorylating its substrate . This results in a cellular response, which is usually to stimulate proliferation or differentiation

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18
Q

What are non-receptor tyrosine kinase receptors? What type of enzyme is involved? How do they work?

A

Receptors don’t have the kinase enzyme physically built into its structure but instead the enzyme is bound onto it.

JAK kinase

When their chemical messenger binds, the JAK kinase is either activated or inactivated, which either stimulates or inhibits tyrosine kinase from phosphorylating its substrate . This results in a cellular response, which usually affects protein synthesis

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19
Q

What are G-protein coupled receptors? How do they work?

A

Receptor that have a G-protein attached to them.

When their chemical messenger binds, a subunit of the G-protein is displaced across the membrane and will bind to another protein. This stimulates a cellular response

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20
Q

Describe the structure of G-proteins

A

Made up of seven transmembrane spanning segments. Sometimes segments are seen in the plasma membrane

Explains why G-proteins are referred to as 7TM

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21
Q

Describe the mechanism of G-protein coupled receptor which is coupled to adenylyl cyclase

A

When the chemical messenger binds, activates G-protein.

Results in the alpha-subunit of the G-protein displacing itself across the membrane so that it can bind to the enzyme, adenylyl cyclase.

When the alpha-subunit is bound to adenyl cyclase, produces a second messenger, cAMP

cAMP regulates the activity go another enzyme, PKA.

cAMP will activate PKA, which causes it to phosphorylate a protein as it is a kinase enzyme

The phosphorylated protein can cause a cellular response, which can vary

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22
Q

Describe the mechanism of G-protein coupled receptor which is coupled to phospholipase C

A

When the chemical messenger binds, activates G-protein.

Results in the alpha-subunit of the G-protein displacing itself across the membrane so that it can bind to the enzyme, phospholipase C

When the alpha-subunit is bound to adenyl cyclase, produces two second messenger, IP3 and DAG

IP3 and DAG both activate PKC, but IP3 does it out indirectly and DAG carries it out directly

IP3 has to release Ca2+ ions from the endoplasmic reticulum in order to activate PKC

PKC will phosphorylate a protein, as it is a kinase

The phosphorylated protein can cause a cellular response, which can vary

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23
Q

Why does double activation of PKC occur?

A

Two secondary messengers activate it

24
Q

What secondary messengers are associated with phospholipase C?

25
What secondary messengers are associated with adenlyl cyclase?
cAMP
26
What does cAMP activate?
PKA
27
What does DAP and IP3 activate?
PKC
28
Apart from enzymes, what can G-proteins also be coupled to?
Ion channels This doesn't mean that the G-proteins are ionotropic as they are coupled with it not part of it.
29
What cellular response is usually evoked when G-proteins are coupled to ion channels?
Slow EPSPs and IPSPs
30
What ion is common secondary messenger?
Ca
31
Name the three sources of Ca
Endoplasmic reticulum - release Ca through the action of IP3 Voltage-gated or ligand-gated calcium channels Inhibit-on of calcium transported out of the cell
32
What two responses can Ca cause in the cell?
Directly affect target protein (like PKC) Bind to calmodulin, which is a protein that activated other target proteins
33
What is a drug?
A chemical agent that affects a biological system by binding to receptors
34
What happens to the size of the response, if we increase the concentration of drug molecules?
A bigger response, as tan increased number of molecules are able to bind to a receptor However, there is a limited number of receptors. This means that once we have reached a big enough concentration of drug molecules, all the receptors are saturated with a drug molecule and we have reached a maximum response
35
What happens if we increase the number of drug molecules at the maximum response?
Nothing, no more receptors for them to bind to
36
Why is that when we plot a concentration-response graph, a curve is drawn and not a straight line?
Law of random bumping, which means that the drug molecules are more likely to bump into a vacant receptor when the concentration of the drug is low, as there is less competition
37
What type of curve do we get when we draw a graph, where the x-axis is the log of the drug concentration and the y-axis is the response? What value can we obtain from these graphs
Sigmoid EC50
38
What is the EC50?
The log of the drug concentration where we reach half the maximal response
39
What does the EC50 help us to quantify?
The affinity of the drug to the receptor
40
What does it mean if we have a low EC50 value?
Indicates a high affinity between the drug and the receptor, as less drug is needed to reach half the maximal response
41
What direction would the sigmoid curve shift to when the drug has a higher affinity for its receptor?
To the left, which makes sense as this means that its EC50 value will be less
42
What direction would the sigmoid curve shift to when the drug has a lower affinity for its receptor?
To the right, which makes sense as this means that its EC50 value will be greater
43
What does it mean if we have a low EC50 value?
Indicates a low affinity between the drug and the receptor, as more drug is needed to reach half the maximal response
44
What does efficacy mean?
How good the drug is in activating the receptor
45
What does it mean if a drug has a high efficacy?
They fully activate the receptor
46
What does it mean if a drug has a low efficacy?
They partially activate the receptor
47
What is the difference between drugs with a low efficacy and a high efficacy on a graph, where the x-axis is the log of the drug concentration and the y-axis is the response?
The drug with the low efficacy will have a maximum response level which is half the maximum response level of the the drug that has a high efficacy
48
What correlated with efficacy?
Maximum response
49
What two factors affect the response of a drug?
Efficacy Affinity
50
What are full antagonists?
Drugs with a high affinity and a high efficacy
51
What are partial antagonists?
Drugs with a high affinity and a low efficacy
52
What are antagonists?
Drugs with a high affinity and no efficacy
53
What are agonists?
Molecules which bind to the receptor and evoke a normal response
54
What are anatoginists?
Molecules which bind to the receptor and block the normal action of the receptor.
55
Why can anatgonists be useful?
They can block chemical messengers within the body that bind to a receptor and stimulate a harmful response
56
How do antagonists effect a graph, where the x-axis is the log of the drug concentration and the y-axis is the response?
The curve will shift to the right, as more drug concentration is required to reach the maximal response and the shifted curve will have a higher EC50 value This makes sense as the antagonists will block the binding sites and prevent the drug molecules from finding vaccine receptors, making it a longer process for them to find them all
57
Why is selectivity of drugs useful?
We can select agonists that will enhance a good effect and select antagonists that will block a bad effect It can also be useful for producing selective therapeutic effects, without side effects