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Pharmacodynamics Flashcards

1
Q

What is pharmocodynamics?

A

The effects of the drug on the body

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2
Q

When you plot drug dose arithmetically on the x-axis vs drug effect on the y-axis you typically get what type of curve?

A

Hyperbolic curve

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3
Q

When you graph the logarithm of the drug dose vs the response what what type of curve do you get?

A

Sigmoidal curve

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4
Q

What is the Emax of a drug?

A

The maximal effect that can be produced by the drug

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5
Q

What is the ED50 of a drug?

A

The effective dose 50 is the dose of drug that produces 50% of its maximal effect

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6
Q

Which Dose-Response Curve deals with the magnitude of a response varying continuously?

A

Graded Dose-Response curve

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7
Q

What does the Graded Dose-Response curve typically represent?

A

The mean value within a population or a single subject

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8
Q

Which Dose-Response Curve answers whether the response occurs or does not occur along with how many responses there are?

A

Quantal Dose-Response curve

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9
Q

What is the Quantal Dose-Response curve used for?

A

Relates dose of a drug to the frequency of a response within a population

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10
Q

What is a non-cumulative quantal dose response curve?

A

The number or % of individuals responding at a dose of a drug and only at that dose

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11
Q

What is a cumulative quantal dose response curve?

A

Number or % of individuals responding at a dose of a drug and at all doses lower than that dose

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12
Q

What shape does a quantal dose-response curve create?

A

Sigmoidal

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13
Q

What is TD50?

A

The median toxic dose

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14
Q

How do you calculate the Therapeutic Index?

What does it mean if the number is high?

A

1) TD50 / ED50

2) The higher the TI the safer the drug

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15
Q

In regards to a therapeutic window which drugs are considered more dangerous?

A

More narrow therapeutic window

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16
Q

What is drug potency?

A

The amount of drug required to produce a specific pharmacological effect

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17
Q

What is drug potency represented by?

What describes a more potent drug?

A

1) ED50

2) Lower ED50

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18
Q

What is drug efficacy?

A

The maximal pharmacological effect that a drug can produce

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19
Q

What is drug efficacy represented by?

What describes a more efficacious drug?

A

1) Emax

2) Greater Emax

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20
Q

Between drug potency vs drug efficacy which is related to the total number of receptors available to bind a drug?

A

Drug Efficacy

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21
Q

Which bonds are irreversible?

A

Covalent bonds

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22
Q

What is required for drug removal/receptor re-activation for covalent bonds?

A

Re-synthesis of the receptor or enzymatic removal of the drug

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23
Q

Most drugs bind to receptors via what bonds?

A

Non-covalent bonds

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24
Q

The affinity of a drug for a receptor describes?

A

How readily and tightly that drug binds to its receptor

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25
How much drug is needed to produce a response when it has a high affinity for its receptor?
Less drug
26
What is the Kd (equilibrium dissociation constant)?
The drug concentration at which 50% of the drug receptor binding sites are occupied by the drug
27
A drug with a higher affinity for a receptor will have what Kd?
Lower
28
What is drug selectivity?
A property of a drug determined by its affinities at various binding sites
29
What is the Kd ratio?
Kd ratio = Kd, off-target / Kd, target
30
How do more selective drugs compare to less selective drugs?
1) Higher Kd ratio | 2) Fewer adverse effects
31
Intrinsic activity describes what ability of a drug?
To change a receptors function and produce a physiological response upon binding to a receptor
32
Between agonists and antagonists which does not have intrinsic activity?
Antagonists
33
What effect does a full agonist have?
Produces a max pharmacological effect when all receptors are occupied
34
What effect does an inverse agonist have?
Produces an effect opposite to a full or partial agonist by decreasing receptor signaling
35
Partial agonists and full agonists at the same receptor will differ in what way?
The Emax of the partial will be lower
36
What is pharmacologic antagonism?
Action at the same receptor as endogenous ligands or agonist drugs
37
What is chemical antagonism?
When chemical antagonist makes the other drug unavailable
38
What is physiological antagonism?
Occurs between endogenous pathways regulated by different receptors
39
What do competitive antagonists compete with?
Endogenous chemicals or agonist drugs for the same receptor
40
Which non-competitive antagonist binds to and occludes the agonist site on the receptor by forming covalent bonds?
Irreversible antagonists
41
Which non-competitive antagonist binds to a site other than the agonist site to prevent or reduce agonist binding of the receptor?
Allosteric antagonists
42
Which pharmacologic antagonist can be displaced from the receptor by other drugs (effects are surmountable)?
Competitive antagonists
43
What effect does a competitive antagonist have on a dose-response curve?
Agonist EC50 increases and the Emax does not change
44
What effect does a noncompetitive antagonist have on a dose-response curve?
Agonist Emax decreases and the EC50 does not change
45
When an agonist activates a GPCR this promotes Gα protein to release? This allows the entry of what?
1) GDP | 2) GTP
46
In what state does the G protein regulate the activity of an effector enzyme or ion channel? How is the signal terminated?
1) In the GTP-bound state (Gα-GTP) | 2) Hydrolysis of GTP by α subunit
47
What is the target and action of Gs proteins?
1) Adenylyl cyclase | 2) Activation
48
What is the target and action of Gi proteins?
1) Adenylyl cyclase | 2) Inhibition
49
What is the target and action of Gq proteins?
1) PLC | 2) Activation
50
What is the target and action of G12/13 proteins?
1) Rho GTPases | 2) Cytoskeletal rearrangements
51
The repeated or prolonged exposure of cells to agonists favors the delivery of internalized receptors to? This promotes?
1) Lysosomes | 2) Receptor down-regulation rather than resensitization
52
What is the role of phosphodiesterase?
It degrades cAMP
53
When JAKs are activated what do they do?
Phosphorylate STAT molecules so that STAT dimers travel to nucleus and regulate transcription
54
What effect does EGF molecules have upon binding to receptor tyrosine kinases (RTKs)?
Activates it
55
How does the RAS GTPase become activated?
1) Adaptor protein binds to phosphorylated tyrosine in cytoplasmic side of RTK 2) Ras activating protein binds to adaptor protein to activate Ras GTPase
56
What mutation is found in 90% of pancreatic adenocarcinomas? What mutation is found in 70% of melanomas?
1) Point mutation in Ras | 2) Point mutation in Raf
57
What type of drugs inhibit upregulated GF signaling? Examples?
1) Targeted anticancer drugs | 2) Monoclonal Abs to GF receptors and multikinase inhibitors
58
What are ligand-activated transcription factors that modulate gene expression? The ligands are what type of molecules?
1) Nuclear receptors | 2) Lipophilic
59
During glucocorticoid action, what protein binds to the receptor in the absence of the hormone and presents folding into the active conformation of the receptor?
hsp90
60
What ion channel is a target of verapamil?
L-Type Calcium channel
61
What does verapamil act on in a patient with atrial and supraventricular arrhythmias? What effect does it have?
1) SA node and AV node | 2) Decreases HR in SA node and decreases AV conductivity
62
What does verapamil act on in a patient with Angina pectoris? What effect does it have?
1) Cardiomyocyte | 2) Decreased contractility and O2 demand
63
What does verapamil act on in a patient with Hypertension? What effect does it have?
1) Vascular smooth muscle | 2) Relaxation
64
The receptors for growth factors are often?
Receptor tyrosine kinases
65
Inhibition of phosphodiesterase would have what effect on protein kinase A?
Increase its activity
66
When do nuclear receptor ligands produce their effects?
After a lag period of several hours or days
67
What is activated as a result of binding of interferon, interleukins, leptins, and erythropoietin to a cognate receptor?
Cytosolic protein kinases
68
What reduces the level of PIP2?
Gαq

SBL Week 1 (7 decks)

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