Pharmokinetics 1 Flashcards
(96 cards)
1
Q
How do all drugs exert their effects?
A
By binding to a target
2
Q
What are the majority of drug targets?
A
Proteins, with some exceptions
3
Q
Give an example of an exception to drug targets being proteins
A
Some antimicrobial and antitumour drugs bind DNA
4
Q
What do must drugs bind with?
A
Receptors
5
Q
Is drug binding to receptors reversible?
A
Usually
6
Q
What is binding of drugs to receptors governed by?
A
Association and dissociation rates
7
Q
Give 7 targets for drugs
A
Enzymes GPCRs Ion channels Nuclear hormone receptors Integrins Other receptors
8
Q
What % of drug targets are enzymes?
A
47%
9
Q
What % of drug targets are GPCRs?
A
30%
10
Q
What % of drug targets are ion channels?
A
7%
11
Q
What % of drug targets are transporters?
A
4%
12
Q
What % of drug targets are nuclear hormone receptors?
A
4%
13
Q
What % of drug targets are other receptors?
A
4%
14
Q
What % of drug targets are integrins?
A
1%
15
Q
What is critical in determining drug action?
A
The concentration of drug molecules around receptors
16
Q
What do drugs of equivalent molar concentrations have?
A
The same concentration of drug molecules
17
Q
Do drugs of equivalent concentrations by weight have the same concentration of drug molecules?
A
They may not
18
Q
How much does 1 mole contain?
A
6x10^23
19
Q
What does 1 molar solution contain?
A
1 mole in 1 litre
20
Q
How do you calculate grams per litre?
A
Molecular weight x molarity
21
Q
What do agonists do?
A
Bind to receptors and cause a response
22
Q
What do agonists have?
A
Both affinity and efficacy
23
Q
What do antagonists do?
A
Bind to receptors, but do not cause a response
24
Q
What do antagonists have?
A
Affinity only
25
What is affinity?
The likelihood of a ligand binding to its target
26
What is efficacy?
The likelihood of activation
27
How is binding information often obtained?
By the binding of a radioligand
28
What is a radioligand?
A radioactive version of the ligand
29
What is Bmax?
The maximum binding capacity
30
What does Bmax give?
Information about the number of receptors
31
What is Kd?
The dissociation constant
32
What is Kd a measure of?
Affinity
33
How is Kd worked out?
It is the concentration needed for 50% occupancy
34
What does a lower Kd value relate to?
A higher affinity
35
On what scale is [drug] usually shown
Logarithmic
36
Where in concentration response curves used?
In measured in a response in cells/tissues
37
When are dose response curve used?
When measuring a response in a whole animal
38
What is Emax?
The maximum response
39
What is EC 50 ?
The effective concentration giving 50% of the maximal response
40
What is EC 50 a measure of?
Potency
41
What is potency?
A combination of both affinity and efficacy
42
What governs potency?
The number of receptors
43
In what terms is efficacy measured?
Relative- no absolute scale
44
What may agonists with different Emax value have?
Different efficancy
45
Do agonists with the same Emax values have identical efficacy?
Not always
46
Why may two drugs with the same Emax values not have the same efficacy?
They may differ in affinity, meaning that the relationship between occupancy and response will be different- one may be more able to convert binding into function
47
What is the treatment goal is asthma?
To activate ß2-adrenoceptors to relax the airways
48
What is the problem with activating ß-adrenoceptors to treat asthma?
There are ß-adrenoceptors elsewhere in the body
49
Give an example of where ß-adrenoreceptors are found elsewhere in the body?
ß1 in the heart increase the force and rate of contraction
50
What is salbutamol?
A ß2-adrenoagonist
51
What is the Kd of salbutamol?
20µM for ß1
| 1µM for ß2
52
What is the result of the lower Kd for ß2?
It has a higher affinity
53
Why can salbutamol be used in treatment of asthma?
Because of the higher affinity for ß2-receptors, as well as ß2 selective efficacy and route of administration- this limits ß1 activation and side effects
54
What is the route of administration of salbutamol in the treatment of asthma?
Oral spray
55
What is salmeterol?
A longer acting ß2-adrenagonist than salbutamol
56
How does salmeterol differ from salbutamol?
It has no selective efficacy
57
How does salmeterol prevent ß1 activation and side effects?
Purely through differences in affinity
58
What is the Kd of salmeterol?
1900nm for ß1
| 0.55nm for ß2
59
What will less than 100% receptor occupancy give in some cases?
100% response
60
What is true when 100% receptor occupancy gives 100% response?
EC50 is less than Kd
61
Describe the relationship between receptor occupancy and response?
Non-linear
62
What is the relationship between receptor occupancy and response influenced by?
Both the transduction system/amplification produced by second messengers, and the properties of the tissue
63
What is meant by spare receptors?
Some tissues have more receptors than required to produce a maximal response
64
What is the advantage of spare receptors?
It increases sensitivity, allowing for responses at low concentrations of agonist
65
What does number of receptors have an effect on?
Potency
66
What is a partial agonist?
A drug that cannot produce a maximal effect, even with full receptor occupancy
67
How can a partial agonist be identified?
By comparing the ability of different agonist to evoke responses in a tissue
68
What is the EC50 of a partial agonist equal to?
Its Kd
69
What is the potency of a drug dependent on?
Both its affinity and efficacy
70
Are partial agonists more or less potent than full agonists?
Can be either
71
Is a partial agonist always so?
No
72
What does wether an agonist is partial or not depend on?
The tissue and the biological response
73
What are opioids used for?
Pain relief Recreationally
74
What can opioid cause?
Respiratory depression, leading to death
75
How do opioids act?
Primarily through the µ-opioid receptor (GPRC)
76
How do morphine and buprenorphine differ?
Morphine is a full agonist of the receptor
| Buprenorphine is a partial agonist, with a higher affinity but lower efficacy
77
Why is buprenorphines high affinity and low efficacy advantageous?
If it provides adequate pain control it is preferable, as there is less respiratory depression
78
What are the types of antagonist?
Reversible competitive
Irreversible competitive
Non-competitive
79
What is the most common form of antagonist?
Reversible competitive
80
Where is reversible competitive antagonism important?
In therapeutics
81
What does reversible competitive antagonism rely on?
A dynamic equilibrium between ligands and receptors
82
What is IC50?
The concentration of antagonist giving 50% occupancy
83
How can reversible competitive antagonists be overcome?
By high concentrations of agonists
84
Give a therapeutic example of a reversible competitive antagonist?
Naloxone
85
What is naloxone?
A high affinity, competitive antagonist of µ-opioid receptors
86
What is naloxone used to do?
Reverse opioid mediated respiratory depression
87
Why can naloxone be used to reverse opioid mediated respiratory depression?
Its high affinity means it will compete effectively with other opioids for receptors
88
When does irreversible competitive antagonism occur?
When the antagonist dissociates slowly, or not at all
89
What do irreversible competitive antagonisms cause to the concentration-reponse curve?
A permanent shift to the right
90
What do irreversible competitive antagonists do at high concentrations?
Suppress the maximal response
91
Why do irreversible competitive antagonists suppress the maximal response at higher concentrations?
As spare receptors are filled by the antagonist, not leaving enough receptors free to illicit a maximal response
92
Give a therapeutic example of irreversible competitive antagonism?
Phenoxybenzamine
93
What is Phenoxybenzamine?
A non-selective irreversible α1-adrenoreceptor blocker
94
Where is Phenoxybenzamine used?
In hypertension episodes in pheochromocytoma
95
What is pheochromocytoma?
A tumour of the adrenal gland, which causes excessive NA/Adrenaline secretion leading to vasoconstriction
96
What is non-competitive antagonism?
The allosteric binding of an antagonist to a receptor (not the ligand binding site)
