L9-10 Pharmacokinetics Flashcards
1
Q
Drug effects depend on
A
Mechanism of action
Physiochemical properties of drugs
Concentration
2
Q
What are the physiochemical properties of drugs
A
Affinity
Efficacy
Potency
3
Q
What are the four elements which affect drug concentration
A
Absorption
Distribution
Metabolism
Excretion
4
Q
Bulk flow of drug uses what
A
The CV system
5
Q
4 methods of drug movement across cell membranes
A
Simple diffusion
Diffusion through aqauporins
Carrier
Pinocytosis
6
Q
What are the physiochemical properties of the drugs
A
Lipid solubility
Diffusivity
7
Q
What constant can be used to quantify lipid solubility
A
Partition coefficient
8
Q
What constant can be used to quantify diffusivity
A
Diffusion coefficient
9
Q
What type of molecules dissolve freely in lipids and penetrate cell membranes freely
A
Lipid soluble
10
Q
What would the effect of using a lipid soluble molecule on rate of absoption from gut be
A
Increase
11
Q
What would the effect of using a lipid soluble molecule on penetration of the brain and other tissues
A
Increase
12
Q
What would the effect of using a lipid soluble molecule on renal elimination
A
Increase
13
Q
What is is one of the most important determinants for pharmacokinetic characteristics of the drug
A
Lipid solubility
14
Q
Describe intravenous administration
When might it be used
A
Injection straight into the plasma
In emergencies
15
Q
What drugs may need to be administered intra muscularly
A
Drugs that would be at high risk of being metabolised in the gut
16
Q
What types of drugs may be at high risk of being destroyed in the gut
A
Peptides
17
Q
Give an example of a peptide drug
A
Insulin
18
Q
What does intrathecal inject into
A
Direct into the CSF
19
Q
Give an example of when intrathecal admin. may be used
A
During labour to administer local anasthetics
20
Q
Define bioavailability
A
How much of the injected drug will make it into the plasma
21
Q
What must be overcome in the stomach
A
Low pH
22
Q
What is the portal system, what is the danger if drugs enter
A
Involving the liver
Drugs would be metabolised by the liver
23
Q
What can be controlled with a drug in tablet form
A
The rate at which the active form of the drug is liberated from the tablet
24
Q
When may the oral route be unsuitable
A
When vomitting
GI problems - ulceration
Young children may find it hard to swallow
25
If the drug target was the GI tract what would be the favoured method of administration
Rectal route
26
What is usually the difference between cheaper and more expensive over the counter drugs
Particle size - tends to be larger with cheaper drugs
27
What is percutaneous administration
Absoprtion through the skin
28
Example of a drug that is adminstered percutaneously
Nicotine via patches
29
What is the problem with percutaneous administration
Skin is highly impermeable
| Drug would need to have a high lipid solubility
30
What would the targets of drugs be that were adminsistered percutaneously
Nuclear receptors
31
example of a type of drug that would be administered percuansouslt
Hormone
32
What two classes of drug are administered by inhalation
General anasthetics and drugs which target the lungs
33
What sort of molecules would cross the placenta
lipophilic (soluble in lipids)
34
Most drugs are weak X and X
Acids and bases
35
Difference between a weak and strong acid
Strong - fully dissociate
| Weak - partially dissociate
36
Describe the dissociation for a weak acid
HA <==> A- + H+
37
What does pKa represent
The pH at which 50% of the acid is in its disociated form
38
State the Henderson-Hasslebach equation
pKa = pH + log (HA/A-)
39
What can be said about weak acids at a low pH
They will be undissociated
40
What can be said about weak acids at a high pH
They will be dissociated
41
pKa of aspirin
3.5
42
Aspirin has a pKa of 3.5, state what will happen in the following
Gastric juices at pH 3
Plasma at pH 7.4
Urine at pH 8
gastric juices, pH low therefore undisociated and able to move freely across the membranes
Plasma pH is higher therfore more will dissociated
In urine pH much higher therfore lots dissociated and it is trapped
43
How can the weak acids become trapped
Undissoicated HA form is non polar so can diffuses across the membrane
Once dissociated both A- and H= have charge, so these are not able to cross the membrane
44
What can be used to treat aspirin poisoning
Increasing the plasma pH by adding HCO3-, weakly acidic drugs are drawn out of the CNS into the plasma where they become trapped
45
Two types of carrier mediated transport
```
Solute carrier (SLC) transport
ATP binding cassettes (ABC) transporters
```
46
SLC transport is
Passive
47
ABC transport is
Active
48
Two consideration to consider for rate at which drug is able to be transported across the cell membrane
Number of channels in the membrane
| MAX rate that these channels are able to function at
49
What two considerations must be made for normal physioligcal fucntion if a large ammount of drug has to be transported across a membrane
Build up on one side if rate is slow
| Impact on transport of the endogenous drugs
50
What is OCT1
Organic cation transporter 1
51
What is metformine
Drug used to treat type 2 diabetes
52
What do genetic variants of OCT1 show when treated with metformin
Different response effects due to single nucleotide polymorphisms (SNPs)
53
4 major body compartments
ECF
ICF
Transcellular
Fat
54
3 compartments of the ECF
Plasma
Interstitial fluid
Lymph
55
Conc of plasma to b.w.
4.5%
56
Two things that determine the distribution of a drug
Permeability and lipid solubility
57
What compartment are non polar drugs able to enter easily
Fat compartment
58
Why does drug entering fat cause problems for people with varying body masses
Ammount of drug entering the fat compartment can vary so concentration of drug in the plasma will vary also
59
What protects the fetus
Placenta
60
What prevents the CNS from drugs
bbb
61
What type of cell junction are involved in the formation of the blood brain barrier
Tight junctions between endothelial cells
62
What is the BBB impermeable to
Impermeable to H20 soluble molecules
63
Give an example of two substances that the BBB would be impermeable to
Peptides, antibiotics
64
What type of molecules are able to cross the BBB, give two examples
Lipid soluble molecules
| Ethanol and caffine
65
What happens to the BBB during inflammation, what disease does this occur in and how may it be treated
Tight junctions become leaky
E.g. in meningitus
Can treat with IV penicillin ==> able to pass through the BBB due to the leaky tight junctions
66
Define the chemoreceptor trigger zone
An area of the medulla that recieves inputs from blood borne drugs and hormones and is able to initiate vomitting
67
What NT has receptors in the chemoreceptor tirgger zone
Dopamine
68
What extra precaution must be taken when treating Parkinsons with dopamine
Dopamine may also be an agonist in the chemoR trigger zone
Should be given with a dopamine antagonist which is also not able to cross the BBB and therefore is unable to cause vomitting
69
Albumin is what? What is it able to do?
Plasma protein
| May bind to drugs
70
Drugs that are bound to albumin are not
Filtered
71
What is the binding capacity of albumin
1.2mmol
72
What is the affect of albumin binding to a drug
It would reduce the concentration of free drug in the plasma
73
What must be taken in consideration when a high concentration of drug is required for the response but plasma protein binding occurs
If binding occurs then won't be as high conc of free drug in the blood ==> response may not be seen
74
What would possibly be the implications if a person was taking more than drug which is known to bind to plasma proteins
One drug will outcompete and displace the other from binding causing the concentrations of drug in the blood to vary dramatically
75
Issues with prescribing a drug to someone with low body fat
Effects can be longer lasting as less is partitioned into the fat compartment
Drug concentration reaching target very high ==> as no reservoir to mop up the drug
76
Phase 1 reaction anabolic or catabolic
Catabolic
77
What does a phase 1 reaction produce
More reactive compounds
78
Phase II reaction anabolic or catabolic
Anabolic
79
What does a phase 2 reaction involve
Conjugation to produce more inactive compounds
80
Example of a microsomal enxxyme found in the liver
Cytochrome P450s
Alcohol dehydrogenase
MAO
81
What must happen in the liver in order for the drug to be metabolised
It must cross the plasma membrane
82
What are prodrugs
Drugs which only become active once they have been metabolised
83
What two things govern the rate of enzymatic metabolism
Ammount of enzyme
| The max rate the enzymes are able to function at
84
Increasing the ammount of enzyme present is known as
Induction
85
What is the knock on effect of adding more enzyme - how would this effect a second dose
Drug is being broken down more efficiently so a dose of the same concentration would have a decreased effect
86
If the drug is able to combine with bile what is avoided
Metabolism
87
What reactions occur during the phase one reaction of aspirin
```
Oxidation
Hydroxylation
Dealkylation
Deamination
Hydrolysis
```
88
State the 3 types of products in the elimination of aspirin
Drug
Derivative
Conjugate
89
State the 3 products in the elimination of aspirin
Aspirin
Salicylic acid
Glucuronide
90
What is the type of reaction aspirin occurs during its phase II reaction
Conjugation
91
Why is paracetamol toxic when overdose taken
During phase I reaction a highly toxic product to the liver is produced
92
Over how many genes for cytochrome p450 enzymes
Over 57
93
What are the individual variations in P450 enzymes
Single nucleotide polymorphisms
94
What is the effect of different isoforms of P450 enzymes
They react with different drugs
95
IA2 is a
Inducer of P450 drug metabolism
96
3 examples of IA2
Brocoli
Brussel sprouts
Tobacco
97
Glomerular filtration will remove drugs with a
Low Mr
98
Will drugs bound to albumin be filtered
No - Mr of 68'000
99
What is active tubular secretion
Transport of drugs directly into the urine
100
How do liophilic molecules get excreted
Passive diffusion across the plasma membrane
101
Describe how penicillin is cleared
Cleared on a single pass
102
Describe how diazepan is cleared from the body
Cleared very slowly
103
What are two other methods for elimination of drugs
GI excretion - bound up by food
| Expired by the lungs
104
Time course of clearance follows what
A mono exponential decay
105
Time course of clearance is determined by
Metabolism and excretion
106
Is half life always constant for the same drug
Yes
107
What is half life
Time taken for the concentration of drug to fall by half
