Pharmacokinetics Flashcards
1
Q
What four factors are involved in the study of pharmacokinetics?
A
absorption, distribution, metabolism, and excretion
2
Q
After providing a dose, what 4 things can determine concentration in the blood?
A
- absorption (gi, pH, rate)
- distribution (theoretical)
- elimination (metabolism, excretion, dialysis)
- dosing interval
3
Q
What determines how drug concentration in the blood gets to concentration at the site of action?
A
Distribution
4
Q
What is first order kinetics for drug elimination (excretion/metabolism/dialysis)?
A
It means that a constant FRACTION of drug is removed per unit time NOT a constant AMOUNT of drug.
5
Q
As the concentration of drugs in the plasma decreases, what happens to the Ke in first order kinetics?
A
The elimination rate slows as the concentration of drug decreases because a fraction is removed per unit time
6
Q
What is meant by zero-order kinetics?
A
A constant amount (NOT fraction) of drugs is eliminated per unit time because it is saturable.
7
Q
What are the three common drugs that follow zero-order kinetics?
A
- phenytoin
- ethanol
- salicylates
8
Q
If a drug has a high Km, what does that say about the affinity?
A
low affinity
9
Q
Most enzymes of drug metabolism and physical excretion mechanisms have _____________values of Km and _________ capacity overall.
A
high values of Km (low affinity)
high capacity overall (can clear a wide variety of toxins
10
Q
What kind of dose (oral, topical, IV) will have first order elimination kinetics?
A
oral and IV
11
Q
What is the therapeutic index?
A
The logarithmic concentration of drugs between toxicity and therapeutic benefit
12
Q
For first order kinetics, as the drug concentration increases, the elimination rate (Ke) __________________.
A
increases
13
Q
In a graph of serum concentration (log) over time, the straight terminal segment is called the _____________. What is the slope of this part of the graph?
A
serum decay curve
Slope= -Ke/2.3
14
Q
What are the units of Ke?
A
inverse of time (1/time)
15
Q
In regards to the elimination constant, what does t1/2 equal?
A
T1/2= 0.693/ke
16
Q
The initial drug concentration at t=0 can be used to calculate ________________ if you are given the __________/
A
volume of distribution if you are given the bioavailability
17
Q
If a graph of serum concentration over time doesn’t show an initial rise in serum concentration, what can be said about how the dose was administered?
A
It means that there was no absorption phase so the dose must have been given via IV
18
Q
With IV administration, what are the two phases of decay?
Which is slower?
A
- distribution phase- where it leaves serum to enter tissue (stores, target tissue, etc)
- elimination phase (*slower phase)
19
Q
If you extrapolate the serum decay line to the Y-itercept, what value would it tell you?
A
Concentration at time zero which is equal to Dose/Vd
20
Q
What is an example of a time when Vd would be larger than total body volume?
A
When the drug can distribute into non-plasma compartments like fat
21
Q
For zero order kinetics, elimination is best characterized by ____ and ____ rather than ____ and ____.
A
Km and Vmax rather than Vd and CL
22
Q
If you increase the dose for a substance following zero order kinetics, what happens to fractional clearance and half life?
A
The fractional clearance decreases and the apparent half life increases
23
Q
What happens to the steady state concentration if you increase the dose?
A
It will increase because the elimination rate will increase as well
24
Q
What is bioavailability?
A
the fractional amount of a dose that gets into the blood (bound or unbound)
25
What is the bioavailability of a drug administered via IV?
F=1
26
If a drug is administered orally, what two factors determine the bioavailability?
1. amount absorbed
| 2. amount metabolized by first pass in liver
27
What does Vd help you determine?
Loading Dose
28
If you want to achieve a certain serum concentration, what equation is used for loading dose?
conc = (dosexF)/Vd
29
What is the purpose of administering a loading dose?
to achieve a serum concentration quickly and a therapeutic concentration rapidly
30
If you do not issue a loading dose, how long would it take to achieve the appropriate steady state concentration?
4-5 times the elimination half life
31
What time frame should loading doses be administered over?
3-5 minutes
32
What is clearance?
| What are the units?
the amount of blood (or fluid) from which ALL drug is removed per unit time
ml/min
33
What are the three main types of clearance?
blood, plasma, serum
34
What factor is important for loading dose? What factor is most important for maintenance dose?
Loading- Vd
| Maintenance- CL
35
What is the equation for maintenance of steady state concentration?
Conc= (Fxdose)/(intervalxCL)
36
What three factors can influence maintenance of the steady state concentration of a drug?
1. Bioavailability
2. Dose/dose interval
3. CL
37
The more frequent a dosing interval the _________ fluctuation in steady state concentration.
less
38
What is half-life? How is it calculated?
t1/2= (0.693Vd)/CL
39
What happens to the number of half lifes to reach steady state when how often the drug is given is changed?
Dose?
Elimination pattern?
The half life stays the same in all situations at about 4-5 half lives to reach steady state
40
What can be altered to optimize drug absorption at the appropriate site?
1. Drug design
2. Formulation
3. delivery of drugs
41
What five things are absorption dependent on?
1. blood flow
2. chemical nature of the drug
3. formulation
4. disease-induced changes in perfusion
5. injury to absorption site
42
Ambient changes to pH that favor _____ species will promote absorption
unionized
43
Weak acids will be more permeant at ____ pH so they are absorbed better in the _________.
low; stomach
44
Weak bases are more permeant at _____ pH so they will be better absorbed in the _____
high; intestines
45
Where will MOST of weak acids be absorbed?
despite the fact that they are better absorbed in the stomach, most weak acids will be absorbed in the intestines because they have a longer transit time and surface area
46
Where will the charged form of a drug be trapped when working with a weak base?
It will be trapped on the more acidic side
47
What is the first pass effect?
Drugs that are absorbed in the GI tract go to the liver via portal system before entering circulation. The liver will metabolize a large fraction of the drug
48
What are the three most important aspects of drug absorption?
1. Lag time (formulation, route, gastric emptying)
2. Extent of absorption (bioavailability)
3. Rate of absorption
49
What five factors determine the bioavailability of a drug?
1. Product formulation
2. Intestinal transit time
3. Drug interactions
4. Food intake
5. First pass effect
50
What factors affect the first pass effect?
1. blood flow to the liver
| 2. capacity of the liver to metabolize the drug
51
What determines the rate of absorption?
1. Product formulation
2. Drug interactions
3. GI physio, path
52
What five factors affect distribution?
1. Active transport into tissues
2. Chemical properties (lipid soluble, size, ions)
3. Binding to plasma proteins
4. Uptake into sinks (fat, bone, etc)
5. Tissue perfusion
53
Where will MOST of weak acids be absorbed?
despite the fact that they are better absorbed in the stomach, most weak acids will be absorbed in the intestines because they have a longer transit time and surface area
54
Where will the charged form of a drug be trapped when working with a weak base?
It will be trapped on the more acidic side
55
What is the first pass effect?
Drugs that are absorbed in the GI tract go to the liver via portal system before entering circulation. The liver will metabolize a large fraction of the drug
56
What are the three most important aspects of drug absorption?
1. Lag time (formulation, route, gastric emptying)
2. Extent of absorption (bioavailability)
3. Rate of absorption
57
What five factors determine the bioavailability of a drug?
1. Product formulation
2. Intestinal transit time
3. Drug interactions
4. Food intake
5. First pass effect
58
What factors affect the first pass effect?
1. blood flow to the liver
| 2. capacity of the liver to metabolize the drug
59
What five factors affect distribution?
1. Active transport into tissues
2. Chemical properties (lipid soluble, size, ions)
3. Binding to plasma proteins
4. Uptake into sinks (fat, bone, etc)
5. Tissue perfusion
60
Where does most drug metabolism occur?
Liver
61
What accounts for 1/3 of phase one metabolism?
Cyp3A4
62
What is the predominant enzyme for phase I drug metabolism?
p450s
63
P450s have a ______ substrate range and can catalyze_________ reactions.
very broad; many
64
Where will MOST of weak acids be absorbed?
despite the fact that they are better absorbed in the stomach, most weak acids will be absorbed in the intestines because they have a longer transit time and surface area
65
Where will the charged form of a drug be trapped when working with a weak base?
It will be trapped on the more acidic side
66
What is the first pass effect?
Drugs that are absorbed in the GI tract go to the liver via portal system before entering circulation. The liver will metabolize a large fraction of the drug
67
What are the three most important aspects of drug absorption?
1. Lag time (formulation, route, gastric emptying)
2. Extent of absorption (bioavailability)
3. Rate of absorption
68
What determines the rate of absorption?
1. Product formulation
2. Drug interactions
3. GI physio, path
69
What five factors affect distribution?
1. Active transport into tissues
2. Chemical properties (lipid soluble, size, ions)
3. Binding to plasma proteins
4. Uptake into sinks (fat, bone, etc)
5. Tissue perfusion
70
What are the three major types of metabolism?
1. Microsomal (ER) cytocrome p450 oxidase
2. Glucuronide synthesis
3. Non-microsomal enzymes
71
Where will MOST of weak acids be absorbed?
despite the fact that they are better absorbed in the stomach, most weak acids will be absorbed in the intestines because they have a longer transit time and surface area
72
Where will the charged form of a drug be trapped when working with a weak base?
It will be trapped on the more acidic side
73
What is the first pass effect?
Drugs that are absorbed in the GI tract go to the liver via portal system before entering circulation. The liver will metabolize a large fraction of the drug
74
What are the three most important aspects of drug absorption?
1. Lag time (formulation, route, gastric emptying)
2. Extent of absorption (bioavailability)
3. Rate of absorption
75
Most P450 reactions make drugs ___________ which makes them more susceptible for ______________.
less hydrophobic making them more susceptible for renal filtration
76
What is autoinduction?
When a drug catalyzes its own metabolism
77
What are the most common drug interactions?
Inhibition or induction of drug metabolizing enzymes
78
Where does glucuronide metabolism take place?
ER- also broad spectrum and inducible like p450
79
What does glucuronide metabolism accomplish?
It makes the product more hydrophilic so it can be renally excreted
80
What makes non-microsomal metabolism different from glucuronide and p450 metabolism?
It cannot be induced, but it can be competitively inhibited
81
What 5 factors alter drug metabolism?
1. blood flow to the liver
2. age, sex
3. disease
4. drug interactions
5. genetics
82
Where are most drugs excreted?
| What are other options?
Kidneys
Lungs, skin, mammary glands
83
What are the four factors to consider for how well a substance will be filtered?
1. glomerular integrity
2. number of nephrons
3. size and charge of the molecule
4. protein binding
84
Molecules under MW ______ can be filtered and under ______ can be filtered well.
10,000 filtered, 1000 filtered well
85
The renal tubule can both actively_____ and actively ___ a variety of substates
secrete and reabsorb
86
What part of the kidney actively secretes organic acids and bases into the tubular lumen?
pars recta (straight part of proximal)
87
The distal nephron is responsible for elimination of what drug? What can compete with this elimination?
Digoxin
Competed by: spironolactone, quinidine and verapamil
88
Where does passive reabsorption of weak acids and bases occur?
collecting duct
89
What are the two major determinants for passive transport?
1. urine pH
| 2. flow rate
90
Weak acids are more reasborbed in ______ urine and weak bases are more reabsorbed in _____ urine.
acids in acidic pH
| bases in basic pH
91
What are two examples of weak acids that would be reabsorbed in acidic urine?
barbiturates and salicylates
92
What is an example of a weak base that would be reabsorbed in basic urine?
amphetamines
93
Increased renal flow rate ________ excretion.
| What are the two factors that make this true?
promotes or increases
1. increased flow = dilute urine= less conc gradient
2. less time for diffusion
94
Because of varying distribution times, when should you take a patients blood to get accurate levels?
just before the next dose
95
Most P450 reactions make drugs ___________ which makes them more susceptible for ______________.
less hydrophobic making them more susceptible for renal filtration
96
What is autoinduction?
When a drug catalyzes its own metabolism
97
What are the most common drug interactions?
Inhibition or induction of drug metabolizing enzymes
98
Where does glucuronide metabolism take place?
ER- also broad spectrum and inducible like p450
99
What does glucuronide metabolism accomplish?
It makes the product more hydrophilic so it can be renally excreted
100
What makes non-microsomal metabolism different from glucuronide and p450 metabolism?
It cannot be induced, but it can be competitively inhibited
101
What 5 factors alter drug metabolism?
1. blood flow to the liver
2. age, sex
3. disease
4. drug interactions
5. genetics
102
Where are most drugs excreted?
| What are other options?
Kidneys
Lungs, skin, mammary glands
103
What are the four factors to consider for how well a substance will be filtered?
1. glomerular integrity
2. number of nephrons
3. size and charge of the molecule
4. protein binding
104
Molecules under MW ______ can be filtered and under ______ can be filtered well.
10,000 filtered, 1000 filtered well
105
The renal tubule can both actively_____ and actively ___ a variety of substates
secrete and reabsorb
106
What part of the kidney actively secretes organic acids and bases into the tubular lumen?
pars recta (straight part of proximal)
107
The distal nephron is responsible for elimination of what drug? What can compete with this elimination?
Digoxin
Competed by: spironolactone, quinidine and verapamil
108
Where does passive reabsorption of weak acids and bases occur?
collecting duct
109
What are the two major determinants for passive transport?
1. urine pH
| 2. flow rate
110
Weak acids are more reasborbed in ______ urine and weak bases are more reabsorbed in _____ urine.
acids in acidic pH
| bases in basic pH
111
What are two examples of weak acids that would be reabsorbed in acidic urine?
barbiturates and salicylates
112
What is an example of a weak base that would be reabsorbed in basic urine?
amphetamines
113
Increased renal flow rate ________ excretion.
| What are the two factors that make this true?
promotes or increases
1. increased flow = dilute urine= less conc gradient
2. less time for diffusion
114
Because of varying distribution times, when should you take a patients blood to get accurate levels?
just before the next dose
115
Most P450 reactions make drugs ___________ which makes them more susceptible for ______________.
less hydrophobic making them more susceptible for renal filtration
116
What is autoinduction?
When a drug catalyzes its own metabolism
117
What are the most common drug interactions?
Inhibition or induction of drug metabolizing enzymes
118
Where does glucuronide metabolism take place?
ER- also broad spectrum and inducible like p450
119
What does glucuronide metabolism accomplish?
It makes the product more hydrophilic so it can be renally excreted
120
What makes non-microsomal metabolism different from glucuronide and p450 metabolism?
It cannot be induced, but it can be competitively inhibited
121
What 5 factors alter drug metabolism?
1. blood flow to the liver
2. age, sex
3. disease
4. drug interactions
5. genetics
122
Where are most drugs excreted?
| What are other options?
Kidneys
Lungs, skin, mammary glands
123
What are the four factors to consider for how well a substance will be filtered?
1. glomerular integrity
2. number of nephrons
3. size and charge of the molecule
4. protein binding
124
Molecules under MW ______ can be filtered and under ______ can be filtered well.
10,000 filtered, 1000 filtered well
125
The renal tubule can both actively_____ and actively ___ a variety of substates
secrete and reabsorb
126
What part of the kidney actively secretes organic acids and bases into the tubular lumen?
pars recta (straight part of proximal)
127
The distal nephron is responsible for elimination of what drug? What can compete with this elimination?
Digoxin
Competed by: spironolactone, quinidine and verapamil
128
Where does passive reabsorption of weak acids and bases occur?
collecting duct
129
What are the two major determinants for passive transport?
1. urine pH
| 2. flow rate
130
Weak acids are more reasborbed in ______ urine and weak bases are more reabsorbed in _____ urine.
acids in acidic pH
| bases in basic pH
131
Increased renal flow rate ________ excretion.
| What are the two factors that make this true?
promotes or increases
1. increased flow = dilute urine= less conc gradient
2. less time for diffusion
