Pharmacokinetics Flashcards
1
Q
Pharmacokinetics involves
A
- Absorption
- Distribution
- Elimination (excretion, metabolism)
- Steady-state concepts
2
Q
Define Pharmacology
A
Study of drugs; interaction between the body/drug
3
Q
Pharmacological effects of Drug concentrations
A
- Therapeutic (positive)
- Toxic (Negative)
4
Q
Pharmacodynamics relationship with body/drug
A
Is what the drug does to the body
5
Q
Pharmacokinetics relationship with body/drug
A
Is what the body does to the drug
6
Q
Pharmacokinetics is
A
The relationship between dosage regimen and drug concentrations
7
Q
Pharmacodynamics is
A
The relationship between drug concentrations and their pharmacological effects
8
Q
Pharmacokinetic relationship with a Drug A, vs adding another drug
A
9
Q
Pharmacodynamic relationship of drug concentration and pharmacological effects
A
Middle square is Toxicity
10
Q
How pharmacodynamics and pharmacokinetics are related
A
11
Q
Pharmacokinetic interaction: Changes in outcome are the result of changes in the relationship between the _______ and the _____________
A
- DOSE
- Concentration
12
Q
Pharmacokinetic interaction: The pharmacologic effect has changed as a result in a change in the _________________________.
A
Change in drug concentration
13
Q
Pharmacodynamic interaction: Changes in outcome are the result of changes in the relationship between the _______________ and the _________.
A
- Drug concentration
- Effect
14
Q
Pharmacodynamic interaction: The pharmacologic effect has changed despite a lack of change in the __________________________.
A
Drug concentration
15
Q
Functions of Cell membrane
A
- Barrier to drugs
- Divides the body into compartments
- More lipid-soluble substances move more freely across membranes
- less lipid soluble substances pass less freely across membranes
16
Q
Examples of less lipid-soluble substances (cell membrane)
A
- polar substances
- relatively lipid-insoluble
- ionized substances
17
Q
What is absorption bioavailibily
A
- Measure of the amount of drug that is BIO AVAILABLE
(i. e. available to exert a systemic effect on the body) - Measure of systemic drug exposure
(i. e. how much a drug is absorbed)
18
Q
What is Absolute bioavailability
A
How much drug is absorbed
19
Q
Relative and absolute bioavailabilty combined
A
How two dose forms compare in terms of systemic drug exposure
20
Q
What kinetic parameter quantifies drug exposure?
A
- The AUC produced by the serum concentration-vs-time profile
- Expressed % of product which reaches the systemic circulation
21
Q
How does this chart explain bioavailability?
A
-Bigger the area under the curve the more bioavailability (drug in systemic circulation)
22
Q
Bioavailability depends on the:
A
- absorption characteristics of the drug and dose form
- metabolism occuring prior to the drug reaching the systemic circulation
(i. e. first pass effect) - presence of interacting substances
(i. e. drugs, food/no food/type of food)
23
Q
Why you calculate absolute bioavailability
A
- Know how much drug is absorbed/reaches systemic circulation
- How the two dose forms compare in terms of systemic drug exposure
24
Q
Purpose of relative bioavailability
A
To calculate/approximate the bioavailability relating to drugs
i.e. Tablet relative to solution
or
Solution relative to tablet
25
Comparison of bioavailability and relative bioavailability
All measure of bioavailability could be called measures of relative bioavailability.
-Compare AUC of 1 product RELATIVE to another
26
If bioavailability comparison is to a product with absolute (100%) absorption what type of bioavailability is it?
ABSOLUTE
27
If bioavailability comparison is to a product with less than absolute (100%) absorption what type of bioavailability is it?
RELATIVE
28
Based on this chart, which drug would you choose? PO or IV
Because the AUC is similar, the pharmacist could choose PO or IV
29
What is the effect of different conditions on drug bioavailability
The approximate bioavailability of a drug administered on an empty stomach RELATIVE to its administration with food:
30
What does it mean if value is over 100
That fasting is more bioavailable
31
What does it mean if value is under 100
More bioavailable with food
32
What is volume of distribution
To account for observed initial drug concentrations following drug administration, researchers calculate an "apparent" volume
-It is NOT a true physiologic volume
33
In terms of compartments, what is the central pool aka the blood stream
The central compartment
34
In terms of compartments, what is the pools with different cells
The peripheral compartments
35
Which compartment do you take measurements from?
The central compartment
36
Volume of distribution is increased with
- Drugs that have a higher lipid solubility
- Drugs that have lower protein binding
- Drugs that have greater tissue binding
37
Why do drugs that have higher lipid solubility have increased volume of distribution?
They can go further than lipid insoluble because they can cross cell membrane
38
Why do drugs that have lower protein binding have a increased volume of distribution?
More free molecules and can move out of the central compartment
39
Why do drugs that have greater tissue binding have an increased volume of distribution?
They leave the central compartment and have increased tissue affinity, they are unlikely to come back to the blood stream readily
40
How do we use Volume of Distribution
- Determining drug doses
- Provide clinicians with a sense of the spaces/areas/compartments into which the drug distributes
(i. e. extent of drug distribution/where it is going to be in body)
41
Formulas for determining doses?
42
Describe Distribution Spaces
- Volume of Distribution measured in L/Kg (body weight) or L
- Drugs can be roughly categorized according to their volume of distribution
i. e. _\<_ .25 L/kg has a small VD (spends less time in central compartment, and therefore is affected by hydration levels)
\>.70 L/Kg (spends most time in peripheral compartment, these drugs are well dialyzed)
43
Small Vd concentrates where?
-Concentrates in ECF (central compartment)
44
Mid range VD is found in what compartment
- Black: within cells/tissue bound (peripheral compartment)
- White: Extracellular fluid (central compartment)
45
Large VD concentrates in what compartment
-Concentrates in cells/tissues (peripheral compartment)
46
Describe volume of Distribution, Pool analogy
Same amount of a two different drugs, with completely different distributions
47
Describe volume of Distribution, Patient analogy
Drugs react differently with every patients, take their size into consideration
48
Drug Elimination two forms
- Biotransformation
- Excretion
49
Drug Elimination Biotransformation is
Drug is chemically altered to form a metabolite that is more "excretable" than parent drug
50
Drug Elimination Excretion is
Removal of a drug or a metabolite from the body via the organ
51
What organ excretes drugs
kidneys
52
Which substances are more ready for renal excretion?
Lipid insoluble
(less time in periphery, more time in central compartment)
53
What organ is where biotransformation occurs?
Liver
54
Biotransformation Phase I reactions on drugs
- Introduce functional groups (OH, -COOH, -SH, -O-, or -NH2) to prepare for Phase II reactions
- these reactions often lead to drug inactivation
55
What is the most common phase I reaction in biotransformation
Oxidation
56
What is Oxidation
- most common Phase I reaction
- Mediated by cytochrome P450 enzymes
- Most sensitive to changes in liver function
(i. e. smoking, alcohol, aging)
- Reduction
- Hydrolysis
57
What is Phase II reactions in biotransformation
- drug or metabolite is conjugated to glucuronic acid, methyl group, acetyl group, sulfate group
- these reactions produce a metabolite which is less lipophilic (more polar)
- Enzymes are less susceptile to change in liver function
58
What is the half life of a drug?
of a drug is the measure of how long it takes for half of a drug to be eliminated from the bloodstream.
59
What is clearance?
The rate of elimination of substances from the blood
60
in Dose-serum concentration relationships:
For a drug whose elimination processes are NOT easily maximized (PK verbiage=NOT easily saturated), the elimination rate of that drug increases in _______________ to the serum drug concentration (referred to as \_\_\_\_\_\_\_\_\_\_\_\_\_\_). For such a drug, the serum drug concentrations produced are ______________ to the dose administered.
-Half life is independent of drug concentrations
- Direct proportion
- 1st order elimination
- directly proportional
61
In first order elimination what is this graph going to look like?
LINEAR
62
In 1st order elimination what does this graph look like?
Linear
63
The proportionality of serum concentration in 1st order elimination for IV and Oral
Holds true for IV drugs
May not hold true for oral drugs (absorption may decrease with different doses)
64
For oral administration what do these graphs show
Body can only absorb so much of the drug!
65
in Dose-serum concentration relationships:
For a drug whose elimination processes ARE easily maximized (PK verbiage= easily saturated), the elimination rate of that drug is \_\_\_\_\_\_\_\_. This is referred to as \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. For such a drug, the serum drug concentrations produced are ___________ to the dose administered. Small increases produce large increases serum drug concentrations
-Half life is DEPENDENT of drug concentrations
- Constant
- Zero order elimination
- Disproportional
- Large
66
Zero order elimination graph look like
Increases and then plateaus (non-linear)
67
Zero order elination graph looks like
increases non linearly
68
What is important to remember about zero order drugs
BE CAREFUL
These drugs are disproportional to the dose admninstered
Most drugs are NOT eliminated in this manner
69
How many Half lives to get to steady state
4-7 half lives
| (5 is common)
70
At steady state, what is the relationship between the rate of drug going into a patient and the rate of drug leaving the patient?
- the rate of drug going in = the rate of drug going out
- the amount of drug eliminated over the dosing interval = the dose administered
71
What is happening with regard to drug accumulation during steady-state?
Drug accumulation reaches an equilibrium (acccumulation isnt occuring any further)
72
Name factors that can cause a patients drug regimen to be "knocked out" of steady state?
Anything that changes the input or output
(then needs to go through half lives again to stabilize)
73
Primary determinant of how long it will take for a drug regimen to reach steady-state?
The time to reach steady-state is dependent on the drugs half life
