U3.1 PHARMACOKINETICS Flashcards
(125 cards)
1
Q
What the body can do to the drug
A
Pharmacokinetics
2
Q
Dose-concentration relationship
A
Pharmacokinetics
3
Q
Effects of the biologic system on drugs
A
Pharmacokinetics
4
Q
T/F Pharmacodynamics deals with the processes of absorption, distribution, [metabolism], and elimination [or excretion] of drugs
A
F
5
Q
Concentration of a drug at the receptor site [in contrast to drug concentrations that are more rapidly measured, eg, blood]
A
Effective Drug Concentration
6
Q
The amount of drug waiting to associate with its receptor
A
Effective Drug Concentration
7
Q
T/F Not all of the drug that the patient takes in would take effect
A
T
8
Q
3 contributors to plasma concentration
A
- Rate of input of the drug by absorption
- Rate of distribution to peripheral tissue
- Rate of elimination, or loss, from the body
9
Q
2 basic parameters of pharmacokinetics
A
- Volume Distribution (Vd)
- Clearance (CL)
10
Q
measure of the apparent space in the body available to contain the drug
A
Volume distribution
11
Q
measure of the apparent space in the body available to contain the drug
A
Volume distribution
12
Q
measure of the ability of the body to eliminate the drug
A
Clearance
13
Q
related the amount of drug in the body to the concentration of drug (C) in blood of plasma
A
Volume distribution
14
Q
T/F Initial distribution is in the liver, kidney and brain
A
T
15
Q
T/F Distribution is faster in muscle, viscera, fat and skin
A
F
16
Q
T/F Distribution happens in the interstitial and intracellular fluids
A
T
17
Q
Amount of drug in the body to the plasma/serum concentration
A
Volume Distribution
18
Q
distribute your
drug inside the tissues
A
Intracellular
19
Q
distribute drug outside the cells
A
Extracellular
20
Q
T/F When a drug is avidly bound in peripheral tissues, its concentration in plasma may drop to very low values even if the total amount in the body is large
A
T
21
Q
↑ Vd = distributed in ___
A
peripheral tissue
22
Q
Relationship of Vd to plasma volume
When a drug is completely retained in the plasma compartment
A
Volume of distribution (Vd) = plasma volume
23
Q
Rate of elimination compared to drug concentration (C)
A
Clearance (CL)
24
Q
Depends on the drug and the organs of elimination in the patient
A
Clearance (CL)
25
2 major sites of drug elimination
Liver & Kidney
26
↑ Vd = ___ plasma concentration
↓ plasma concentration
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↑ Vd = distributed to ____ e.g. urine, brain
tissues
28
↓ Vd = stays in the _____ e.g. septicemia
blood
29
T/F In clearance, drugs are eliminated with first-order kinetics
T
30
T/F Clearance is constant and can be calculated via area under the curve (AUC)
T
31
First Order = ___ drug concentration, ___ elimination
↑ drug concentration, ↑ elimination
32
T/F CL = rate of elimination / plasma concentration
T
33
T/F Continuous elimination half-life makes the initial concentration smaller & smaller; thus slowing down elimination.
T
34
Clearance : 2 Types of Elimination
1. Capacity-Limited Elimination
2. Flow-Dependent Elimination
35
T/F During capacity-limited elimination, clearance does not remain constant but will vary depending on the concentration of drug that is achieved
T
36
T/F Most drug elimination pathways by metabolism will not become saturated if the dose and therefore the concentration are high
enough.
F; it will become saturated
37
Type of elimination
Some drugs are cleared very readily by the organ of elimination
Flow-Dependent Elimination
38
Type of elimination
When blood flow to an organ does not limit elimination, the relation between elimination rate and concentration (C) is expressed mathematically in equation
Capacity-Limited Elimination
39
Type of elimination
Most of the drug in the blood perfusing the organ is eliminated on the first pass of the drug through the organ.
Flow-Dependen elimination
40
T/F For Flow-Dependent elimination, the elimination of these drugs will thus depend primarily on the rate of drug delivery to the organ of elimination.
T
41
Flow Dependent Elimination
main determinant of drug delivery
Blood flow to the organ
42
Flow Dependent Elimination
important for extensively bound drugs that are highly extracted
plasma protein binding and blood cell partitioning
43
Time it takes for the amount of concentration of a drug to fall to 50% of an earlier measurement
Half-Life T1/2
44
T/F Drugs eliminated by first-order kinetics are constant
T
45
Determines the rate at which blood concentration rises during a constant infusion and falls after administration is stopped.
Half-Life T1/2
46
T/F Drug accumulation happens when repeated drug doses will be accumulated until dosing stops
T
47
inversely proportional to the fraction of
dose lost in each dosing interval
Accumulation
48
drug administration = elimination
Steady State Concentration
49
Dose in = Dose Out
Steady State Concentration
50
# of Half lives for the drug to have a steady state
4
51
Fraction of the administered dose of the drug that reaches the systemic circulation
Bioavailability
52
Equal to the amount absorbed over the amount administered
Bioavailability
53
Bioavailability
Unity or 100%
Intravenous administration
54
Bioavailability
< 100%
First-pass elimination by the liver.
Oral administration
55
T/F Drugs are more absorbed in the small intestines because it has a larger surface area.
T
56
Liver immediately metabolizes and makes it water soluble to make it easier to be excreted via kidneys.
First pass metabolism
57
Routes with low bioavailability
Sublingual, Rectal, Inhalation or nasal, Transdermal patches
58
T/F Bioavailability is dependent on extent of absorption, first-pass effect, rate of elimination and site of administration.
F; extent of absorption, first-pass effect, rate of absoprtion and site of administration
59
Bioavailability route
100% BA; most rapid onset
Intravenous (IV)
60
Bioavailability route
75 to < 100; Large volumes often feasible, may be painful
Intramuscular (IM)
61
Bioavailability route
75 to < 100; Smaller volumes than IM, may be painful
Subcutaneous (SC)
62
Bioavailability route
5 to <100; Most convenient; 1st-pass effect may be important
Oral (PO)
63
Bioavailability route
30 to <100; Less first-pass effect than oral
Rectal (PR)
64
Bioavailability route
5 to <100; Often very rapid onset
Inhalation
65
Bioavailability route
80 to ≤100; Usually very slow absorption, lack of first-pass effect
Transdermal
66
Bioavailability route
Prolonged duration of action
Transdermal
67
Determined by the site of administration & drug formulation
Rate of Absorption
68
Type of drug absorption
Rate is independent of the
amount of drug remaining in the gut.
Zero-order drug absorption
69
Type of drug absorption
When the rate of absorption is proportional to the concentration.
First-order drug absorption
70
T/F Systemic clearance is not affected by bioavailability
T
71
T/F During Oral administration, concentration of drug
metabolites will be increased compared to IV
administration
T
72
Alternative Routes
direct access to systemic but not portal veins
Sublingual Absorption & Transdermal Route
73
Alternative Route
drain into inferior vena cava, bypassing the liver
Lower rectum suppositories
74
Alternative Route
bypass first-pass effect by inhalation to lungs
Non-gastrointestinal (“parental”) routes
75
Time Course of Drug Effects
Instantaneous effect
Immediate Effect
76
Time Course of Drug Effects
Directly related to concentration
Immediate Effect
77
Time Course of Drug Effects
Due to distributional delay
Delayed Effect
78
Time Course of Drug Effects
Delayed expression of the physiologic substance needed for the effect.
Delayed Effect
79
Time Course of Drug Effects
slow turnover of a physiologic substance that is involved in the expression of the drug effect
Delayed Effect
80
Time Course of Drug Effects
Constant infusion
Cumulative Effects
81
Time Course of Drug Effects
Aminoglycosides cause renal toxicity if given constantly.
Cumulative Effects
82
Time Course of Drug Effects
Intermittent dosing only.
Cumulative Effects
83
Fraction of the drug removed from the perfusing blood during passage to the organ
Extraction ratio
84
Measure of the elimination of the drug by that organ.
Extraction
85
↑ hepatic extraction, __ first-pass effect
↑ first-pass effect
86
Drugs are eliminated unchanged or as metabolites
Excretion
87
Polar compounds are more efficiently eliminated
Excretion
88
The concentration wherein you see the desired
therapeutic effects of the drug
Target Concentration
89
T/F Target concentration will also depend on the specific
therapeutic objective
T
90
Plan for drug administration over a period
Dosage Regimens
91
Achievement of therapeutic levels of the drug in the body without exceeding the minimum toxic concentration
Dosage Regimens
92
Dose needed to maintain a steady state of concentration
Maintenance Dose
93
Maintain plasma concentration within a specified range
over long periods of therapy
Maintenance Dose
94
Most important parameter in defining rational drug dosage
Clearance
95
For drugs with long half-lives and longer time to reach a steady state
Loading Dose
96
Given to promptly raise the concentration of the drug to the target concentration
Loading Dose
97
Important factor to consider in loading dose
Volume of distribution
98
↑ volume of distribution, __ loading dose
↑ loading dose
99
4 Pharmacokinetic Variables
1. absorption
2. clearance
3. volume of distribution
4. half life
100
Pharmacokinetic Variable
Compliance of patient is important.
Absorption
101
Pharmacokinetic Variables
Variations in bioavailability are usually due to variations in metabolism
Absorption
102
Pharmacokinetic Variables
Most important parameter in designing dosage regimen.
Clearance
103
Pharmacokinetic Variables
may be anticipated when there is major impairment of the function of the kidney, liver, or heart
Abnormal clearance
104
Pharmacokinetic Variables
Good indicator of renal function
Creatinine Clearance
105
Pharmacokinetic Variables
↑ Vd = ____
↓ Vd = ____
↑ Vd = tissues, body waters, extracellular accumulation of body fluids
↓ Vd = plasma
106
Pharmacokinetic Variables
Dependent on clearance and volume of distribution
Half-life
107
2 Pharmacodynamic Variables
1. Maximum Effect
2. Sensitivity
108
Pharmacodynamic Variables
No more increase in effect even if the concentration is
increasing
Maximum effect
109
Pharmacodynamic Variables
Increased, exaggerated response to small doses
Sensitivity
110
Pharmacodynamic Variables
EC50, the concentration required to produce 50%
of maximum effect
Sensitivity
111
More highly protein bound drug will displace the less protein bound drug
Plasma binding proteins
112
Acidic drugs bind to ____
albumin
113
Basic drugs bind to ____
α1-Acid glycoprotein
114
Average total amount of drug in the body does not change over multiple dosing intervals
Steady State Concentration
115
Safe opeing between the MEC and MTC of the drug
Therapeutic Window
116
used to determine the range of plasma levels that is acceptable when designing a dosing regimen
Therapeutic Window
117
Peak and Through Concentrations
determines the desired trough levels of a drug given intermittently
MEC : Minimum effective concentration
118
Peak and Through Concentrations
determines the permissible peak plasma concentrations
MTC : minimum toxic concentration
119
Most appropriate time to measure drug concentration
2 hours
120
T/F With maintenance dose drugs, you've already reached the steady state concentration
T
121
First Order kinetics
↑ drug concentration, ____ rate of elimination
↑ rate of elimination
122
↑ Vd = distributed to tissues, ____ half-life
↑ longer half-life
123
↓ Vd = stays in the blood, ____ half-life
↓ shorter half-life
124
↑ drug accumulation, ____fraction of the dose lost in each interval
↓ fraction of the dose lost in each interval
125
↓ affinity drugs = ____ plasma concentration
↑ plasma concentration
