Kinetics Flashcards
1
Q
This route of drug administration is used to inject drugs directly into the CSF
A
Intrathecal
2
Q
A parenteral route with a slower onset than IV. Vasoconstrictors may be administered here to reduce the area of action of another drug
A
Subcutaneous
3
Q
What is the definition of absorption?
A
It is the site of administration to the bloodstream
4
Q
When dealing with absorption, the rate & efficiency is dependent on
A
The route, which is COMPLETE for IV drugs
5
Q
When drugs are too big or when they are charged, they often need this in order to move
A
An active transport (carrier protein)
6
Q
What is ionization?
A
The process of gaining a positive or a negative charge
7
Q
An Acid tends to _____ a proton
A Base tends to ______a proton
A
Acid- donates/releases
Base- accepts/absorbs
8
Q
Ionization is dependent on
A
the pH of the solution & the pKa of a drug
9
Q
What do we know when the pH and the pKa are the same?
A
Half of the drug is ionized
10
Q
What type of drug CANNOT move freely?
A
Ionized
11
Q
What type of drug can move through the membranes?
A
Non-ionized
Uncharged
Lipid Soluble
Free
Unbound
Active
12
Q
What is the ACID equation?
A
HA<–> H+ + A-
13
Q
Of the ACID equation, which side is NOT charged?
A
HA side
14
Q
Most drugs are
A
Weak acids/bases, which partially dissociates
15
Q
What is the BASE equation?
A
B + H+ <–> BH+
16
Q
What is another name for pKa?
A
Dissociation constant
17
Q
The pKa measures
A
The strength of interaction of compounds with a proton
18
Q
The lower the pKa, the
A
Stronger the acid
19
Q
When computing the acid/base problems, what are you comparing?
A
The pH to the pKa
20
Q
When the pH is below the pKa,
A
More drug will be in the ionized form
21
Q
When the pH is above the pKa,
A
There will be less ionization
More NON-ionization
22
Q
Are Ionized drugs charged or uncharged?
A
Charged
23
Q
Ionized drugs are (active/inactive)
Ionized drugs are (lipophilic/hydrophilic)
A
INACTIVE
HYDROPHILIC
24
Q
Ionized drugs are cleared how?
A
They are excreted by the kidneys
25
Which form is more polar? Unionized or Ionized form?
Ionized
26
The unionized form of a drug is _______ & _______
Active & Lipophilic
27
Unionized drugs go though
Hepatic metabolism
28
What happens when you place an ACID into a BASIC solution?
Proton donation
ACIDIC DRUG becomes highly ionized
Cleared & not active
29
What happens when you place a BASE into an ACIDIC solution?
Proton acceptance
BASIC DRUG becomes ionized
Cleared & not active
30
What happens when you add an acid to an acidic solution?
Drug keeps their protons & is unionized
31
What happens when you add a base to a basic solution?
Drug keeps protons & is unionized
32
What factors affect absorption?
Blood Flow
Drug Solubility
Route
Surface Area
33
Increased resistance means
Decreased flow
34
Which absorption route is the slowest? The fastest?
Slow-GUT
Fast-LUNGS
35
When is bioavailability 1 (100%)?
When a drug is given IV
36
What is bioavailability?
A drug fraction that reaches systemic circulation, chemically unchanged
37
What influences bioavailability?
Chemical stability & formulation of the drug
Drug solubility
First pass metabolism
Route
38
What is distribution?
When a drug leaves the site of where it was administered & enters the plasma/cell/tissues
Drug moves from an area of high concentration & disperses throughout the body system in an even more dilute form
39
What factors influence distribution?
Blood flow
Capillary permeability
Chemical structure
Protein binding
40
What is the most active/common protein for binding?
Albumin
41
What happens once a drug becomes bound?
It is now trapped, becoming inactive
42
What can a drug do when it is not bound and is freely moveable?
Can enter tissues (distribute) & is considered pharmacologically active, causing more effect in the body
43
What has the strongest affinity?
Anionic drugs (weak acids) & Hydrophobic
44
What has the weakest affinity?
Basic & neutral drugs (Hydrophilic)
45
What decreases albumin capacity?
Liver damage
Elderly
Kidney damage
Malnourished
Pregnancy
46
A 70kg person has how much TBW?
42L
47
Of the 42L of total body water, how mush is intracellular & extracellular?
Intracellular- 28L
Extracellular- 14 L
10L interstitial; 4L plasma
48
Central compartments include...
Lungs
Endocrine Glands
Brain
Heart
Kidneys
Liver
49
Peripheral compartments include
Skin
Fat
Muscle
50
What is the equation for Volume of Distribution?
Vd=Amount of drug/Desired plasma concentration
51
Vd tell us...
How well/quickly a drug will quickly distribute, free & unbound in the plasma & interstitial fluid
52
The greater the Vd,
The larger the volume
53
When the Vd is low,
It means the drug does not move well
54
When the Vd exceeds total body water, it means the drug is...
Lipophilic
Non-ionized
55
What dose will be required when Vd exceeds total body water/
A higher dose will be required to reach Cp (plasma concentration)
56
When the Vd is LESS than total body water, the drug is considered
HYDROPHILIC (water loving) and a LOWER dose is required
57
Vd is influenced by
Characteristics of the drug & patient
Elimination
Distribution
58
Increasing the Vd will...
Reduce the drug in the plasma & increase half-life
59
A larger Vd is harder to get rid of because
You need to rid the body of the drug in the plasma
60
When free drug is available & highly protein bound, how does this affect Vd?
Vd will be increased
61
Vd can help us determine
How much drug we need to reach a specific plasma concentration (Cp)
62
Will your loading dose increase or decrease with a large Vd?
Increase
63
What is the equation for loading dose?
Loading dose= Vd x Desired Cp/ Bioavailability
64
What is the goal of metabolism?
The main goal is to take an active drug and turn it into its inactive form for excretion
65
What happens to a drug after it is metabolized
It is no longer in its active, lipid soluble state. It is now inactive & water soluble
66
What are the 2 exceptions for metabolism?
An Active metabolite
A prodrug
67
What is a prodrug?
It is when a drug is given, but only becomes active once it is metabolized into its active form, meaning the original drug was inactive
68
What is an active metabolite?
The original drug and the active metabolite will have similar therapeutic effects
69
What are common sites for metabolism?
Liver
Plasma
Kidneys
Lungs
GIT
70
What are the 3 phases of metabolism?
Modification
Conjugation
Elimination
71
What happens in the modification stage?
The drugs water solubility is increased and may be excreted or prepped for Phase II
72
Conjugation involves...
Increasing the drugs water solubility
73
Elimination in the metabolism stage includes
Drug transportation across membranes by an ATP-dependent carrier protein
Kidney, Liver, GIT
74
What happens in the Phase I metabolism pathway?
Oxidation
Reduction
Hydrolysis
75
Oxidation is ____ of an electron
Reduction is ___ of an electron
Oxidation-Removal
Reduction- Add
76
Hydrolysis is...
Adding water to split a drug apart, involving plasma or tissue esterases
77
What occurs in the Phase II metabolism pathway?
Conjugation, where there is addition of a polar & water soluble substrate (covalent bond)
78
Microsomal enzymes are responsible for
Biotransformation in the liver
79
Microsomes are
Endoplasmic reticulum fragments from tissue breakdown
80
Cytochrome is an
Iron-containing heme bound to a protein
81
What is the primary system for the liver to metabolize sybstances
Microsomal enzymes
CYP=450
82
Enzyme Inducers...
Increase Clearance
Faster breakdown
Decrease drug plasma level
May need dose increased
83
Enzyme Inhibitors...
Decrease Clearance
Slower breakdown
Increase drug plasma levels
May need dose decrease
84
Kinetics of Metabolism is effected by
Blood flow
Amount of drug given
Concentration of the drug
Efficiency of metabolizing system
Organ capacity
85
Which kinetic metabolism method involves a constant AMOUNT of drug metabolized per time, has MORE DRUG than enzymes, & is SATURATED?
Zero-Order
86
Which kinetic metabolism method involves a constant FRACTION metabolized per time, MORE ENZYME than drug, blood flow dependent, & has NO saturation?
First order
87
What are 3 types of plasma metabolism?
Hydrolysis (common)
Plasma enzymatic reactions
Hoffman elimination
88
Plasma enzymatic reactions involve...
No enzymatic induction, meaning that it will not be influenced by other drugs that will increase enzymes
89
Hoffman elimination is the
Spontaneous chemical elimination reaction, which depends on pH & body temperature
It is important to keep the patient away from acidosis & hypothermia
90
Elimination is drug removal from the_____
Excretion is drug removed from the _______
Plasma; Body
91
Clearance is
The volume of plasma that is completely cleared of a drug per unit of time
92
Clearance is dependent upon
Efficiency of the drug being delivered (blood flow) & drug removal (extraction)
93
Clearance is directly related to
Organ blood flow
Extraction Ratio
Drug dose
94
Explain extraction ratio
Efficiency of an organ removing a drug from the plasma, entering the organ, & it being broken down
95
Clearance is indirectly related to
Drug half-life
Drug concentration in the central compartment
96
The greater you clear a drug,
The shorter the half-life
97
The greater the clearance, the
Lower the concentration
98
What is the extraction ratio equation?
Extraction ratio=arterial concentration-venous concentration/arterial concentration
99
When the extraction ratio is >70%, metabolism & clearance are
Flow-limited (flow dependent)
100
High extraction ratio is dependent on
Free (unbound) drug
101
High extraction ratio is proportional to
Change in hepatic blood flow
102
Low extraction ratio <30% is independent of
Liver blood flow
103
In low extraction ratio, metabolism & clearance are
Capacity limited (capacity dependent)
104
Changes in protein binding affect clearance in
Low capacity ratio states
105
Volume of plasma cleared of a drug is determined by...
A drugs polarity
pH of glomerular filtrate
Hydrophilic-excreted unchanged (water soluble)
Lipophilic- biotransformed (water soluble)
106
Polar drugs will
NOT be reabsorbed
107
When and where will unionized (lipid soluble) drugs (may) be reabsorbed?
In the distal tubule depending on urine pH & flow rate
108
When a patient has acidic urine, there is reabsorption of____ & excretion of________
Reabsorb acidic drugs
Excrete basic drugs
109
When a patient has alkaline (basic) urine, there is reabsorption of _______ & excretion of _______
Reabsorb basic
Excrete acidic
110
When should you adjust your dose of medication?
When >50% of the drug is renally cleared
When renal function is decreased 50% of normal
111
Definition of half life
It is the time required to remove 50% of a drug from the BODY following a rapid IV injection
112
What is directly related to half life?
Indirectly related?
Direct- Vd
Indirectly- Clearance
113
Approximately, how many half lives does it take to eliminate ~97% of a drug?
5
114
The more a drug distributed, the longer the
Half life
115
Half life equation
Half life= Vd/ Rate of Clearance
116
Half life is Increased by...
Decreased RBF, extraction ratio & metabolism
Displacement of drug from albumin (free)
117
Cp (plasma concentration) is influenced by...
Distribution
Redistribution
Excretion
Metabolism
118
One compartment model is based on
Input of drug dosage/interval/rate
Output of constant elimination
119
Multi- compartment model is based on
Concentration gradient from central compartment (plasma) to peripheral (tissues)
120
Multi- compartment phases include
Rapid
Slow
Terminal
121
Lipophilic drugs will have a larger Vd, causing this on a chart
A steeper slope, equalling a rapid reduction in Cp
122
On the graph (slide 65), the flattened slope of B is representing
Redistribution & elimination
123
Redistribution involves
A drug leaving the tissues & re-entering the plasma
124
In the 3 compartment model, drug movement is dependent on
Vd
Plasma & tissue concentrations
Rate constants (k)
Half-lives
Clearance
125
What is the rate constants (k)?
The speed at which a drug molecule moves between compartments or is eliminated
126
Define steady state
It is measuring how much of a drug coming in equals how much is coming out
127
In steady state, what must equal?
Infusion rate/dosing interval must equal clearance
128
How many half lives does it take to reach steady state?
4-5
129
What is half time?
The time it takes for 50% of a drug to be removed from the plasma during elimination
130
Half time measures a
Constant fraction of drug being eliminated & is only applicable in a 1 compartment model
131
What is context sensitive half time?
It is the time required for Cp (plasma concentration) to decline by 50%, following a steady state IV infusion
132
What is the "context" in CSHT?
The duration
133
What is context-sensitive EFFECT site elimination?
Tells us how long it takes to get the drug out of the effect site
