Week 2 Lectures Flashcards
1
Q
Metabolism is a ______ mechanism against adverse effects of ________ ________.
A
defense, lipophilic xenobiotics
2
Q
What would happen in biological systems without drug metabolism?
- ________ compounds would stay in the body for a much longer period of time.
- Drugs would have a _______ activity
- There would be a tissue drug _______
- Potential ______.
A
Absorbed, prolonged, accumulation, toxicity
3
Q
The _____ is the major organ for drug metabolism in the body
A
liver
4
Q
Drug metabolism in the liver depend on factors such as?
• _________ properties of the liver (existence of major drug metabolism ______)
• Hepatic _____/______ rate
• Drug ________ to and _______ by hepatic metabolic sites
• ________ properties of the drug (______, _______ ______, _______ _____)
A
Biological, enzymes, volume, perfusion, accessibility, extraction, Physicochemical, pKa, lipid solubility, molecular weight
5
Q
Most drugs are eliminated by ______ metabolism, ______ excretion, or ____.
A
hepatic, renal, both
6
Q
Lipid-soluble drugs require conversion to a _____-
soluble form before they can be eliminated by the _______
A
water, kidney
7
Q
Hepatic metabolism can be divided into phase I and
phase II. Explain this process.
A
The main goal of phase 1 and 2 is to increase water solubility
8
Q
The majority of drug metabolism occurs in ______ but the _____ is not the only site. Other organs with substantial metabolic capacity include?
A
liver, liver, kidney, lungs, skin, GI tract.
9
Q
The ______ is also capable of metabolizing some drugs, although this capacity is only occasionally of clinical importance
A
kidney
10
Q
Most metabolizing enzymes are located in the _______ ________ _______ (___) of the
hepatocyte, others are located in the ______ of the cell.
A
smooth endoplasmatic reticulum, SER, cytosol
11
Q
The enzymes located in the SER consist of a protein (________) with an ____ central core (______) that absorbs light at ___ nm when bound to _______ _______.
A
cytochrome, iron, pigmented, 450, carbon monoxide
Cytochrome 450 is the most important family of enzymes.
12
Q
The enzymes in the SER are actually an enzyme _______ that can be genetically classified as a ________ containing several ______ of enzymes.
A
system, superfamily, subfamilies
13
Q
All CYP-mediated drug metabolic reactions involve the addition of a _______ atom of _______ onto the substrate.
A
single, oxygen
14
Q
Examples of cytochrome P450 enzymes and
substrates in the dog. DO WE HAVE TO KNOW THIS?
A
did she say we have to know this chart? could not understand
15
Q
The major phase I drug-metabolizing reactions include?
A
Oxidation, hydrolysis, reduction.
16
Q
In Phase 1 metabolism, oxidation is the addition of _______ across a ______ double bond, addition of _______ to a carbon chain, and the loss of an ______.
A
oxygen, carbon, oxygen, electron
17
Q
In Phase 1 metabolism, hydrolysis is the ________ of the drug molecule and addition of a _____ molecule to each of the _____ portion.
A
splitting, water, split
18
Q
In Phase 1 metabolism, reduction is the addition of ______ and an _____.
A
hydrogen, electron
19
Q
Most ______ drugs can be deactivated to inactive
metabolites. In contrast, some drugs can also be
activated from an inactive form, ______ to an
active drug, or from an active form to an ______ _______.
A
parent, prodrug, active metabolite
By first phase of metabolism, not everyone will be destroyed or activated.
20
Q
There are considerable differences among the species in the _______ of the oxidative enzymes
A
activity
21
Q
List these species in order from highest to lowest in regards to oxidation: cattle, dogs, cats, horses
A
Oxidation is higher in horses > cattle > dogs > cats
22
Q
The duration of pentobarbital anesthesia in horses is _______ than in dogs.
A
shorter
23
Q
Phase II, also known as ______, occurs when a _______ _____-soluble molecule is chemically added to either the ______ drug or its phase ____ metabolite
A
conjugation, large, water, parent, I
24
Q
Glucuronidation is the ______ ______ phase II reaction. Glucuronide conjugates are eliminated in the _____ and ____.
A
most common, urine, bile
25
\_\_\_\_\_\_ and ______ are also phase II reactions.
Sulfation, acetylation
the most important reaction is the glucorindation
26
Which of the following statements regarding phase I and II metabolic reactions is true?
A. Phase II acts only on phase I metabolites
B. Phase I acts on parents drugs and/or phase I metabolites
C. Phase II acts on parent drugs and/or phase I metabolites
D. Phase II acts only on parents drugs.
C. Phase II acts on parent drugs and/or phase I metabolites
B can not be true because there are no metabolites? in this phase.
27
What are the enzymes involved in phase II metabolism?
glucuronosyltransferase, sulfotransferase, N-acetyltransferase and methyltransferase
28
Most of ____________ is eliminated by glucoronidation and sulfation.
acetaminophen
Many drugs can be metabolized via different types of reactions.
29
As in humans, ________ in drug-metabolizing enzymes has been reported in dogs but it is
not as well described.
polymorphism
30
Polymorphisms in CYP metabolic enzymes have been associated with ________ \_\_\_\_\_\_.
therapeutic failure
31
Polymorphisms in CYP metabolic enzyme results in?
* Extremely rapid metabolism of a drug
* Toxic effects caused by decreased metabolism
32
Cytochrome-mediated clearance of anesthetic agents is less in _________ compared with other (\_\_\_\_\_\_ \_\_\_\_\_) dogs. Documented drugs include?
Greyhounds, nonsight hound
Thiopental, thiamylal and methohexital
33
Clearance of ________ by Greyhounds is three time less than by Beagles
propofol
34
Cats have very low activity of \_\_\_\_\_\_\_, but activity of ______ and _____ approximates that of dogs
or humans.
CYP2C, CYP2D, CYP3A
35
Notice which isoforms are associated with isoforms and which ones have a very low association
36
CYP2D15
In a study of 242 Beagles receiving celecoxib, approximately \_\_\_% were considered efficient metabolizers and \_\_\_\_% poor metabolizers. The PM group showed a ______ and maximum ___ almost twofold higher.
50, 50, bioavailability, PDC
37
Deficiencies in phase II metabolism have long been recognized in \_\_\_\_. This is because they have extremely low concentrations of some _______ \_\_\_\_\_\_\_.
cats, glucoronyl tranferases
38
Many drugs excreted as glucuronide conjugates in species other than cats are characterized by a ________ clearance and ______ pharmacologic responses. ____ levels may accumulate much more quickly.
prolonged, exaggerated, Toxic
39
Deficiencies in phase I demethylation and hydroxylation as well as phase II glucuronidation lead to a much ________ elimination of ______ and _____ \_\_\_\_ and _______ in the cat compared with other species
slower, phenols, aromatic acids, amines
40
Aspirin half-life approximates ___ hours in cats
compared with __ hours in dogs. To prevent
toxicity in the cat, aspirin is dosed every ___ to \_\_\_
hours, compared with twice daily in dogs.
36 , 8, 48, 72
41
Because cats are deficient in \_\_\_\_\_\_\_\_\_\_, excessive acetaminophen is shunted more aggressively back into phase __ metabolism, which produces toxic ______ \_\_\_\_\_\_. More _______ are produced than can be handled causing
destruction of _____ (\_\_\_\_ and \_\_\_\_)
glucuronidation, I , oxygen radicals, metabolites, tissues, liver, RBCs
42
Not all drugs that are conjugated with ________ are predisposed to toxicity in the cat.
glucuronide
43
The cat is deficient only in certain families of ________ \_\_\_\_\_\_\_\_.
glucuronyl transferase
44
Cats can _______ and ______ endogenous substrates such as \_\_\_\_\_\_, ______ hormones as
well as other species.
conjugate, excrete, bilirrubin, steroid
45
The degree of _______ and potential ______ depend on the drug substrate: level of \_\_\_\_\_\_, wide _______ margin (If accumulation occurs).
deficiency, toxicity, conjugation, safety
46
Drugs may be sufficiently metabolized by an alternative pathway: ?
Sulfate-conjugating system.
47
\_\_\_\_\_\_\_\_\_ is not a common route of elimination for xenobiotics, but it is an enzyme system whose deficiency in the ______ (\_\_\_\_ and other ____ species) is clinically relevant.
Acetylation, canine, dog, canine
48
The antiarrhythmic procainamide is _________ in humans to an active metabolite. This ________ metabolite is more potent than the _____ drug. Because of this the canine dose for _______ is considerably ______ than that in humans in order to
achieve an equivalent pharmacologic response.
acetylated, acetylated, parent, procainamide, higher
49
Sulfonamides are detoxified by \_\_-\_\_\_\_\_\_ in humans. The dog lacks the ability to acetylate ______ \_\_\_\_\_\_, relying on alternative metabolic pathways to convert sulfonamides to ____ \_\_\_\_ forms (\_\_\_\_\_\_\_\_ conjugation and aromatic \_\_\_\_\_\_\_\_\_\_)
N-acetylation, aromatic amines, less active, glucuronide, hydroxylation
50
Factors that can affect hepatic drug metabolism include
* The amount and activity of drug- metabolizing enzymes
* Hepatic blood flow
* A flow-limited drug
* Species, age, nutritional status, tissue storage, health status
51
Some diets may inhibit or induce the _______ enzyme system. Flavonoids found in ______ \_\_\_\_\_
inhibit CYP3A4 in the _____ \_\_\_\_\_\_\_\_. Ginkgo biloba induces \_\_\_\_\_\_\_.
CYP450, grapefruit juice, small intestine, SYP219A
52
The level of oxidative enzymes is lower in ____ \_\_\_\_\_\_ animals. Liver enzymes systems are not fully
developed until ___ \_\_\_\_\_\_\_ of age
very young, 3 months
53
The ability to synthesize liver enzymes may be impaired in _____ animals thus decrease the capacity to \_\_\_\_\_\_\_.
old, metabolize
54
Malnourished animals cannot synthesize enough ______ enzymes needed for metabolism
liver
55
Many liver diseases such as \_\_\_\_\_\_\_\_, ______ \_\_\_\_\_\_, and ______ inhibit the CYP450s
hepatitis, liver cirrhosis, cancer
56
Hyperthyroidism may increase the _____ of metabolism of drugs while hypothyroidism does the \_\_\_\_\_\_\_
rate, opposite
57
When administering a drug metabolized by the liver, it is wise to anticipate a drug _______ if a second drug also metabolized by the liver is added to therapy.
interaction
58
Induction of drug-metabolizing enzymes should be considered as a ________ mechanism that
facilitates excretion of potentially ______ compounds
protective, toxic
59
Inducers generally act as _______ for the induced enzymes and the induction is ____ dependent
substrates, dose
60
Inducers often induce more than ____ \_\_\_\_\_\_.
one CYP
61
Maximal induction generally requires ___ to ___ hours of exposure to a drug. It can return to baseline
\_\_\_ to ___ hours (depending on dose) after the inducer is discontinued.
10, 12, 18, 24
62
Barbiturates are recognized inducers of \_\_\_\_. _______ is one of the most potent microsomal
enzyme inducers known and can enhance the _________ of other ________ drugs.
CYP, Phenobarbital, hepatotoxicity, hepatotoxic
Metabolites can be toxic; if they accumulate in the liver; metabolites go back through first pass metabolism?
63
Drug interactions that reflect ________ of _____ may be at greater risk of causing serious
adverse events
inhibition, enzymes
64
As with inducers, the extent of inhibition is ?
dose dependent
65
Inhibitors often act as _______ at the inhibited enzyme
substrates
66
Currently, three types of inhibitors have been described: ?
reversible, quasireversible and irreversible
67
\_\_\_\_\_\_\_\_, ______ and ______ \_\_\_\_\_ drugs are examples of potent enzyme inhibitors
Chloramphenicol, cimetidine, imidazole, antifungal
68
\_\_\_\_\_\_\_\_\_\_ inhibits CYP enzymes including CYP3A4 in dogs
Ketoconazole
69
Drug-induced inhibition of drug metabolism can be used for ?
therapeutic benefit
70
Ketoconazole interferes with the ________ of drugs that are metabolized via \_\_\_\_\_\_\_. It has
been used to ______ blood drug concentrations of _______ in dogs and cats (reduce
dosage/cost).
metabolism, CYP3A, increase, cyclosporine
71
\_\_\_\_\_\_\_\_ has been used to prevent metabolism of acetaminophen in ______ and ______ into potentially lethal toxic metabolites.
Cimetidine, humans, cats
72
Cilastatin inhibits the metabolism of _______ by ________ \_\_ on the brush border of _____ \_\_\_\_\_ cells.
imipenem, dehydropeptidase, I, renal tubular
73
Renal excretion is the most important route of drug ________ for both ______ (especially \_\_\_\_\_
soluble) drugs and their \_\_\_\_\_\_.
elimination, parent, water, metabolittes
74
The kidney has been the most widely studied excretory organ because of the accessibility of \_\_\_\_
to collection and analysis.
urine
75
Host factors that determine renal excretion include
* Renal blood flow (glomerular filtration)
* Active tubular secretion
* Tubular (generally passive) reabsorption
76
Total renal excretion of a drug = ?
𝑹𝒂𝒕𝒆 𝒐𝒇 𝒇𝒊𝒍𝒕𝒓𝒂𝒕𝒊𝒐𝒏
+ Secretion - reabsorption
77
78
The glomerular filtration is a ______ process. Drugs enter the glomerulus from the _____ by ____ flow. Too large drugs (\> ______ MW) are excluded as occurs for \_\_\_\_\_-bound drug if the glomerulus is \_\_\_\_\_\_\_.
passive, blood, bulk, 60,000, protein, healthy
79
80
Active transport of drugs in the ______ tubules is a very efficient and rapid process. It is susceptible
to _______ between drugs. Separate ______ transport systems exist for acid, basic, and neutral
drugs (\_\_\_\_\_\_\_\_,\_\_\_\_\_\_\_\_,\_\_\_\_\_\_\_). It is not limited by _____ binding.
proximal, competition, active, p-glycoprotein, OATPs, POTs, protein
81
The transport systems across tubule cells involves _____ \_\_\_\_\_\_\_\_\_ _____ of transport proteins. One set is located in the _____ \_\_\_\_\_ and the other is located in the ________ \_\_\_\_\_\_\_.
two, separate, pairs, brush, border, basolateral membrane
82
There are two distinct secretory pathways in the later sections of the _______ renal tubule: one for _______ (?) and one for ____ compounds (?)
proximal, acidic, organic anion transporter/OAT, basic, organic cation transporter/OCT
83
The primary orientation of this system is from _____ to tubular \_\_\_\_\_, ______ drugs and/or metabolite _______ from the \_\_\_\_\_.
blood, filtrate, removing, conjugates, blood
84
85
Many drugs compete for the same ______ \_\_\_\_\_\_\_ sites, leading to drug interactions. This interaction has been studied with the ______ \_\_\_\_ transport system.
tubular transport, organic acid
86
Weak acids such as ________ or __________ will inhibit secretion of the _____ \_\_\_\_\_\_ penicillin, thereby prolonging the ______ concentration of penicillin.
probenecid, phenylbutazone, weak acid, blood
87
Do we need to know this slide?
88
Reabsorption of drugs from renal _____ into ______ capillaries slows renal \_\_\_\_\_\_.
tubules, peritubular, excretion
89
The drug reabsorption depends on its ?
lipid solubility and its ionization
90
\_\_\_\_\_\_ _____ drugs are more likely to be reabsorbed in _____ urine but are trapped and
excreted in ______ urine
Weakly acidic, acidic, alkaline
91
A brisk, alkaline diuresis is induced to decrease ________ \_\_\_\_\_\_\_ into the blood and ________ excretion into the \_\_\_\_
salicylate reabsorption, accelerate, urine
92
Difference in pH can have a major influence on the ____ of renal excretion
rate
93
Carnivores tend to have a more _____ urine (pH ?) than herbivores (pH ?).
acidic, 5.5-7.0, 7.0-8.0
94
A weakly acidic drug will have a _______ renal excretion
higher, Herbivores \> carnivores
95
A weakly basic drug will have a _______ renal excretion
higher, Carnivores \> herbivores
96
In healthy animals, small changes in urinary pH or urinary flow rate do not significantly contribute
to ?.
altered drug clearance
97
Urinary pH can be therapeutically altered such that the renal _______ \_\_\_ of a drug can be modified ( _______ or \_\_\_\_\_).
excretion rate, overdose, toxicity
98
Because phenobarbital is \_\_\_\_\_\_, ________ the
urine increases clearance about _____ fold.
acidic, alkalinizing, five
99
100
Drugs excreted in the urine that do not undergo _______ reabsorption will be \_\_\_\_\_\_\_\_\_
concentrated in the renal tubule
passive, progressively
101
\_\_\_\_\_\_\_ cells may be exposed to higher concentrations of drugs, which may increase the risk of \_\_\_\_\_\_\_\_.
Tubular, nephrotoxicity
102
Drug concentration in the urine can be of therapeutic benefit in some situations such _______ \_\_\_\_\_\_.
bacterial cystitis
103
At ____ urine flow rates, there is greater opportunity for ______ of drug from the _____ tubular fluid back into the \_\_\_\_\_.
low, diffusion, distal, blood
104
Diffusion is facilitated by the _____ concentration of drug in the ______ fluid
high, tubular
105
Polar compounds having ____ \_\_\_\_\_ solubility (such as many drug \_\_\_\_\_\_\_) are not ______ since they cannot cross the ____ \_\_\_\_\_\_.
low lipid, metabolites, reabsorbed, lipid membrane
106
Active reabsorption systems are also present in order to act on a drug already present in the _______ load and recover ______ \_\_\_\_\_ (e.g., \_\_\_\_\_\_\_)
filtered, essential nutrients, glucose
107
Some drugs reach their target sites by the mechanism of active reabsorption, making their ____ more important for predicting ______ than their _____ concentration. Example: ?
TFC, activity, blood, the diuretic
furosemide
TFC = tubular fluid concentration
108
Furosemide is first secreted by the _______ into tubular ____ and than is actively \_\_\_\_\_
back into _____ cells to gain access to its receptors for activity.
tubules, fluid, reabsorbed, tubular
109
110
Most of the Phase I and Phase II enzymatic systems present in the liver also exist in the \_\_\_\_\_\_.
Oxidative processes generally occur within the _____ \_\_\_\_\_ cells.
kidney, proximal tubule
111
In the case of renal drug biotransformation, what two scenarios might occur?
* A drug is solely metabolized by the kidney and not the liver
* The kidney metabolizes a drug already biotransformed by the liver, relay metabolism
112
Morphine and acetaminophen are also metabolized by the \_\_\_\_\_
kidney
113
The ultimate route for drug elimination from the body is the \_\_\_\_\_\_\_.
kidney
114
Drugs can also be eliminated in ? (7)
What is the significance, if any, of these elimination sites?
bile, milk, saliva, expired air, feces, sweat, and tears
For most therapeutic drugs these routes are generally not quantitatively important for reducing total body burden of drug.
115
Biliary excretion is very _____ and much ____ clinically important
slow, less
116
What factors determine biliary excretion?
Chemical structure, polarity, and MW of drugs (drugs \> 600 MW in size) determine this excretion.
117
Drugs excreted in the bile are in big contact with the ?
intestine and its flora
118
The contact with intestine is more likely to cause ?
adverse reactions in the GI-tract
119
Conjugated (Phase II) drugs excreted by ______ excretion may undergo enterohepatic circulation
biliary
120
Intestinal bacteria ________ the drug or metabolite, allowing _______ absorption to occur
unconjugate, intestinal
121
Enterohepatic circulation can prolong the _________ \_\_\_\_-\_\_\_\_\_ of a drug
elimination half-life
122
After ______ or ______ administration the drug is
conjugated in the liver and eliminated in the bile
oral, parenteral
123
Degradation results in ________ of drug, which can then be \_\_\_\_\_\_\_\_.
deconjugation, reabsorbed
124
125
Drugs enter the saliva by ______ diffusion from the \_\_\_\_\_\_.
passive, blood
126
Salivary excretion is important in _______ receiving ______ antimicrobial drugs.
herbivores, parenteral
127
Copious salivation by _____ and _____ and the swallowing of antimicrobial-drug-laden saliva
may upset the _______ process in the rumen.
cattle, sheep, digestive
128
The expired air route of excretion is primarily important for ______ drugs including ____ \_\_\_\_\_\_ drugs
volatile, gas anesthetic
129
True or False: Excretion via milk **IS** a major route of drug excretion.
False. Excretion via milk is not a major route of drug excretion.
130
Drug excretion via milk is important if the milk is to be used for human ________ (requiring a _______ period).
consumption, withdrawal
131
\_\_\_\_\_\_\_ ____ drugs will tend not to distribute into the milk after systemic distribution.
(e.g., penicillin), while weakly basic drugs will (e.g., erythromycin)
Weakly acidic
132
Plasma pH = \_\_\_; Milk pH = \_\_\_\_\_\_
7.4, 6.5-6.8
133
Drugs that are _____ absorbed after ____ administration or drugs that are secreted _______ into the intestine or into ___ are excreted in the \_\_\_\_\_\_
not, oral, directly, bile, feces
134
What are the minor routes of excretion?
Tears and sweat
135
136
The combined effects of hepatic _______ and ______ and ______ excretion, as well as other routes of elimination irreversibly clear the drug from the body.
metabolism, renal, biliary,
137
Pediatric generally refers to the first __ weeks of life.
12
138
Drug disposition in the pediatric animal: At what age is an animal considered to be a neonate?
0-2 weeks
139
Drug disposition in the pediatric animal:
What age range is an animal considered to be an **Infant**?
(\> 2 to 6 weeks)
140
Drug disposition in the pediatric animal:
What age range is an animal considered to be **Pediatric**?
> 6-12 weeks
141
Pediatric patients exhibit:
1. Decreased hepatic ______ capacity
2. Immature ______ function
3. Decreased _____ and renal \_\_\_\_\_\_\_
metabolic, biliary, GFR, clearance
142
Drug _________ , including both ____ metabolism and ______ excretion is limited in _______ and ______ patients
elimination, hepatic, renal, neonatal, pediatric
143
Many drugs administered to the young animal are characterized by _______ \_\_\_\_\_ clearance (until __ to \_\_\_\_\_), and _____ half-life
decreased renal, 2, 3, months, longer
144
In pediatric patients, hepatic metabolism of drugs is \_\_\_\_\_\_. Both phase I and II reactions are \_\_\_\_\_\_\_.
deficient, reduced
145
Although glomerular filtration and renal tubular function progressively _________ , adult values may not be reached until approximately ___ \_\_\_\_\_ of age
increase, 2.5, months
146
Renal tubular reabsorption in ______ appears to be similar to that in _____ as long as body ______ and _______ are maintained
puppies, adults, fluids, electrolytes
147
Clearance is a pharmacokinetic parameter describing drug \_\_\_\_\_\_\_\_
elimination
148
Clearance is defined as the volume of _____ which contains the ____ amount of drug that is _______ from the body in ____ time
plasma, total, removed, unit
149
Clearance is expressed as ?
volume per unit time, e. g., mL/min or L/h
150
Cleareance is often used to assess the ?
excretory capacity of an organ (kidney)
151
Renal clearance (Clrenal)is defined as the volume of ______ containing the amount of drug that is _______ from the body by the ______ in ____ time
plasma, removed, kidneys, unit
152
What is the CLrenal formula?
153
Usually ____ and ____ clearance are the most important.
renal, hepatic
154
The _______ clearance of a drug or ____ \_\_\_\_ clearance (CLtotal) is the ____ of clearance ____ for each mechanism involved in ______ the drug
overall, total body, sum, rates, eliminating
155
Cl other means what?
Other forms of excretion
156
Clearance is used to determine the rate of ?
drug elimination
157
Clearance is the _________ \_\_\_\_\_\_ to determine the rate of drug elimination
proportionality factor
Why? B/c if clearance is high rate of elimination is high.
158
Clearance does not describe the ______ of drug being eliminated
amount
159
160
Rate of drug elimination is the _______ of drug being _____ per ____ time
amount, eliminated, unit
How much drug is being eliminated in the body
161
The overall clearance CLtotal can also be estimated by measuring _____ concentrations at ______ following a ____ \_\_\_\_\_ bolus dose (Q mg)
plasma, intervals, single, intravenous
162
163
AUC0 −∞ is the area under the full curve relating Cp to time following a bolus dose given at time t = 0
164
AUC0 −∞ provides an integrated measure of _______ exposure to the drug in units of time _______ by drug concentration
tissue, multiplied
165
Drug clearance can also be determined in an individual subject by measuring the ______ concentration of the drug ( mg/L) at intervals during a \_\_\_\_\_-rate ______ infusion (X mg of drug per hour)
plasma, constant, intravenous
166
167
168
Css is the plasma drug concentration at a _____ \_\_\_\_.
steady state
169
Knowing the clearance enables one to calculate the _____ \_\_\_\_ needed to achieve a desired \_\_\_\_\_-\_\_\_\_\_ ("target") _____ concentration.
dose rate, steady-state, plasma
170
During a constant intravenous infusion at rate X mg/h, the plasma concentration _______ from ____ to a \_\_\_\_\_-state value (\_\_\_\_); when the infusion is \_\_\_\_\_, ___ declines to zero
increases, zero, steady, Css, stopped, C
171
Constant intravenous infusion
172
Following an intravenous bolus dose (Q mg), the plasma concentration rises _____ and then declines towards \_\_\_\_\_
abruptly, zero
173
IV bolus
174
Data from panel (B) plotted with plasma concentration on a logarithminc scale. The straight line shows that concentration declines exponentially
175
Elimination T½ refers to the _______ of drug from plasma.
disappearance
176
Elimination half-life (T½) is _____ relevant and the most often reported _______ parameter
clinically, pharmacokinetic
177
Elimination T½ is defined as the _____ necessary for _____ or ____ concentrations to ______ by 50%
time, plasma, blood, decline
178
For example, at one drug half-life, 50% of the dose has been eliminated; after five T ½s (half-lives) 97% of the drug has been eliminated
179
The more rapidly a drug is cleared by an organ, the ______ the drug half-life
shorter
180
The longer the half-life, the _____ the drug will persist in the body
longer
181
Any factor that changes the ___ of a drug will affect its half-life
Vd
182
An increases of ___ can increase the half-life and _____ the duration of action of the drug
Vd, extend
If the Vd is low? the plasma concentration is high.
Vd means?
High Vd = ?
183
Elimination half-life along with the dosing interval also determines the _____ of drug that _____ with each dose as \_\_\_\_\_-state equilibrium is reached
amount, accumulates, steady
184
Along with the ______ range, the \_\_\_\_-\_\_\_ should be the basis for an appropriate dosing interval
therapeutic, half-life
185
Half-life (T½) of a drug is increased by:
* Decreased renal or hepatic blood flow: Hemorrhage, heart failure, cardiogenic shock
* Decreased renal function
* Decreased metabolism: Another drug inhibits its biotransformation, hepatic insufficiency; How?
186
Half-life (T½) of a drug is decreased by:
* Increased hepatic blood flow
* Decreased protein binding. Why? Protein binding stops capacity of drugs to go to the tissues.
* Increased metabolism
187
Anything that changes the _____ of ______ of a drug will affect its half-life (T½)
volume, distribution
188
Many drugs exhibit \_\_\_-order kinetics
first
189
The most common, note if elimination mechanisms become \_\_\_\_\_\_, elimination becomes \_\_\_-order
saturated, zero
190
If a drug half life is 2h, how long does it take the body to completely eliminate the drug?
After first half life, 50%, second = 25, after 5 = 97%
Ever 2 hours, 50% of the drug is eliminated.
191
The volume of blood cleared per unit time by an organ is _______ of PDC
independent
192
In first order elimination, the ____ volume of blood will be irreversibly cleared of drug by an organ regardless of how much drug is in the blood.
same
193
In first order elimination, a _____ \_\_\_\_\_ is eliminated per unit time. \_\_\_% of drug per hour. The half-life (T½) of a drug will be constant regardless of ___ \_\_\_\_\_\_
constant, fraction, 50, drug concentration
194
The first half life is the same as the second in time in the case of first order elimination
195
\_\_\_\_\_\_-order elimination is less common.
Zero
196
Zero-order elimination only occurs when so much drug is present in the blood that the organ of clearance becomes \_\_\_\_\_\_
saturated
197
Zero-order elimination occurs when there is ______ amount of enzyme and ____ \_\_\_\_ of the drug.
limited, too much
198
The rate of elimination of a drug from the plasma is _____ regardless of the _____ \_\_\_\_\_ of the drug.
constant, plasma concentration
199
In zero-order elimination, the \_\_\_-\_\_ is not meaningful. It is ___ constant and varies with the amount of the _____ \_\_\_\_\_\_.
half-life, not, drug concentration
200
Half life is always constant in first order elimination
201
In the case of ethanol, the time course of disappearance of drug from the _____ is eliminated by \_\_\_\_-order elimination.
plasma, zero
202
The rate of elimination of ethanol from the plasma is \_\_\_\_\_\_, regardless of ___ or of _____ concentration of ethanol
constant, dose, plasma
203
Half life is not constant in zero order elimination
Rate of elimination is constant
204
Pharmacokinetics provides a framework for understanding _____ \_\_\_\_\_\_ ____ when given to an animal or human**,** ___ \_\_\_\_ ___ \_\_\_ \_\_\_, and how quickly, that enables one to understand the effects that it produces
what happens to a drug, where it goes in the body
205
In practice, pharmacokinetics usually focuses on ?
concentration of drug in blood plasma
206
Plasma concentrations are used in routine clinical practice to ?
individualize dosages
207
To achieve the desired therapeutic effect while minimizing adverse effects in each individual patient- an approach that known as ? can be used
therapeutic drug monitoring, TDM
208
\_\_\_-\_\_\_\_\_\_\_\_\_ is used to predict the behavior of a drug in the body
PK-modeling
209
Generally the drug of interest is given at the desire route of administration as a ____ dose
single
210
Drug concentrations (samples) are collected _____ \_\_\_\_\_, preferably for at least ______ elimination half-lifes to ensure that all phases of drug _______ are identified
over time, three, movement
211
For bioavailability studies, the drug should be given ______ (100%) as well as by the route of \_\_\_\_
intravenously, interest
212
The most common described in the veterinary literature are either ?
compartmental or noncompartmental analysis
213
The body is considered as consisting of a _____ \_\_\_\_\_\_ compartment. That is, the entire dose X of drug is assumed to move ___ of the body at a ____ rate
single homogenous, out, single
214
The Single- or one compartment model is applicable if the _____ concentration falls ________ after drug administration.
plasma, exponentially
215
After drug administration, drug is absorbed, and then in one single compartment our whole drug. After that there is constant excretions and metabolism
216
The two-compartment model introduces a ______ \_\_\_\_\_ compartment to represent the \_\_\_\_\_, in communication with the _____ \_\_\_\_\_ compartment.
separate, peripheral, tissues, central plasma
217
The two compartment model more closely resembles?
The real life process
218
The two compartment model is a widely used approximation in which the _____ are lumped together as a _____ compartment
tissues, peripheral
219
In the two-compartment model, drug molecules can ____ and ____ the peripheral compartment only via the ____ compartment
enter, leave, central
220
Distribution rate constant (\_\_\_\_) out of the ____ compartment
K12, central
Goes to the peripheral compartment
221
Redistribution rate constant (\_\_\_\_) from the _____ back into the ____ compartment
K21, peripheral, central
We need to it to goto central compartment again to be excreted and metabolised.
222
223
The multi-compartmental model is generally employed when experiments are conducted over ____ times frames.
long
224
The multi-compartmental model may be used if the goal of a study is to to describe the tissue _____ of a drug in a ____ \_\_\_\_\_ animal
residue, food producing
225
These compartments have specific equations to calculate clearance
226
227
Protein-bound drugs can be secreted by _____ tubular secretion, but can not be eliminated by _____ \_\_\_\_\_.
Passive reabsorption- ___ solubility matters
\_\_\_\_ is not a root of excretion
active, renal glomerulus, lipid, fat
