Exam 1A: Dr. Owens Flashcards
1
Q
Parenteral route literally means “other than enteral”, but generally reserved to describe routes when drug is administered by _____.
A
hypodermic injection. (parenteral routes avoid epithelial barriers)
1
Q
Passive diffusion is quantified by ____.
A
Fick’s First Law of Diffusion
1
Q
This means that molecules can come apart.
A
Ionization. Note: Some drugs can ionize into charged particles.
1
Q
Value of f which means the drug is highly bound.
A
f < 0.1 (e.g. 90%)
1
Q
PK media collection: Biological samples are generally stored in freezers at ____ (temperature)
A
-20C or -80C
2
Q
Drug tolerance develops to the action of many CNS drugs like (3)
A
- Opioids 2. Antipsychotics 3. Antidepressants
3
Q
Elimination of a constant quantity per time unit of the drug quantity present in the organism.”
A
Zero order elimination. (Linear graph)
4
Q
Refers to as what the body does the drug does to the drug.
A
Pkinetics
5
Q
This is referred to drug loss sue to large amount of blood flow that goes through the liver from the GIT.
A
First pass
6
Q
2 Parameters needed to determine therapeutic window
A
- efficacy 2. safety
7
Q
FYI: Protein Binding is described as a FRACTION.
A
:P
8
Q
The ________ model frequently accounts for PD effects and describes that the effect may be saturated.
A
Emax
9
Q
Gives information about rate of absorption
A
Cmax = maximum concentration
9
Q
This is the negative of the slope.
A
k value. It tells you the half life of the drug.
9
Q
T/F: PK models are built to describe a system mathematically and depend upon assumptions made about the system. Any lack of adherence of the real system to the assumptions will lead to loss of accuracy in predictions of the model
A
T
10
Q
These are used to quantify the time-course of drug concentrations in the body.
A
PK models
10
Q
In Mammillary models, elimination occurs from the ________, reflecting that the kidneys and liver are highly perfused tissues.
A
central compartment
11
Q
This is the elimination rate constant, gives information about the elimination rate.
A
k
11
Q
Orally absorbed drug passes through the gut wall, passes through the liver before entering the systemic circulation thereby subject to a grater fractional loss of drug.
A
First-pass metabolism
12
Q
This is the proportionality between concentration and amount.
A
Volume distribution (Vd)
12
Q
PD response to a drug may be (2)
A
- Rapid: (Neurotransmitters, Neuromuscular blockade, drug effects on electrical signals) 2. Delayed: ( Hormone effects, mRNA effects, protein or enzyme changes, antibiotic effect, wt. loss, bone density, smoking cessation) or response may be inhibitory or stimulatory
13
Q
This enzyme show 50% of Whites are extensive metabolizers.
A
CYP - 2D6
14
Q
It describes the sum of elimination from all routes (e.g. renal and hepatic)
A
Total body clearance (ClT)
15
Q
It is the hypothetical volume of body fluid from which a drug is completely removed per unit time.
A
Clearance
16
The route of administration influences the _________ of drug in the body.
concentration-time profile
17
Disposition is composed of (3)
DME 1. Distribution 2. Metabolism 3. Excretion
18
Nonsystemic (local route): Drugs merely has to stay at the site of action, or travel a short distance by ______ or ______ to reach its site of action.
1. diffusion 2. absorption through tissue
18
This is a product of the formulation and the regimen administered.
Exposure
19
Practical considerations in Polymorphism in PK (3)
1. Dose Adjustments 2. Dose Amount 3. Dosing Interval
20
In Local routes, high concentrations can be achieved. Systemic concentrations may occur, but they are \_\_\_\_\_\_. Systemic concentrations resulting from local administration may be a source of \_\_\_\_\_\_\_.
coincidental........ unintended adverse effects.
21
Administering a bolus and an infusion in order to achieve the steady state.
Loading Dose
23
This refers to the rate of decline (elimination) depends on how much drug is present at that time. The IV Bolus concentration falls in this type of process.
First order elimination
24
The ability of the drug to go in solution is affected by the
surface area.
24
In Mammillary models, other compartments represent collections of other tissues with slower distributional characteristics - e.g. (3)
1. Bone 2. Brain 3. Adipose
25
Tis is the simplest PK model.
One Compartment Model with IV Bolus Admin
25
This is an example of a high Volume distribution.
Digoxin
25
This reflects how strongly drugs bind to plasma proteins.
Affinity (Kd)
25
Practical considerations in PD (2)
1. Diagnostics for treatment selection 2. Treatment algorithms
26
PK properties do not change with changes in concentration; aka "dose proportional PK", "proportionality to kinetics"
Linearity
27
Variables in Cockcroft and Gault method (3)
1. Age 2. weight (kg) 3. Serum cratinine
28
How well a drug product mixes, or goes into solution, depends in part on whether it is a(an) \_\_\_\_\_.
electrolyte
30
Route of Administration: Administered drug reaches and travels through the general circulation in order to gain access to its target site of action.
Systemic Distribution
32
Refers to as what the drug does to the body.
Pdynamics
33
Example of a drug that has nonlinear PK.
Dilantin. (If you double the dose, you get much proportional levels; can lead to toxicity) AUC increases supra-proportionally with dose
34
This PK models have a central compartment, and all other compartments connect directly to the central compartment, with REVERSIBLE flow between compartments.
Mammillary model
36
FYI: ER tabs may be seen in stools.
:)
36
GIVE 5 examples of organs of excretion.
Kidneys, gall bladder sweat glands, mammary glands lungs
36
It gives information about the total extent of absorption
AUC = Area Under the Concentration-time curve
37
pH of urine which favors treatment of methamphetamine toxicity.
Acidic (Low pH). Increases excretion and shortens 1/2 life
38
3 Mechanisms for Genetic Factos of Drug Response.
Polymorphisms in 1. Drug Receptors 2. Drug Transporters (e.g. MDR1) 3. Drug Metabolizing Enzymes (e.g. CYP 2D6)
39
This is the ratio of CSF to unbound drug in plasma
Equilibration of drug in the CSF
40
Mechanism of transport at the tubular level (secretion and reabsorption)
Active/ Facilitated processes
41
Polymorphisms in drug receptors alter \_\_\_\_
drug binding and action
42
Part of nephron where drug secretion occurs
Proximal convoluted tubule.
42
This can alter absorption, distribution, or even efficacy and safety when transporters keep the drug away from the site of action or metabolism.
Polymorphism in Drug Transporters
42
This is the first observed polymorphism in drug metabolizing enzymes.
CYP 2D6
44
This route gives the provider the most control or manage the drug.
Continuous IV infusion
45
Clearance units are expressed in \_\_\_
volume per time (e.g. L/ Hr)
45
Major routes of drug elimination - % (8)
1. CYP 3A4: 28% (Phase 1) 2. Renal: 25% 3. UDPG: 10% (Phase 2 Glucurunidation) 4. CYP 2D6: 10% 5. Other Metabolism: 10% 6. CYP 2C9: 7% 7. Hepatobiliary: 6% 8. Other CYPs: 4%
46
This treats the body as one homogeneous volume in which mixing is instantaneous. Input and output are from this one volume. Drug goes in and concentration is uniformed all through out.
One Compartment model
46
Letter that symbolizes bioavailability.
F
47
Drugs recycled and excreted from bile are metabolized during phase II, like ____ .
glucuronidation
49
"open" compartmental models have ______ from the system.
elimination
50
This happens when drug is not highly bound.
Dissociation
51
Metabolism and excretion is collectively called \_\_\_.
Elimination
52
Clearance is the product of
V (volume distribution) and K (rate of elimination)
53
Pharmacogenetic factors have highest impact on these drugs (3)
1. Psychoactive drugs 2. CV drugs 3. Cancer drugs
54
Mechanism of transport: Filtration at the glomerular capillary
Passive transport
56
What is the concentration-time profile for intermittent IV infusion?
Saw-tooth pattern.
57
True or False: Absorption still must occur for SC, IM, and intraperitoneal administration.
true
58
When effect is plotted against concentration, different responses are seen at the same concentration; graph shows a loop.
Hysteresis
59
Other name for "open" compartmental model
Multicompartmental model
60
Enzymes that are important in Phase 1 (3)
2C9 2C19 2D6
62
T/F: Charged molecules typically can't cross the lipid bilayer.
true
63
Drugs can be eliminated before absorbed by the body by __ (3)
HCG 1. Hepatic Metabolism/ 1st pass 2. Chemical degradation 3. GI metabolism
64
Noncompartmental Analysis (NCA) Parameters (4)
Cmax, Tmax, k, AUC
65
These (2) define relationship between concentration and effect of most drugs.
1. Emax (Max effect) 2. C50: Concentration achieving 50% maximal drug effect
66
Initial passage of drugs through the liver
First Pass metabolism
67
Oral drugs absorbed through the gut wall flows into the \_\_\_.
portal vein to the liver.
68
This PK models are similar to mammillary compartmental models, but one to more compartments do not connect directly to the central compartment.
Catenary Models
69
What happens when you take simvastatin with grapefruit juice?
It blocks3A4 and PGP therefore it increases AUC and decreases clearance.
70
PK/ PD models can "\_\_\_\_\_\_", when they appropriately describe the mechanism or time-course of the hysteresis.
collapse the hysteresis
71
PK medium where cellular fraction is used. The use of anticoagulant like heparin or EDTA is used to prevent clotting.
Plasma
73
Bioavailability is described in terms of (2)
Rate and Extent of Absorption
73
Examples of Dosage Regimen Designs (2)
1. Therapeutic Range 2. Therapeutic Window
75
Enterohepatic recycling can occur. The highest concentration of reabsorption occurs in the \_\_\_\_\_, where there is increased villi surface area.
duodenum.
76
In intermittent IV infusion profile, the peaks refer to the \_\_\_\_
end of infusion.
78
This is the ability of a drug to get into the systemic circulation from the site of administration.
Bioavailability
79
This is termed for induction or inhibition of PD responses. It results in a change of PK/PD relationships overtime.
Functional Adaptation
79
This is the study of individual variations in drug response due to genetic variations.
Pharmacogenomics
81
Processes (or phases) of pharmacokinetics (4).
ADME 1. Absorption 2. Distribution 3. Metabolism 4. Excretion
83
In continuous infusions, this refer to the balance between drug going in and drug going out. This leads to constant plasma concentration level.
steady state.
84
PK Media Collection (4)
1. Whole Blood 2. Serum 3. Plasma 4. Urine
86
T/F: Parenteral route has either local or systemic effects.
True
87
Elements of a Regimen (3). These are the things we control in a regimen.
1. Route 2. Dose 3. Frequency
88
This model refer to time zero drug is evenly distributed in the body.
Well-stirred Model
88
PK medium where in the clotting facts and cellular components are removed.
Serum
89
Parameters (3) used in Hill Equation (Drug Effect Calculation)
1. Emax (Max effect) 2. C50: Concentration achieving 50% maximal drug effect 3. C: Unbound drug concentration
90
Part of nephron where drug reabsorption occurs.
Distal convoluted tuble
91
PK Sources of Drug tolerance
Increase or decrease in metabolic activity
92
This can cause non-linearity
Saturation of drug metabolizing enzymes
94
These transporters cause INTESTINAL EFFLUX. It takes out the drug molecule out of the blood stream and throw it back to the GIT. (2)
1. MDR1 or PGP (P-glycoprotein) 2. BCRP
95
Causes of Functional Adaptation (3)
1. Desensitization of receptors 2. Up/ down regulation (feedback) 3. Precursor pool depletion
97
T/ F: The magnitude of the apparent Vd does NOT always have a true anatomical or physiological interpretation because of the interactions that may occur in the body.
True
98
The site of action and pathways of response could be immediate or prolonged due to \_\_\_\_
pharmacodynamic events or time-delays
100
2 Assumptions of One Compartment Model
1. Rapid equilibration of drug throughout the body ("well-stirred") 2. First order elimination
100
Refers to the functional adaptation of the effect. (Does the kinetic/ dynamic system change overtime?)
Stationarity
102
Down side of Continuous IV infusion.
Titrate the drug and its effects
103
This term refers to drugs metabolized or changed into another compound by the liver. It can be an active compound (could have adverse effect or toxicity) and can be further metabolized by the liver, or excreted.
Metabolites
104
These (2) may drive the time-course and extent of DRUG EFFECTS.
1. Total exposure 2. time-course of drug concentrations
106
Drugs must cross membranes in order to reach their sites of action. The most common process is by \_\_\_\_.
passive diffusion
107
This is the amount of time for the drug concentration fall by half.
half-life
108
The elimination of drug is proportional to the drug concentration.
First order elimination
108
This PK Medium contains cells and clotting factors. They are more difficult to work with.
Whole Blood
109
The behavior of the drug in the body depends on (4)
1. chemistry of the drug molecule 2. chemistry of the local environment 3. Physical properties of the local environment 4. Anatomy and physiology of the local environment.
110
Route of Administration: Drug is administered at or near the site of its intended action. (there are chances of systemic distribution though)
Nonsystemic (Local) Use
112
This refers to the time course of drug concentrations in the body.
Pharmacokinetics
113
What happens when PGP or MDR-1 is active?
It moves drug from the blood stream back to the GIT. Therefore there is less exposure to the drug.
114
This PK modesl view the body as a collection of compartments that have drug transfer between compartments.
Compartment model
115
Co (initial concentration), can be seen that the fraction of the original concentration that remains is described by:
e, to the - kt
116
This reflects that drugs may not get into every tissue to the same extent.
tissue permeability limitations
117
This states that BOUND DRUG is generally not available for distribution, metabolism, or for exerting an effect in the body.
Free Drug Hypothesis
118
The release of drugs happen at different intervals. There is continuous absorption of drugs.
Extended-release formulation.
119
PD sources of Drug Tolerance
Increase or decrease in number of receptors
121
Drug elimination can alternatively be described in the context of \_\_\_\_\_.
clearance
123
Example of autoinducer drug.
Modafinil
124
T/F: Many drugs are weak electrolytes. Weak acids or bases. Very few are strong electrolytes.
True
125
Symbol for initial concentration.
Co
126
Multiplier used in calculating Creatinine clearance in females.
.85
127
Metabolism of drugs most occur in the
liver
128
Passive diffusion depends on appropriate _____ in the membrane barrier components.
solubility
129
What is the goal of pharmacogenomics?
to individualize therapy
130
Type of drug release for oral sustained-release drugs.
Zero-order release or Infusion-like release
132
For a drug substance to be available for absorption, it generally must be \_\_\_\_.
in solution at the site of absorption
133
This is the estimate of kidney function.
Estimated creatinine clearance
134
Drug excretion occurs in what organs in the body? (2)
1. Kidneys (renal) 2. Gallbladder (biliary)
135
The amount eliminated per unit time is dependent upon the amount present at that time.
First order elimination
137
FYI: Protein Binding 1. Can be become saturated for some drugs 2. There can be multiple binding sites per protein molecule for some drugs.
:D
138
Gives information about the time of the peak concentration.
Tmax
139
Oral drugs can be absorbed at the gut wall and be metabolized due to high concentration of which enzyme?
Cytochrome P 450 - 3A4
140
The peak concentration of IV Bolus occurs \_\_\_\_
right after administration of drug.
141
In Mammillary models, the central compartment represents the (2)
1. Vascular spaces 2. Any highly perfused, rapidly equilibrating tissues.
143
Method used to measure estimated renal clearance
Cockcroft and Gault Method
144
Drugs doses can enter the blood through (2)
1. Extravascular dose (orally, transdermal, rectal, etc..) 2. IV dose
145
Tolerance to Nitroglycerine develops within \_\_\_.
a day. Reminder: Have off periods during the day
146
Polymorphisms in drug metabolizing enzymes may lead to different population who are ___ (3)
1. Poor metabolizers 2. Extensive metabolizers 3. Ultrarapid metabolizers
147
Name of the formal in calculating Drug Effect (E)
Hill Equation
148
These are predictors of PK. This is how we individualized doses.
Covariates
149
Referred to as unwanted safety risks.
Adverse effects
