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Fundamentals of Medicine: Exam II > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Pharmacodynamics is _______
Pharmacokinetics is _____

A

What the drug does to the body

What the body does to the drug (absorption, distribution, metabolism, elimination ADME)

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2
Q

If a drug is bound to ______ protein it can’t move across membranes and be distributed to other tissues

A

Plasma

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3
Q

_____ is helpful to determine the best route of administration and the best choice of dosing

A

Pharmacokinetics (PK)

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4
Q

The first thing a drug encounters to gain excess to cells is the _____ _____. If a drug is ______ it will not cross the membrane as well. _____ drugs will cross the membrane easier

A

Plasma membrane

Hydrophilic
Hydrophobic

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5
Q

____ ____ ____ is the factor that calculates how likely a drug will hangout in octanol phase versus the aqueous phase. Drugs with _____ LPC prefer the octanol phase. Drugs with ____ LPC typically cross the membrane more efficiently.

A

Lipid partition coefficient
Higher
Higher

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6
Q

Free ____ won’t readily cross a lipid membrane. But the _____ form of a drug has solubility with the lipid membrane

A

Ions
Neutral

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7
Q

A ____ ____ is a proton donor, these are lots of drugs. They exist in the plasma as protonated (neutral) and anion forms in equilibrium. ____ does not cross the membrane but _____ does, especially in the stomach were there is a low ____ .

A

Weak acid
Anions
HA
pH

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8
Q

A ___ ___ is a proton acceptor. It exists in plasma as neutral and cation forms in equilibrium. Bases are ____ in their nonprotonated form and ____ when protonated. ____ does not cross the membrane in a low ____ environment. They are not readily absorbed in the stomach. Bases are readily absorbed in ____ environments.

A

Weak base
Neutral
Charges
Cation
pH
Basic

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9
Q

Many drugs are weak ___ and not weak ___. We can increase the ____ of the stomach.

A

Weak acids
Weak bases
pH

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10
Q

____ ___ is the ability to trap compounds on one side of the membrane or another if there is a pH gradient. Ex: weak acid drug with calcium carbonate like Tums would trap the weak acid in the form that we want it

A

Ion trapping

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11
Q

Weak acids are trapped in ___ environments. Weak bases are trapped I. ____ environments.

A

Basic
Acidic

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12
Q
A
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13
Q

____ ____ is a drug that is not bound by proteins. Only this drug has pharmacokinetic activity and can cross a membrane

A

Free

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14
Q

_____ ____ is a drug passively moving down their concentration gradient across a lipid bilayer

A

Simple diffusion

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15
Q

_____ ____ is when molecules move down their concentration gradient but with the help of channel protein or carrier protein

A

Passive transport

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16
Q

____ ____ moves molecules against the concentration gradient and needs energy

A

Active

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17
Q

Summary of transport mechanisms :

A
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18
Q

A lot of transport proteins are _____ meaning they are expressed on one side of the cell or the other

A

Polarized

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19
Q

______ ______ are slight differences, such as a single nucleotide variant, that changes how a protein transporter works

A

Interindividual variability

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20
Q

______ is the study of how genes affect the response to medications

A

Pharmacogenomics (PGx)

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21
Q

We can use a patients _____ to optimize drug dosing. This is called _____ medicine.

A

Genetics
Precision

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22
Q

Active _____ transport is keeping drug molecules out of a compartment. Active _____ transport is maintaining a higher concentration of drug inside a compartment

A

Efflux
Influx

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23
Q
A
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24
Q

Routes of administration:
Enteral/oral: absorbed ____ the intestines
Parenteral: absorbed ____ the intestines

A

Inside
Outside

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25
Absorption efficiency: _____ is the fastest, then _____, then ____, and the slowest is____
Intravenous IM Subcutaneous Oral
26
_____ describes how efficient or inefficiently a drug is absorbed based on different routes
Bioavailability
27
The most common route is ____.
Orally
28
Oral drugs have to pass through the GI tract and make it into the target area. ____ ____ ____ metabolism.
First pass hepatic
29
Bioavailability (f) is how much drug makes it into the circulating ____. This is oral absorption. It is expressed as a fraction. 100% bioavailable = _____ administration. _____ refers to the area under the curve.
Plasma IV AUC
30
_____ avoids the first pass metabolism because it is absorbed directly into the blood stream through the mouth. ____ also avoids the first pass metabolism.
Sublingual Rectal
31
The ____ is usually the most important contributor to first pass metabolism
Liver
32
After the drug has made it into plasma circulation it needs to be ____. This process is effected by tissue perfusion rates, plasma protein binding, and partitioning between plasma and tissue
Distributed (Kidney and liver have high perfusion) (Plasma protein binding inhibits distribution) (Where does the drug like to partition)
33
Free drug and drug bound to protein is circulating in the plasma, only ____ ___ will be able to make it to the site of action, to other reservoirs, and to a site where it can be metabolized
Free drug
34
____ ___ is how much blood flow is given to a specific tissue. Kidneys lung liver and brain all have high perfusion. The drug will be distributed there ____.
Perfusion rate Faster
35
Bound drugs are ____ ____. Best known plasma proteins are ____ and _____. They both bind to many weak acids
Pharmacologically inert Albumin Alpha 1 acid glycoprotein (AGP)
36
____ ____ refers to the concentration of a drug between plasma and tissue is often not equal. Sometimes drugs prefer to bind to tissue rather than plasma
Plasma partitioning
37
The ____ ____ ____ is a very “tight”endothelium in the capillary bed and glial cells. Only certain drugs can make it passed.
Blood brain Barrier
38
The volume of distribution: simple container model
39
Highly ____ ____ drugs distribute far more widely into tissue and have a large VD
Lipid soluble
40
____ determines the distribution of drugs between the blood and the rest of the body.
Vd
41
This is a low Vd
42
This is a very high Vd
43
Drugs with a high Vd have a ____ initial concentration in the blood. Drugs with a low Vd have a ____ initial concentration in the blood.
Low High
44
A ______ drug will have a smaller Vd and maybe only distribute into the plasma or ECF
Hydrophilic
45
______ volume of distribution is the total amount in the body divided by the total concentration in a measured reference compartment
Apparent
46
Example
500L is not a real volume, plasma is only 42 liters
47
Vd reflect the relative affinity of a drug for the whole ____ and ____. It essentially represents the body as a big bag of plasma into which drugs are diluted. The Vd is the volume of ____ that would be required to contain all of the drug in the body given the measured concentration in only the plasma
Body Plasma Plasma
48
The Vd is often normalized to ___ ___ as the ratio of different tissue types can vary from individual to individual
Body weight
49
50
True or false: If a drug is bound to the plasma proteins, then the drug will have a large Vd
False
51
____ of drug action is accomplished by metabolism (bio transformation) and excretion/elimination
Termination
52
____ is the chemical modification of compounds to make them more polar, more readily eliminated
Biotransformation
53
Bio transformation usually changes the shape of the drug, making them either ____ or ____. A ___ drug is a drug that is designed to be metabolized and transformed into their active form. Ex: Codeine
Active Inactive Pro
54
The ____ is the main site of metabolism. Optimized space and surface area using a hexagon structure
Liver
55
Bio transformation phase 1 and phase 2 both add _____ groups to make drugs more dissolvable, therefore more polar
Functional
56
Phase 1 bio transformation usually introduces the ____ group making the drug functional. Phase 2 typically _____ the functional group added in phase 1
Functional Attacks
57
Not all drugs undergo phase ___ of biotransformation
1
58
59
____ is the most common type of reaction in phase 1. Metabolites are often ____ chemically reactive after phase 1
Oxidation More
60
____ is the most common type of reaction in phase 1. Metabolites are often ____ chemically reactive after phase 1
Oxidation More
61
______ enzyme family is by far the biggest contributors to phase 1 metabolism. About 75% of known drugs are metabolized by these enzymes. They are localized to the ____ _____ ___ in the cell
Cytochrome P450 Smooth Endoplasmic reticulum
62
CYP450s are easily ____, meaning the cell has the ability to make more of this enzyme. Ex: St. John’s wart is an herb that upregulates cyp450 in the body which has effects on other drugs
Induced
63
_____ is also a big inducer of CYP2E1 which effects the metabolism of acetaminophen to go down a route that has a toxic byproduct
Ethanol (alcohol)
64
_____ induces CYP1A2, which effects the metabolism of antidepressants and antipsychotics
Smoking
65
Grapefruit juice ____ cytochrome P450 enzymes. Ex: statins, it takes a lot more time to metabolism
Inhibits
66
It is also very common to have ___ ___ interactions, prescriptions must be managed carefully
Drug-drug
67
An enzyme inducer will increase the clearance by providing more enzyme, drug concentration in the body will ____. An enzyme inhibitor will decrease the amount of enzyme, drug concentration will ____.
Decrease Increase
68
______ has caused a lot of different outcomes due to genetic variability
CYP2D6
69
Very different outcomes in ____ cancer treatment depending on if people are extensive metabolizers of CYP2D6 or poor metabolizers
Breast
70
Phase 2 are usually _____ reactions such as acetylation, sulfate conjugation, methylation, glutathione conjugation. The result is usually _____
Conjugation Inactivation
71
Phase II drug metabolism enzymes:
72
Phase 1 and phase II metabolism summary:
73
74
The ____ is the major site of drug excretion. Primary function is to remove excess water-soluble molecules from the ____ and return water to the central system
Kidney Blood
75
Three modes of excretion in kidney: 1. _____ - portion of blood flow to the kidneys is filtered through glomerular capillaries to remove compounds 2. ____ - create concentration gradient in collecting tubule and compound diffuses back out 3. _____ - active transporters along the tubule selectively pull compounds from plasma and dump into the urine
Filtration Reabsorption Secretion
76
____ ____ is the volume of plasma that is cleared of a drug by the kidney per minute. It is based on glomerular filtration rate of kidneys. This goes down as you age
Renal clearance (CIR)
77
When a solute is freely filtered (not reabsorbed or decreased) then glomerular filtration rate equals the ____ ____
Renal clearance
78
Excretion of drug equation:
79
If only _____ is occurring in the kidney, CIR = GFR.
Filtration
80
_____ measures the health of the kidney
Creatinine
81
If kidneys are filtering and reabsorbing the drug back into the blood stream, CIR is ____ than GFR. This is the case of Mandy drugs
Less
82
If the drug is filtered and secreted by the kidney, the CIR is ____ than the GFR. An example of this is p-aminohippurate (PAH)
Greater
83
Review:
84
Plasma concentration = _____ / _____. As clearance increases, the plasma concentration ____ because the drug is more readily metabolized and excreted
Dose rate Clearance Decreases
85
86
Y axis: ____ ___ X axis: ____ MTC: ____ ____ ____ MEC: ____ ____ ___ The ____ ____ is between the above two things
Drug concentration Time Minimum toxic concentration Minimum effective concentration Therapeutic range
87
____ ___: when the patient first reaches the beginning of the therapeutic range
Onset time
88
Tmax is the time at which the maximum drug _____ is reached
Concentration
89
Cmax is the max ____ of the drug
Concentration
90
____ = plasma concentration x Vd
Dose
91
The units of dose should be ___
mg
92
____ = total drug dose / plasma concentration
Vd
93
___ is the elimination rate constant
k
94
k = ____ / ____ Units for k: ___
Clearance / Vd 1/hr
95
t half life = _____ / ____ t half life = _____ ____ / ____
0.693 / k (0.693)(Vd) / clearance
96
If the Vd increases, the half life ____
Increases
97
If clearance increases than half life ____
Decreases
98
First order kinetics is ____ kinetics and most easily visualized on a semi-log plot
Linear
99
C0 is the concentration of the drug as soon as it is ___
Administered
100
Log plot of first order kinetics drugs:
101
Zero order kinetics
102
___ ___ kinetics is when the elimination rate changes proportionally to the does
First order
103
___ ___ is when the elimination rate remains constant independently of the dose
Zero order
104
Maintenance dose = (_____) ( ____) / ____
(IV dosing rate) (desired oral dose interval) / F
105
Equations to memorize:

Fundamentals of Medicine: Exam II (19 decks)

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