Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

z Biopharm > Absorption to Distribution > Flashcards

Absorption to Distribution Flashcards

1
Q

The fraction of dose absorbed (BIOAVAILABILITY) is calculated by:

A

Amount of drug in blood over time (area under PK curve)/ dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

(True/False) The relative bioavailability can be calculated by Fa/Fiv, while the absolute bioavailability can be calculated by Fa/Fb.

A

False! The relative bioavailability can be calculated by Fa/Fb, while the absolute bioavailability can be calculated by Fa/Fiv.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sophie, a 29-year old with a viral infection, is given an 100 mg IV dose of Vironiblast and responds well but requires more treatment.

Sophie bruises easily so is switched to an oral dose. Based on Vironiblast’s oral bioavailability (F = 0.40), what dose (how much drug) will Sophie receive?

A

F = AUC/dose
Dose = AUC/F = 100mg/0.40 = 240mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

(T/F) The absorption of most xenobiotics is via active transport and follows first order kinetics.

A

False, The absorption of most xenobiotics is via DIFFUSION and follows first order kinetics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Match the following terms with their definition:

  1. U
  2. [S]
  3. Vmax
  4. Ka
  5. Ke

A. substance concentration at site of absorption
B. absorption rate
C. elimination rate constant
D. maximum rate achieved at saturating substance concentrations
E. substrate concentration at which the absorption rate is half of Vmax (absorption rate constant)

A

U = absorption rate
[S] = substance concentration at site of absorption
Vmax = maximum rate achieved at saturating substance concentrations
Ka = substrate concentration at which the absorption rate is half of Vmax (absorption rate constant)
Ke = elimination rate constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The slower the elimination (small __), the better the ________.

A

Ke
Bioavailability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

In first order kinetics, a constant ________ of substance is absorbed per time. The reaction rate is ________ to [S].

In zero order kinetics, a constant ______ of substance is absorbed per time. The reaction rate is CONSTANT and ______ of [S].

A

fraction; proportional

amount; independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

(T/F) Unsaturated facilitated proteins use zero order kinetics.

A

False! Unsaturated facilitated proteins use FIRST order kinetics until saturated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

(T/F) Usually for 1st order kinetics, [S] &laquo_space;k (reaction rate) and for 0 order kinetics, with large doses, [S]&raquo_space; k.

A

True!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the five ways Ka (absorption rate constant) for a given drug can change?

A
  1. Changing the formulation
  2. Changing the dosage form or the extravascular route of administration
  3. Administration of drug with or without food
  4. Health of organism
  5. Presence of other substances (competition/inhibition)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When absorption rate is greater than elimination rate, there is ______ absorption, _______ onset of action and a ______ Cmax.

A

quicker
faster
greater

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is distribution?

A

How substances move through the blood stream and how they reversibly leave the bloodstream into the interstitium then cells of other tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the five physical factors that influence distribution?

A
  1. Substance properties - depot + fluid
  2. Matrix properties
  3. Route of exposure/administration
  4. Biological barriers
  5. Blood supply to absorption sites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the two main reasons that greater blood flow in absorption site results in greater distribution?

A
  1. Maintains concentration gradients
  2. Gets to heart more quickly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

(T/F) Concentration of drug at site of exposure is constant.

A

True!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does the local concentration of a drug change with time?

A
  1. Nature of exposure
  2. Degree of perfusion
  3. Formulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does the concentration of a drug in systemic circulation change with time?

A
  1. Metabolism
  2. Storage
  3. Elimination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

(T/F) Highest drug concentration is always at the site of absorption.

A

True!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are two transports that take a drug from absorption to distribution (local sites to systemic circulation)? Briefly describe them.

A
  1. Transcellular transport - through capillary endothelial cell membrane. For lipophilic drugs through diffusion.
  2. Paracellular transport - through extracellular fluid (interstitial into blood or lymph) between endothelial cells. For hydrophilic drugs that can’t enter cell membranes.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the interstitial fluid? What is it chemically and ionically similar to?

A

The fluid surrounding the cells that permits the exchange of materials. LYMPH is a form of interstitial fluid collected and transported by the lymph system. It is chemically similar to plasma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The primary mechanism for topical xenobiotics is _________, which is also a primary mean of interstitial transport.

A

DIFFUSION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the four means of paracellular transport?

A
  1. Tight junctions
  2. Fenestrations
  3. Intercellular clefts
  4. Intercellular gaps
23
Q

Match the different types of capillaries to their definitions:

  1. Continuous
  2. Fenestrated
  3. Discontinuous

a. larger junctions and discontinuities. Highly permeable to PLASMA proteins. In organs where RBC and WBC need to MIGRATE BETWEEN BLOOD AND TISSUE - bone marrow & liver
b. continuous ring of ENDOTHELIAL cells surrounded by a continuous membrane. Found in MOST TISSUES.
c. highly permeable to water and solutes. TISSUES THAT SPECIALIZE IN FLUID EXCHANGE - kidneys, exocrine glands, choroid plexus.

A

Continuous - continuous ring of ENDOTHELIAL cells surrounded by a continuous membrane. Found in MOST TISSUES.

Fenestrated - highly permeable to water and solutes. TISSUES THAT SPECIALIZE IN FLUID EXCHANGE - kidneys, exocrine glands, choroid plexus.

Discontinuous - larger junctions and discontinuities. Highly permeable to PLASMA PROTEINS. In organs where RBC and WBC need to MIGRATE BETWEEN BLOOD AND TISSUE - bone marrow & liver (proteins cross membranes)

24
Q

What is the initial barrier of distribution?

A

Getting into the blood.

25
Q

Once the substance is in the blood, it circulates throughout the body. It is driven by _____ _____ and _____ _____. It is bound or unbound to ______ proteins and is limited by biological ______.

A

Blood pressure; cardiac output

Plasma

Barriers

26
Q

Rate of blood flow to tissue capillaries varies widely. Match the following terms to their definitions:

  1. Central
  2. Middle
  3. Peripheral

A. gets medium amount of blood, composed of SKELETAL MUSCLE, EYE.
B. gets the lowest amount of blood because the organs are not being used actively. SKIN, TENDONS, FAT and BONE.
C. gets the MOST blood. composed of BRAIN, LIVER, HEART, KIDNEY

A
  1. Central - gets the MOST blood. composed of BRAIN, LIVER, HEART, KIDNEY
  2. Middle - gets medium amount of blood, composed of SKELETAL MUSCLE, EYE.
  3. Peripheral - gets the lowest amount of blood because the organs are not being used actively. SKIN, TENDONS, FAT and BONE.
27
Q

To treat peripheral sites, where there is a very low amount of blood, I would need a higher _____ ______ so it can eventually get there.

A

SYSTEMIC [DRUG]

28
Q

What is redistribution?

A

The movement of a substance from an area of high regional blood flow to an area of medium or low regional blood flow.

For example, when a drug goes from the blood to the brain (one of the organs with the highest blood flow), there is a lower concentration in the blood and higher in the brain. This causes the drug to leave the brain and go to an area of medium blood flow (muscles). When the drug concentration is higher there, it leaves that area and goes to a lower regional blood flow (fat tissues). Lipophilic molecules tend to stay in fatty acids.

The drugs that are distributed to the brain, heart, kidney, etc are immediately followed by muscle and fats.

29
Q

Even though distribution occurs in some extent in all drugs, which ones are most affected by it?

A

Lipophilic CNS acting drugs!

It accounts for the extremely rapid onset and short duration of these drugs. Like THIOPENTAL.

30
Q

Most xenobiotics bind reversibly and nonspecifically to plasma proteins (PLASMA PROTEIN BINDING), and their extent of binding depends on compound’s ______ _____ for the protein. Increasing concentrations _______ binding sites.

There is an ___________ between free and bound fractions.

Bound drug is _______ and _______ to biological barriers.

Unbound drug can act at target sites in tissues and are available for _________ and ________.

A

Physiological affinity; Saturate

Equilibrium

Inactive; Impermeable (can’t be eliminated)

Metabolism; Elimination

31
Q

What are the five different types of plasma proteins that drugs can bind to?

A
  1. Albumin
  2. Lipoproteins
  3. Glycoproteins
  4. Nucleic acids
  5. B-globulins
32
Q

Weak acid xenobiotics bind most often to ________, while weak base xenobiotics bind most often to ______________.

A

Albumin

α-1 acid glycoprotein

33
Q

(T/F) While the free form of a xenobiotic is free to leave circulation, bound form is restricted to vascular compartment and acts as a STORAGE depot.

A

True!

34
Q

(T/F) For highly bound xenobiotics (like Naproxen), small proportion is not continuously freed as unbound molecules leave circulation.

A

False! It is continuously freed as the unbound leaves the circulation and the equilibrium readjusts, slowing elimination.

35
Q

For high plasma protein binding, there is a _____ free drug concentration and a _____ clearance which results in ______ total drug concentration.

A

lower, low, higher

Overall, there is a long duration of action with mild effects.

36
Q

For low plasma protein binding, there is a _____ free drug concentration and a _____ clearance which results in ______ total drug concentration.

A

higher, high, lower

Overall, there is a short duration of action with high effects.

37
Q

Where is albumin synthesized? What is its half life? What are two of its resposibilities?

A

Liver
17-18 days
1. Maintain osmotic pressure of blood
2. Transport of endogenous and exogenous substances

38
Q

(T/F) Through electrostatic and hydrophobic bonds, albumin complexes with free fatty acids, hormones, weakly acidic and hydrophobic xenobiotics.

A

True!

39
Q

What is a high capacity albumin molecule vs a low capacity albumin molecule?

A

High capacity = several xenobiotic molecules per albumin
Low capacity = one xenobiotic molecule per albumin

40
Q

(T/F) Albumin has strongest affinity for neutral and hydrophilic molecules.

A

False, it has the strongest affinity for neutral and lipophilic molecules.

41
Q

Match the following terms to their definitions:

  1. Class 1 substances
  2. Class 2 substances

a) high dose/capacity ratio. Dose is greater than available binding sites. Most albumin molecules bound to a drug and the [free drug] is high. Mechanism of drug-drug interaction.
b) low dose/capacity ratio. Dose is less than available binding sites. Most drugs are bound and the [free drug] is low. No competition or displacement. Most drugs.

A

Class 1 substances = low dose/capacity ratio. Dose is less than available binding sites. Most drugs are bound and the [free drug] is low. No competition or displacement. Most drugs.

Class 2 substrates = high dose/capacity ratio. Dose is greater than available binding sites. Most albumin molecules bound to a drug and the [free drug] is high. Mechanism of drug-drug interaction.

42
Q

What is a drug-drug interaction?

A

If a patient is taking both class 1 and class 2 drugs, the class 2 drug can displace class 1 drug. More of class 1 drug is free than usual, increasing its pharmacodynamics. This causes side effects and high elimination rate.

43
Q

In addition to PPB depot, xenobiotics can accumulate in tissues. Match the sites of accumulation with the xenobiotics.

  1. Adipose tissue
  2. Bones and teeth
  3. Heart and skeletal muscle
  4. Thyroid gland
  5. Retina
  6. Liver and Kidneys

A. calcium-binding compounds
B. bound to melanin (non-targeted site of action)
C. iodine-containing compounds
D. toxins (high blood flow + detox function)
E. bound to tissue-specific protein (targeted site of action)
F. lipophilic compounds

A

Adipose tissue - lipophilic compounds
Bones and teeth - calcium-binding compounds
Heart and skeletal muscle - bound to tissue-specific protein (targeted site of action)
Thyroid gland - iodine-containing compounds
Retina - bound to melanin (non-targeted site of action)
Liver and Kidneys - toxins (high blood flow + detox function)

44
Q

(T/F) Getting out of the blood is the same as getting into the blood. Gases and lipid soluble molecules easy, while water soluble compounds may need to undergo paracellular pathways.

A

True!

45
Q

Which molecules does blood-brain barrier allow permeation of? and through which kind of transport?

A

1) Gases (passive)
2) Nutrients (active + passive)
3) Hormones (active)
4) Small, lipid soluble, unionized compounds (passive)
5) “mimics” (active)

46
Q

(T/F) There is more fenestrations, intercellular clefts and less tight junctions in the brain capillary than a typical capillary.

A

False, there is less fenestrations, intercellular clefts and more tight junctions in the brain capillary than a typical capillary.

47
Q

What are P-glycoproteins? What do they do? Where are they found?

A

ATP-driven EFFLUX pumps (ABC transporters).

Transport nutrients, xenobiotics + others out of cell cytoplasm. Oppose absorption + distribution of drugs and favour elimination. DETOXIFICATION MECHANISM.

Found in intestines, brain, kidneys, gonads, liver, pancreas, etc.

48
Q

(T/F) Blood-placenta barrier and BBB allow permeation of the same molecules are the same level of permeability.

A

False! BBB less permeable but they do allow the permeation of same molecules.

49
Q

What is the volume of distribution?

A

Vd = amount absorbed into body (dose)/[plasma]

*where the plasma levels are measured after intravenous exposure which often deviate from expected values; APPARENT VOD

*a constant

50
Q

What are the five main barriers that xenobiotics must permeate to get out of the bloodstream and into different organs + tissues?

A
  1. Capillary wall (to reach anywhere)
  2. Blood-brain barrier (most well protected)
  3. Blood-cerebrospinal barrier
  4. Blood-retinal barrier
  5. Blood-placenta barrier
51
Q

Match the following terms with its definition regarding VOD:
1) Low Vd (<9 L)
2) High Vd (>40 L)
3) Medium Vd (9-40L)

A

Low Vd (<9 L) - drug likes to stay in plasma
High Vd (>40L) - drug likes to leave blood and stay in extravascular compartments
Medium Vd (9-40L) - if its around 40, most drug is outside of plasma and if tis around 9, most drug is in plasma.

52
Q

(T/F) 1/3 of our total body water (42L) is intracellular fluid while 2/3 is extracellular fluid.

A

False! 1/3 is extracellular and 2/3 is intracellular!

53
Q

Predict how the following substance properties will affect Vd + provide a brief explanation as why:
1) Big molecule
2) Small molecule
3) High plasma protein binding
4) Weak plasma protein binding
5) Hydrophilic
6) Lipophilic
7) Charged
8) Neutral

A

1) Big molecule - harder to leave blood; low Vd
2) Small molecule - easier to leave blood; high Vd
3) High plasma protein binding; harder to leave blood; low Vd
4) Weak plasma protein binding; easier to leave blood; high Vd
5) Hydrophilic; harder to cross cell membrane; stuck in blood; low Vd
6) Lipophilic; easier to cross cell membrane; high Vd
7) Charged; harder to cross cell membrane; stuck in blood; low Vd
8) Neutral; easier to cross cell membrane; high Vd

54
Q

Why do we depend on plasma concentration even though most drug don’t act within the blood for apparent VOD?

A

Assume plasma concentration is proportional to target tissue concentration.

z Biopharm (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions