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MPharm 2 - PH2114 > Unit 2 - Biological barriers & ADME 2 > Flashcards

Unit 2 - Biological barriers & ADME 2 Flashcards

1
Q

What is the approximate volume of total body fluid?

A

42 litres

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2
Q

What is the approximate volume of intracellular fluid?

A

28 litres

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3
Q

What is the approximate volume of extracellular fluid?

A

14 litres

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4
Q

What is the approximate volume of interstitial fluid?

A

10 litres

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5
Q

What is the approximate volume of plasma?

A

5 litres

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6
Q

what are the categories body fluids are distributed into ?

A

body is 60% fluid

intracellular fluid - 40% body weight

Extracellular fluid - 20% body weight
(Plasma & interstitial fluid)

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7
Q

How can drug sequestration take place?

A 
Lipid sequestration
- drug in plasm
Binding to a host of tissue components
- plasma proteins
- tissue proteins
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8
Q

What percentage of the blood is plasma?

A

55%

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9
Q

What percentage of the blood is red blood cells?

A

45%

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10
Q

What percentage of the blood is white blood cells and platelets?

A

1%

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11
Q

What are the major drug-binding plasma proteins?

A

Plasma is protein rich

Albumin
Alpha1-acid glycoprotein
Lipoproteins
- variable

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12
Q

What is able to cross cellular barriers to access tissues, intracellular targets and bind to receptors?

A

Unbound drug

- free drug

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13
Q

What does drug binding have an effect on?

A

Distribution and Elimination of drug

Pharmacologic response

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14
Q

What is Fu?

A

Fraction of total mass of drug in plasma (blood) that is unbound

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15
Q

How can fraction unbound be calculated?

A

Fu = drug concentration [free] / drug concentration plasma [total]

[Total] = free + bound

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16
Q

Describe the concept of reversible equilibrium

A

Drug enters the plasma

Equilibrium between free drug in plasma and bound drug in plasma
Equilibrium between free drug in plasma and free drug in tissue compartment
Equilibrium between free drug in tissue and bound drug in tissue

17
Q

How much albumin is produced a day by hepatocytes?

A

9 - 12g/day

18
Q

What is the concentration of albumin in plasma?

A

40 g/L

19
Q

How many binding sites does albumin have?

A

Two

20
Q

Which type of molecules bind to albumin in plasma?

A

Hydrophobic

Negative charge or electronegative feature

21
Q

How can the affinity for a drug to albumin be increased?

A 
More acidic (pKa < 6)
More hydrophobic
22
Q

What is alpha1-acid glycoprotein?

A

Heavily glycosylated plasma protein synthesised in the liver

23
Q

How many binding sites does alpha 1-acid glycoprotein have?

A

One

24
Q

Which type of molecules bind to alpha 1-acid glycoprotein in plasma?

A

Hydrophobic

Positive charge or electropositive feature

25
Q

Give examples of plasma lipoproteins

A

Triglycerides and cholesterol esters
Phospholipids
Cholesterol
Proteins

26
Q

Give examples of plasma lipoprotein particles

A 
High-density lipoprotein
- HDL
Low-density lipoprotein
- LDL
Intermediate density lipoprotein
- IDL
Very low density lipoprotein
- VLDL
Chylomicrons
- CM
27
Q

What is the function of plasma lipoproteins?

A

To transport various fat molecules around body to tissues

28
Q

How do plasma lipoproteins sequest drugs?

A 
Lipid solubilisation of drug into core
Lipid interaction with surface phospholipids
- non-restrictive
- non-saturable
Binding to surface apoproteins
29
Q

What is the structure of a plasma lipoprotein?

A 
Surface monolayer
- phospholipids
- free cholesterol
- protein
Hydrophobic core
- triglyceride
- cholesteryl esters
30
Q

What might cause albumin levels to decrease?

A 
Burns
Liver damage
- synthesises albumin
Renal disease
- eliminates albumin
Malnutrition
- can't synthesise albumin
31
Q

What might cause alpha 1-acid glycoprotein levels to increase?

A 
Inflammatory disease
- rheumatic arthritis
- Crohn's disease
Cancer
Trauma
32
Q

What might cause alpha 1-acid glycoprotein levels to decrease?

A

Liver disease

- synthesises alpha1-acid glycoprotein

MPharm 2 - PH2114 (32 decks)

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