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PM2B Spring Amy L > Pharmacokinetics Biopharmaceutics (2/3) > Flashcards

Pharmacokinetics Biopharmaceutics (2/3) Flashcards

1
Q

List the 3 possible sites of absorption

A

Stomach
Small intestine
Large intestine

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2
Q

How long is a dosage form’s residence time in the stomach?

A

Minutes to hours, depending on food

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3
Q

List 4 factors that affect gastric residence time

A

Type of dosage form (solid/liquid)
Presence of food (delays emptying)
Posture
Effect of other drugs on gastric motility

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4
Q

Name the 3 parts of the small intestine

A 
Duodenum (shortest)
Jejenum
Ileum (longest)
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5
Q

What is the pH range of the small intestine?

A

pH 5-7

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6
Q

Which 3 structural features of the small intestine increases its SA to 200m2?

A

Folds
Villi
Microvilli

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7
Q

What is the pH range and residence time of the large intestine?

A

pH 5-7

Residence time = hours

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8
Q

List the 3 main mechanisms of absorption and 1 additional process

A

Passive transport (diffusion)
Facilitated transport
Active transport

Endocytosis

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9
Q

Describe the process of passive diffusion

A

API moves from region of high API concentration (GIT side) to region of low API concentration (blood side)
Water-soluble API = aqueous channel or pore
Lipid-soluble API = dissolved in membrane
Most APIs cross GIT membranes by this mechanism

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10
Q

What does Fick’s 1st Law indicate?

A

The rate of diffusion of an API across the membrane

Where dC/dh is a constant

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11
Q

Define: Fick’s 1st Law

A

picture 1

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12
Q

Define the terms of Fick’s 1st Law

A 
J = The flux (the amount of material per unit area per unit time) of the API passing across a membrane 
D = the diffusion coefficient of the API
C(GIT) = the API concentration on the GIT side
C(Blood) = the API concentration on the blood side of the membrane
h = the thickness of the membrane
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13
Q

How is the concentration of API on the blood side kept low?

A

The blood carries away the API into circulation

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14
Q

Describe facilitated diffusion

A

API is helped across the membrane by carrier molecules
This process does not require energy
Concentration driven

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15
Q

Describe active transport

A

Helped across the membrane by carrier molecules
BUT does require energy input
Capable of moving APIs against the concentration gradient

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16
Q

Describe the relevance of endocytosis to the transport of APIs

A

API brought into the cell via endocytosis (vesicle formed from cell membrane)
Not applicable to small APIs
Relevant for some much larger therapeutic agents

17
Q

What 2 properties must APIs have in order to be well absorbed and so have good bioavailability? Why?

A

Some element of water solubility and some element of fat solubility
This is because API must be in solution to be absorbed from the GIT and must pass across fatty GIT membranes

18
Q

List 3 key physiochemical factors

A

Solubility
pKa
Log P

19
Q

What does the partition coefficent (P) measure?

A

Measures partitioning of API between an octanol phase (‘fatty’) and an aqueous phase

20
Q

What is the partition coefficient equation?

A

2 equations

21
Q

What does a high concentration of the API in the octanol phase mean?

A

Very hydrophobic

22
Q

What does a high P value of an API suggest?

A

Very hydrophobic

Low P means very hydrophilic

23
Q

What does a negative logP value suggest about an API?

A

The API is very hydrophilic

24
Q

What does a positive log P value suggest about an API?

A

The API is very hydrophobic

25
Q

What does the acid dissociation constant (Ka) measure?

A

Ka measures the extent to which an acid dissociates in solution

26
Q

What are the 2 equations that involve the acid dissociation constant

A

2

27
Q

What does a large pKa indicate?

A

A weaker acid

28
Q

What does a large Ka indicate?

A

A stronger acid

29
Q

What does a small pKa indicate?

A

A stronger acid

30
Q

What does a small Ka indicate?

A

A weaker acid

31
Q

What does a high concentration of [H+][A-] suggest?

A

Stronger acid

32
Q

What does a high concentration of [HA] suggest?

A

Weaker acid

33
Q

What does a high pKa value suggest about a base?

A

A stronger base

34
Q

What can weak bases accept in an equilibrium reaction?

A

The weak base can accept protons from water in an equilibrium reaction

35
Q

What do pKa values apply to in an API?

A

The individual functional groups of the API

If an API has only 1 ionisable group, then the pKa of the API is that of the ionisable group
If an API has more than 1 ionisable group, each group will have its own API value

36
Q

What is the Henderson-Hasselbach equation used for?

A

Used to calculate the extent of dissociation of an API of given pKa, at any pH

PM2B Spring Amy L (16 decks)

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