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BIOM20002 - HSF > Lecture 34 - Pharmacokinetics 1 > Flashcards

Lecture 34 - Pharmacokinetics 1 Flashcards

1
Q

What are the principles of Pharmacokinetics?

A

A: absorption
D: distribution
M: metabolism
E: excretion

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2
Q

What are the different routes of delivery?

A 
Oral
Sublingual
Intramuscular
Intravenous
Transdermal
Suppository
Inhalational
Topical
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3
Q

Which route of delivery gives the fastest delivery into the blood?
What about other routes?

A

I/ Intravenous
II/ Intravenous
III/ Subcutaneous
IV/ Oral

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4
Q

What are the barriers to permeation?

A

Epithelial linings
Tight junctions
Lipid cell membrane

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5
Q

What is the structure of a villous?

A

Enterocytes with microvilli
Rich blood supply, capillaries
High SA:V ratio

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6
Q

Relate the structure to the function of villi

A

Great SA: for absorption
Capillaries: keeps a constant concentration gradient
Mitochondria: energy for active transport into the cells
Thin intima
Many transporters

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7
Q

How can substances cross the epithelium?

A

Around cells:
- Paracellular

Through cells:

  • Transcellular, diffusion
  • Transporter
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8
Q

How can substances cross the cell membrane?

A

1 - Diffusion
2 - Through a pore (Aqueous diffusion)
3 - Carrier: active / facilitated
4 - Pinocytosis

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9
Q

Which drugs can get into cells the most readily?

A

Lipid soluble drugs

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10
Q

Lipid solubility is dependent on:

A
  • Intrinsic structure

- pH of conditions

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11
Q

Describe compartment trapping of Aspirin

A
  1. Aspirin is a weak acid
  2. In stomach, it is protonated, neutral
  3. Diffuses across cells into blood
  4. Blood pH is 7.4
  5. Aspirin is ionised in the blood
  6. Can no longer diffuse through cells
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12
Q

What is ‘distribution’ of drugs?

A

Which organs and tissues the drug goes to from the blood

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13
Q

What is ‘absorption’ of drugs?

A

How the drug gets into the body

How it gets across cell membranes

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14
Q

What is the difference between normal and fenestrated capillaries?

A

Normal: continuous

Fenestrated: holes, through which material can move

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15
Q

Capillaries of which organs are fenestrated?

A

Liver, hepatic sinusoids
Kidney
Intestines

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16
Q

When is pericellular passage possible?

A

When the capillaries are loose

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17
Q

Describe the capillaries in the brain

A

Very tight junctions

Nothing can move between cells (pericellular)

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18
Q

How can a substance get into the brain?

A
  • Be lipid soluble, small, uncharged

- Have a transporter

19
Q

Why are some antihistamines drowsy, and some not?

A

Old type: lipid soluble, gets into the brain, activates drowsiness centre

New type: (fexofenadine): not lipid soluble, can’t get across blood brain barrier

20
Q

Which types of organs are readily accessible to drugs?

A

Organs with fenestrated capillaries

21
Q

Describe blood flow to different organs

A

Different organs get different blood flow

High: brain, kidney, liver, heart

Low: Fat, muscle

22
Q

What is blood-flow dependent distribution?

A

Delivery depends on different things, depending on whether the organ receives a lot of blood

Low flow: delivery depends on flow and drug concentration

High flow: delivery depends on flow

23
Q

What is thiopental?

A

An anaesthetic

24
Q

What are the features of thiopental?

A

Lipid soluble

25
Q

How is thiopental administered?

A

Intravenous injection

26
Q

When in the peak concentration of thiopental in the brain?

A

10 minutes after injection

27
Q

When does thiopental peak in muscle?

A

20 minutes

28
Q

When does thiopental peak in fat?

A

6 hours

29
Q

Describe the delivery of thiopental to different organs in the body

A

Initially: goes to brain, then is ejected out after 10 mins

Then: goes to muscle

Later: slowly builds up in fat

30
Q

Why does thiopental build up in lipid?

Why does it take a long time for thiopental to go here?

A

Thiopental has an affinity for lipid

It takes a while to build up here because there is poor blood flow to fat

31
Q

What determines the drug’s stability in the body?

A

Whether or not it binds to a protein

32
Q

Give an example of a drug binding to a protein in the blood

A

Thyroxine binds to a globulin (TBG)

Prevents thyroxine from being filtered out by the kidney

33
Q

What does protein binding of drugs affect?

A

Distribution

Clearance

34
Q

Why does thyroxine only have to be taken once a week?

A

Because it binds to Thyroxine Binding Protein –> it now has a longer half life

35
Q

What is the function of Albumin?

A

Generic drug binding protein

36
Q

Where is the vast amount of drug metabolism performed?

What is this called

A

First Pass Metabolism

In the liver

37
Q

“All roads lead to Rome”

What is rome in this metaphor?

A

The liver is rome

Blood from the gut goes directly to the liver

38
Q

Which routes of delivery avoid first pass metabolism?

A

Sublingual

Inhalational

39
Q

Can drugs be absorbed in the mouth?

A

Some can

Under the tongue, where the epithelium is thin and there is much blood flow

40
Q

Can drugs be absorbed in the eosophagus?

A

No

41
Q

Can drugs be absorbed in the stomach?

A

No, it has protective mucous to prevent acid damage

42
Q

Why is the Henderson-Hasselbach equation important?

A

Drugs may be charged or uncharged in certain pHs

43
Q

When are weak acids charged?

When are weak bases charged?

A

Weak acids: in basic solution

Weak bases: in acidic solution

BIOM20002 - HSF (60 decks)

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