Lecture 34 - Pharmacokinetics 1 Flashcards
What are the principles of Pharmacokinetics?
A: absorption
D: distribution
M: metabolism
E: excretion
What are the different routes of delivery?
Oral Sublingual Intramuscular Intravenous Transdermal Suppository Inhalational Topical
Which route of delivery gives the fastest delivery into the blood?
What about other routes?
I/ Intravenous
II/ Intravenous
III/ Subcutaneous
IV/ Oral
What are the barriers to permeation?
Epithelial linings
Tight junctions
Lipid cell membrane
What is the structure of a villous?
Enterocytes with microvilli
Rich blood supply, capillaries
High SA:V ratio
Relate the structure to the function of villi
Great SA: for absorption
Capillaries: keeps a constant concentration gradient
Mitochondria: energy for active transport into the cells
Thin intima
Many transporters
How can substances cross the epithelium?
Around cells:
- Paracellular
Through cells:
- Transcellular, diffusion
- Transporter
How can substances cross the cell membrane?
1 - Diffusion
2 - Through a pore (Aqueous diffusion)
3 - Carrier: active / facilitated
4 - Pinocytosis
Which drugs can get into cells the most readily?
Lipid soluble drugs
Lipid solubility is dependent on:
- Intrinsic structure
- pH of conditions
Describe compartment trapping of Aspirin
- Aspirin is a weak acid
- In stomach, it is protonated, neutral
- Diffuses across cells into blood
- Blood pH is 7.4
- Aspirin is ionised in the blood
- Can no longer diffuse through cells
What is ‘distribution’ of drugs?
Which organs and tissues the drug goes to from the blood
What is ‘absorption’ of drugs?
How the drug gets into the body
How it gets across cell membranes
What is the difference between normal and fenestrated capillaries?
Normal: continuous
Fenestrated: holes, through which material can move
Capillaries of which organs are fenestrated?
Liver, hepatic sinusoids
Kidney
Intestines
When is pericellular passage possible?
When the capillaries are loose
Describe the capillaries in the brain
Very tight junctions
Nothing can move between cells (pericellular)
How can a substance get into the brain?
- Be lipid soluble, small, uncharged
- Have a transporter
Why are some antihistamines drowsy, and some not?
Old type: lipid soluble, gets into the brain, activates drowsiness centre
New type: (fexofenadine): not lipid soluble, can’t get across blood brain barrier
Which types of organs are readily accessible to drugs?
Organs with fenestrated capillaries
Describe blood flow to different organs
Different organs get different blood flow
High: brain, kidney, liver, heart
Low: Fat, muscle
What is blood-flow dependent distribution?
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
What is thiopental?
An anaesthetic
What are the features of thiopental?
Lipid soluble
How is thiopental administered?
Intravenous injection
When in the peak concentration of thiopental in the brain?
10 minutes after injection
When does thiopental peak in muscle?
20 minutes
When does thiopental peak in fat?
6 hours
Describe the delivery of thiopental to different organs in the body
Initially: goes to brain, then is ejected out after 10 mins
Then: goes to muscle
Later: slowly builds up in fat
Why does thiopental build up in lipid?
Why does it take a long time for thiopental to go here?
Thiopental has an affinity for lipid
It takes a while to build up here because there is poor blood flow to fat
What determines the drug’s stability in the body?
Whether or not it binds to a protein
Give an example of a drug binding to a protein in the blood
Thyroxine binds to a globulin (TBG)
Prevents thyroxine from being filtered out by the kidney
What does protein binding of drugs affect?
Distribution
Clearance
Why does thyroxine only have to be taken once a week?
Because it binds to Thyroxine Binding Protein –> it now has a longer half life
What is the function of Albumin?
Generic drug binding protein
Where is the vast amount of drug metabolism performed?
What is this called
First Pass Metabolism
In the liver
“All roads lead to Rome”
What is rome in this metaphor?
The liver is rome
Blood from the gut goes directly to the liver
Which routes of delivery avoid first pass metabolism?
Sublingual
Inhalational
Can drugs be absorbed in the mouth?
Some can
Under the tongue, where the epithelium is thin and there is much blood flow
Can drugs be absorbed in the eosophagus?
No
Can drugs be absorbed in the stomach?
No, it has protective mucous to prevent acid damage
Why is the Henderson-Hasselbach equation important?
Drugs may be charged or uncharged in certain pHs
When are weak acids charged?
When are weak bases charged?
Weak acids: in basic solution
Weak bases: in acidic solution
