Flashcards in Lecture 16: Deck (59):
Why is the route of drug administration important?
Although we know the bioavailability of injections is 100% as it goes straight into the blood stream, not all medications are like this.
Some are degraded on the way, particularly those administered by the oral route
So we need to understand the route of admin to know how much of the drug we should administer to achieve a certain therapeutic level
What is pharmaceutics?
Anything to do with designing dosage forms to develop drugs.
What are two examples of drug delivery designs?
Transdermal drug delivery device
What are the important components of a transdermal drug delivery device?
Reservoir- contains the lactose and drug
Adhesive layer- attaches to the skin
Rate controlling membrane- controls the speed of drug release from the reservoir to the skin
What else do you have to consider when designing a transdermal drug delivery device?
The different layers of the skin.
The device is designed so that the drug is delivered at a controlled rate through the skin, which is then absorbed
What are the vital components of an ocular implant?
Conductive polmers- conduct electricity with drugs loaded within them
Rechargeable port- so patient can go to the doctor to get the implant recharged
What are the advantages of an ocular implant?
It is a really small device which provides medication for AMD
The patient only needs to go once to get the implant, which contains enough information for treatment for 6 months
The rechargeable port enables the patient to visit the doctor to get the implant recharged, when necessary
We are also currently designing a wifi system to enable the doctor to design the dosage
What does pharmaceutics involve? (Traditionally, and now)
Mixing a biologically active entity and additives to make a formulation which is suitable, safe, and effective for the patient
What are the advantages of an oral administration route?
Safe and convenient for patient
Can be used for systemic or local effects
GIT provides large surface area for absorption
What are the disadvantages of the oral administration route?
Drug effect is slow as it requires drug to be in solution phase in order to be absorbed
Some drugs interact with food, can cause adverse effects
Some drugs are sensitive to the low pH environment of the stomach
For drug to have effect it needs to survive acidic conditions as well as enzymatic attack
First pass metabolism is another issue
Drugs may cause unpleasantness, irritation
Oral route is too slow for emergencies,
Cannot be administered to unconscious patients
What is an example of drugs, administered orally, which act locally?
What is an example of a drug that interacts with food?
Tetracycline forms a complex with calcium.
So when taking tetracycline, need to avoid milk as complex formation prevents absorption
What is an example of a drug that is sensitive to the low pH environment of the stomach, and therefore cannot be taken orally?
So it is not given orally in its pure form
What is first pass metabolism?
When the drug is absorbed through the GIT and goes directly to the liver.
some of the active drug is metabolised, resulting in a reduced bioavailability
What is the general anatomy of the GIT?
6m long tract
Most of which is muscular
Includes the oesophagus, stomach and large and small intestines
Irregular structure and folds are mechanisms which increase the surface area for absorption
What is the majority of epithelium of the GIT covered in?
Mucous layer- lubricates GIT, eases passage of food and protects GIT from enzymatic degradation and digestion
What are the advantages and disadvantages of the oesophagus?
+ it has a fast transit time
- if patient has swallowing injury, drug cannot be taken orally
What is the stomach divided into?
Fundus: consisting of acid secreting cells
What substance is all over the stomach?
Mucous, which contains sodium bicarbonate to neutralises HCl to protect stomach tissue.
Is the stomach an absorptive organ?
No it is a digestive organ, and a reservoir which jolds food.
How does the stomach work?
Depending on the nature of the food we take, it releases or moves food in a controlled manner to the duodenum via a controlled sphincter
What foods travel through the stomach quickly?
Liquids pass through the stomach quickly, however oils do not pass as quickly
Is the area of the stomach always the same?
No it can be as low as 50mL in fasting state, and can expand to 1.5L when filled with food
What is the environment of the stomach like?
Very acidic, the resting pH = 1.5-3
Acids and gastrin are released
What causes the release of acid from the stomach?
Food enters the stomach and buffers the pH.
As soon as this drops down to 5 or 6 gastrin is released. This hormone then causes the stomach to secrete acid
How is pepsin secreted in the stomach?
As a precursor called pepsinogen
Where does digestion really start?
In the stomach.
The acid and pepsin start to act on proteins, carbs, etc. and start to digest them
Mucous is also secreted to protect stomach from enzymes and acid
What happens if the mucous in the stomach is deficient?
You can get gastric ulcers from the acid in your stomach
What is the role of the small intestine?
It completes the process of digestion
Why is the small intestine the major path of absorption?
It contains a vast surface area
What is the small intestine divided into?
What mechanisms does the SI have which increases the surface area for absorption?
Foldings on the cellular level called folds of kerchring
Microvilli on each of the villi
What is another important factor to consider when designing an oral drug?
The transit time.
Normally in the SI, this is 3.5-4.5 hours
What can we use in drug design to make use of the transit time?
We can use atoms to delay the passage so that more of the drug can be released and absorbed
We can use polymers and networks that absorb water and swell
How does lightweight delay passage of drug in the SI?
If a drug is designed to be lightweight, it can float on the surface of the gastric juice, so will delay the passage of the SI
How does the colon compare with the small intestine?
It is a lot shorter, and not as folded --> so much lesser surface area
The villi and microvilli are not present
What is the main function of the colon?
To absorb water
Does the colon have any folds?
Yes, it does have some, but not as much as the SI.
The colon's overall surface area is 10-15x less than the SI
What other things does the colon absorb?
Ions such as Na and K
Why are microflora important in the colon?
They are most abundant in the colon.
We can utilise these to our advantage by designing pro-drugs, which can be activated by these bacteria
What other type of activation system can we use?
PH activation systems
What is the average transient time of the colon?
Quite long, about 24 hours.
How can we use the transient time of the colon to our advantage?
We can have the tablet or delivery device which has preliminary coatings on the surface to protect it from being digested from enzymes in the stomach and SI.
This will ensure the drug is delivered to the colon to be absorbed there, i.e. Targeting the colon
What are two main different routes of absorbption?
Transcellular routes which include passive diffusion, facilitated diffusion and active transport,
Paracellular routes which is where substances travel in between the cells
What is passive diffusion?
Transport mechanism where:
Driving force = concentration gradient, i.e. From high conc, to low conc.
The main mechanism for small, lipophilic molecules
What is active transport?
Transport mechanism which:
Requires energy (ATP) to move molecules against the conc. gradient
These ATP channels can be saturated, this can become a rate limiting step.
Another problem is competition of another substance to the binding site, this can also lead to saturation
What is facilitated transport?
Transport mechanism involving carriers within the bilipid membrane of the SI that will take some drugs
This can also be saturated
This is not the major route of absorption
What is endocytosis?
A transport mechanism which absorbs macromolecules
It is attached to the plasma membrane of cells.
Macromolecules are engulfed and pass to the other side.
Some vaccines and antibodies are good candidates to be delivered this way.
Can have specific antibodies on the drug recognised by receptors on cell membrane to be endocytosed.
What is the paracellular route of absorption?
Mechanism of transport for small molecules, usually water, which is able to pass through the gaps in between the cells
This is not a major route
This is only able to occur as the SI is relatively leaky
What is efflux..
Counter absorptive process where some drugs are rejected and expelled back into the GIT
This is a protective function of the body to remove toxins and unwanted material.
What is the example of efflux and why must it be inhibited?
P-glycoprotein is subjected to this mechanism
However this needs to be inhibited so that the right concentration of PG enters the circulation
What are the common barriers to drug absorption via the oral route?
The lumen of the GIT can cause degradation, complexation of the drug with food and other substances
The absorption through the surface of the GIT and mucous are rate limiting factors for drug delivery
If the drug is too hydrophilic it will be excreted
If the drug is altered to be able to pass through the mucous layer, the next rate limiting step is the plasma membrane.
What is the solution to all the barriers of drug absorption via the oral route?
We need to administer high doses orally, so that we have enough of the active ingredient reach the bloodstream to act on the site of action
What are the four kinds of controlled released tablets discussed?
Enteric coated tablet
Osmotic release device
Capsule with osmotic layer
Tablets coated with chirosan
What are the main components of the enteric coated tablet?
The first layer is the sugar coat which masks the taste of medicication
Enteric coat is next, this is a polymer and is resistant to degradation by acids and enymes
The main purpose of this tablet is to deliver the drug to the SI
How can polymers be used for extended release?
They can be used as different tablet coatings.
There are a range of polymers to choose from for the desired action
What are the main components of the osmotic drug release device?
The polymer is in drug solution (can be in solution or suspension)
When the device is in the GIT it starts to absorb water due to the high osmolarity within the system,
This causes the drug to be released as the pressure builds up
What are the main components of the capsule osmotic layer?
Also has a reservoir which contains the drug, in solution
There is also a tube which pushes the drug out