Drug Absorption into blood Flashcards
What 2 ways do drugs move around the body
1- bulk flow: move in blood often bound to proteins like albumin
2- diffusion: across barriers such as cellular membranes
Which type of drug can freely move across barriers
Unionised/lipid soluble (from high to low conc)
How do water soluble drugs cross barriers/membrane
Aqueous channels
How can drugs move across via carrier proteins
Either passively down electrochemical gradient OR using ATP binding cassettes from low to high conc
What is drug administration into the skin called and where does it go
Percutaneous
Drug goes straight to plasma
Which way of administration causes 100% of the drug to enter the plasma
Intravenous (into vein)
What route do oral or rectal administration take
To the gut where they can enter blood or liver via portal vein
Where does drug go after the gut if not to the plasma to be excreted
Kidney and then excreted as urine or faeces
What is administration into muscle called
Intramuscular
What is intrathecal administration
Into cerebrospinal fluid
Is inhalation a way of administration?
Yes , Gas or powder
What is the word given to drug moving into cell and out of cell
Into cell = influx
Out of cell = efflux
Which route is best for steady state absorption
Percutaneous/dermal (skin)
When are 4 times injections used
When drugs are poorly absorbed
Fast metabolism of drug in gut
For fast action
Dose control required
What is a single injection and constant injection called
Single = bolus
Constant = infusion
What are 3 types of injection
Intravenous (fast response)
Intramuscular (slow diffusion)
Subcutaneous (skin injection)
How are intramuscular injections taken
Through depot injection which is oil based for slow diffusion
With oral administration it goes to the gastrointestinal tract
Which part of the tract isn’t site of absorption
Stomach - ph is too acidic it would ionise drug
What are 3 adaptations of the small intestine good for absorption by oral intake
1- microvilli = increase SA
2- vascularised- good blood supply
3- enterocytes which contain transporters for drugs
Which carriers do enterocytes have to the gut lumen or to the blood
Passive channels
Atp binding cassettes for efflux against conc gradient
What is bad about enterocytes
They contain metabolic enzymes which can degrade drug before it’s passed into the blood
Where do drugs influx to from the enterocytes in small intestine
Into blood stream then to liver via portal system
Why do drugs sometimes efflux out of gut wall into the gut lumen again
To stop body from harmful substances by the drug so it can be excreted to the kidney
why is the liver a bad place for drugs to go from the gut wall
Because it is site of metabolism like enterocytes are
Can affect drug absorption
What is the drugs called which don’t get metabolised by the liver by first pass metabolism and where do they go
Bioavailable drugs
Go to the systemic circulation
What is enterohepatic recirculation
Where drugs from the liver to back to the gut and to the gut wall to restart the cycle
Name some first pass metabolised drugs
Aspirin , propanolol, lidocaine
What are 2 gastrointestinal routes other than oral which stop first pass metabolism
1- sublingual (spray under tongue into circulation)
2- rectal suppositories
Why does rectal administration only stop 2/3 of first pass metabolism
The superior vein in the rectum goes to the portal vein and then to the liver for first pass metabolism
What are 5 ways of administration which aren’t gastrointestinal (don’t get metabolised first pass)
= PARENTRAL
Inhalation (powder or gas)
Cornea
Nasal (spray)
Vaginal
Transdermal (skin patch)
Why is vaginal administration not always good for absorption
Ph can change for example in menstruation
Changes the ionisation of the drug
Give an example of transdermal parentral administration
Stick on patches for hormone therapy
What are 6 factors affecting drug absorption
Size of drug Membrane permeability Skin hydration - better if hydrated Pka of drug Metabolism of drug Lipid solubility of drug (better if so)
Why is ph affecting crossing of the membrane
Because if ionised then they can’t be lipid soluble
When are acidic drugs ionised so can’t pass membrane
When in alkali conditions
When are alkaline drugs ionised
When in acidic conditions
What is it called exploiting ph of drug to cause excretion
Ion trapping
Why does solubility of drug in water cause increased levels of absorption in GI tract
They can pass through aqueous channels at the enterocytes
What are the 4 classes of drug
Class 1- high water solubility and high permeability (unionised)
Class 2- low water solubility but high permeability (unionised)
Class 3- high water solubility but low membrane permeability
Class 4- low solubility and permeability
Why is class 2 excreted before entering GI tract
Because they can’t be solulised in the GI tract
Why is class 3 high in conc at the GI tract but low absorption
Because it has high solubility increasing its conc in Gi tract but can’t pass the membrane due to being ionised
How does gastric motility affect absorption if a drug is taken orally
If they have slow gastric motility the affect of the drug will also be slow
Why would too fast gastric motility cause lack of absorption
It would be excreted before being absorbed into the gut wall
Why would taking drugs with food increase absorption/ rapid response
Because it will increase flow of digestive system
What on drugs affect it’s ability to be absorbed
The capsule
What is Cmax and Tmax
Cmax = max concentration of drug in plasma
Tmax = time of max conc in plasma
How would you calculate total drug exposure
Split area under curve into trapeziums then do
average plasma conc x time interval of the area
Add all together
How would you calculate bioavailability of the drug
(Exposure orally / exposure intravenous(100%))
X
(Dose of intravenous / dose of oral)
What is Ka
Rate of absorption
What does a lower Tmax mean for Ka
Lower Tmax(time of max conc) = higher Ka (rate of absorption)
What are you trying to achieve when taking repeated doses orally compared to fast IV
Steady state
What is C0
Concentration in circulation at time O due to immediate distribution (one compartment model)
How do you work out C0 (conc at time 0)
Dose / Vd
