ICPP - Pharmacokinetics Flashcards
What are the four main processes in pharmokinetics?
Absorption, distribution, metabolism and elimination
Summarise the drug administration routes.
ENTERAL (oral, sublingual, rectal) and PARENTERAL (intravenous, subcutaneous, intramuscular)
Where does most drug absorption occur in the oral route?
Most is absorbed from small intestine
What is the typical transit time of the small intestine?
3-5 hours, but motility varies 1-10 hours
What is passive diffusion?
The mechanism by which lipophilic drugs and weak acids/bases diffuse directly down concentration gradient into GI capillaries.
What are SLCs?
Solute Carrier transport, which move anions and cations through the GI epithelia. It is a passive process driven by electrochemical gradient.
Give some examples of factors in the GI tract that can affect drug absorption?
- GI length
- Density of SLC expression
- Blood flow to GI
- Motility of GI
- Whether there is food present/ pH
What are phase I and II enzymes?
Enzymes found in the liver that metabolise enzymes. Phase I = cytochrome P450s.
Phase II = conjugating
What is “first pass” metabolism?
When drugs pass through the liver, which reduces the availability of the drug reaching systemic circulation.
What is bioavailability?
The fraction of a defined dose which reaches its way into a specific body compartment.
Why is the circulatory compartment a common reference compartment?
Because an IV bonus has 100% delivery to veins
How is oral bioavailability (F) calculated?
F = amount reaching systemic circulation (area under curve on oral graph) / total IV drug given (area under curve on IV graph)
F is between 0 and 1, and informs choice of administration route
What are the three varying levels of capillary permeability?
- continuous
- fenestrated
- sinusoid
If a drug is lipophilic, is it easy or difficult to move across the membrane barriers?
Easy
If a drug binds to plasma/tissue proteins, can it bind to the target site?
Not initially, as it must be free to bind. However, bound drug often acts as a “reservoir”, so it would be able to dissociate and bind to target site.
What are the three model body fluid compartments?
Plasma water (3 litres), interstitial water (11 litres) and intracellular water (28 litres). Drugs move from plasma to interstitial to intracellular.
What is apparent volume of distribution?
A (made up) concept that the main body fluid compartments can be grouped together.
Vd = drug dose / [plasma drug] at time=0. Units are litres or litres/kg
Smaller Vd values = less penetration of intracellular fluid compartment, higher Vd values = more penetration
Can the Vd change from person to person?
Yes - it is affected by many factors, for example pregnancy, pediatrics, geriatrics, renal failure
What is the evolutionary advantage of recognising xenobiotics?
They are potential toxins
Which reactions do CYP450 (phase I) enzymes catalyse, and where are they found?
Redox, dealkylation and hydroxylation.
Found on external face of ER.
What are pro-drugs?
A precursor to drugs which must be activated in order to work, eg codeine to morphine
Where are phase II enzymes found and what do they do?
In the cytosol, they enhance hydrophilicity by further increasing ionic charge which allows better renal elimination.
What are the three super families of cytochrome P450 enzymes?
CYP 1, 2 and 3. Six of these isozymes metabolise around 90% of prescription drugs.
Give some factors affecting speed of drug metabolism in humans.
- age
- sex
- general heath/dietary/disease
