Pharmacokinetics (K3) Flashcards
Karen lecture 3 of 4
What is meant by pharmacokinetics
- How the body acts on the drug at any stage during absorption, distribution, Metabolism and elimination
Why is it important that we chose the right method of drug delivery based on its pharmacokinetic profile
- If the body cannot absorb or eliminate the drug, its not effective
What does this schematic tell us?
- The drug is either absorbed in the small intestine into the blood stream or injected directly avoiding first pass metabolism
- It either binds to the blood acting on the blood, remains free being distributed to the target site or is eliminated and excreted.
What is a danger of distribution in this diagram?
- The drug will act on tissues that are not the target site causing other undesirable effects
What is the issue linked to drugs having to pass through lots of barriers like the epithelial wall, small intestine wall and endothelial walls?
- Longer time for the drug to take effect
- Also some drug is eliminated during the diffusion
There are many types of epithelium, how do hydrophilic and lipophilic drugs interact with these?
Lipophilic drugs are able to interact with cells and pass through them via a transcellular route (active transport, diffusion or endo/exocytosis)
Hydrophilic drugs find it harder to break through the lipid bilayer, but very small molecules can diffuse between cells, via the paracellular route
What features of epithelium make it a barrier for cell absorption? (4)
- Mucus coating - acts as a protective barrier
- Cell membrane lipid bilayer is a physical barrier to hydrophilic drugs
- Cell junctions are a physical barrier to paracellular (between) transport
- Efflux system on apical surface (reduces transcellular flux of some drugs)
What types of membranes are more and less susceptible to passive diffusion
More: Blood vessel linings, since they are designed to be leaky enabling lots of transport
Less: The blood-brain barrier, incredibly hard to diffuse through
What other factors can effect drug absorption?
- Higher blood flow (maintains a high conc. gradient of the drug)
- Net surface area (eg, smokers and children have a smaller lung SA)
- Properties of the drug:
Molecular weight, lipid solubility, solubility in extracellular fluids, stability
What is meant by distribution in drug delivery?
The process by which a drug is transferred from the circulatory system to its site of action
What are the main factors that effect how much drug and how quickly the drug gets to the target site when thinking about distribution?
- Level of blood flow, some tissues are better perfused with blood vessels than others
- Drug binding to plasma proteins - A bound drug will stay in the blood rather than reach the target site
What is the meaning of volume of distribution?
- This is the volume into which the drug distributes
What is the equation to calculate the volume of distribution?
What factor can the volume of distribution effect?
The drugs half life, aka how long the drug is active for
Define metabolism of drug
- The chemical alteration of a drug by the action of an enzyme
What is going on in this diagram?
Phase 1: The drug is actively metabolised into its derivative
- The derivative is a non-active form but still needs to be removed
Phase 2: The derivative undergoes conjugation in which the body further metabolises the drug to convert it into a conjugate, aka. a hydrophilic molecule that’s easy to excrete and remove
Why is it important that drugs are metabolised into hydrophilic metabolites for excretion of these byproducts?
- After filtration and absorption in the glomerulus and nephron of the kidneys, all lipid soluble drugs are still in the blood because they are bound to proteins and cells
- Hydrophilic metabolites are pressed out of the blood by hydrostatic forces in the glomerulus, and are not reabsorbed
What is the simplest equation for rate of elimination?
CLr (renal clearance) = the volume of renal plasma from which all substance is removed in a given time
Cp = drug concentration
What is the equation for renal clearance, that takes into consideration the urine conc and urine flowrate
What does this graph and the equation show?
Graph - shows the log reduction in drug concentration vs time (first order)
Equation - Total clearance (All the routes of drug exit, renal, lung sweat…) is equal to the slope of the log curve (elimination rate constant) * volume of distribution
What does this tell us about people who have a larger Volume of distribution?
If Vd is higher and the elimination rate constant is kept the same, then a higher blood volume equates to a faster rate of clearance (removal)
What is the equation to calculate the half life of a drug?
What would an IV injection drug conc profile look like if there were no elimination and with elimination
