PHAR232 - pharmacokinetics wk 5 Flashcards
What is pharmacokinetics?
Pharmacokinetics is the study of how the body absorbs, distributes, metabolizes, and eliminates drugs.
What are the 4 key areas of pharmacokinetics?
The four main processes of pharmacokinetics are:
Absorption: This is the process by which drugs enter the bloodstream from the digestive tract, skin, or other tissues.
Distribution: This is the process by which drugs are transported throughout the body.
Metabolism: This is the process by which drugs are broken down by the liver and other organs.
Excretion: This is the process by which drugs are excreted from the body, typically through the kidneys or liver.
What are tissue reservoirs?
A place where a drug can hide e.g. fat cells
Where is the major site for metabolic biotransformation?
The liver
What is the primary organ for excretion?
Kidney function
CV intergrity
When you age do you lose plasma protein?
Yes
What’s the role of pharmacokinetics in research?
- Invsestigate implications for developing foetus
- Designing safe and effective doses
- Amelioration of disease
- Inter-species variability (animals vary massively)
What is the accronym for the basis of Pharmacokinetics?
L=Liberation= release of drug from formulation
A = Absorption - update of drug into circulation
D = Distribution - Movement of drug between body compartments
M = Metabolism - effect of ENZYMES on drug
E = Excretion - Removal of unchanged drug or metabolite from body
What is the addition term for ‘metabolism + excretion’?
Elimination
What is the additional term for ‘Distribution + elimination’?
Disposition
The are the key family of liver metabolic enzymes?
CYP450 family
What phase of detoxification does CYP450 enzymes convert drugs/metabolites to?
Phase I
Is the metabolite (offspring) the same as the drug (parent)?
No e.g. if 100% of the drug was metabolised, there is no more DRUG. The drug no longer exists.
How do you evaluate systemic drug exposure?
- Circulation: Plasma, serum, whole blood
- Products: milk, urine, saliva, exhaled air
UNDERSTAND MORE ABOUT PLASMA DRUG CONCENTRATIONS
WHAT MATTERS IS THE FREE-UNBOUND DRUG IN PLASMA
Bound to plasma protein = CANNOT EXERT AN EFFECT
Measurement of plasma concentration = bound & unbound
MUST KNOW KINETICS and how much is bound and effective concentration
What are disadvantages of plasma drug concentration evaluation?
- Measurement of plasma concentration = bound & unbound drug
- Assumes good integrity of circulation (atherosclerosis etc)
- Assumes homogenous distribution of drug e.g equilibrium of drug between plasma & tissues (intereference)
UNDERSTAND MORE ABOUT COMPARISON OF PLASMA & WHOLE BLOOD CONCENTRATIONS FOR DRUG EVALUATIONS
What is the exposure-time profile determined by?
- Rate of drug administration
- Dose administered at this rate
- Distribution
- Rate of elemination
What does Cmax stand for?
Maximum concentration of drug
What does tMax stand for?
Time of maximum concentration
What does AUC stand for?
Area under the curve
(exposure)
If a curve is steep in an exposure-time profile, what does this mean?
It’s the rate of absorption
What does the half-life of a drug mean?
The half-life of a drug is the time it takes for half of the drug to be eliminated from the body.
E.g 50%, 50%, 50%, 50%
Can you only clear what the system sees as a free-drug instead of a bound drug?
Yes
What is clearance (CL)?
Quanity of blood that has drg removed from it over a period of time e.g.
Uniters = volume per unit time = ml/min or L/hr etc.
Relates to ORGAN doing the clearance
What is volume of dristribution (Vd = V)?
a THEORETIC VOLUME - NOT AN ACTUAL
BODY DISTRIBUTION and ASSOCIATION with cellular proteins
Vd = V example
it’s an IDEA, of the ease with which the drug distributes, and the extent to which it MIGHT be found in tissues.
Reflects the POTENTIAL ability of the drug to DISTRIBUTE TO THE TISSUES
Cmax = maximum concentration
= How QUICKLY the drug is being absorbed vs how QUICKLY the drug is being eleminated
If absorbing SLOWLY you would be ELIMINATING as you absorb
Does the time to maximum concentration change with a higher dose?
No
LOOK AT
Exposure is the same in both A & B charts
PEAK IS DIFFERENT
And that can make a difference in toxicity
E.g. slow release vs rapid release drugs
What does Area under the curve represent? (AUC)
Index of total systemic exposure to drug
How do you determine the AUC?
- Use the curve data points to add up the INDIVIDUAL PIECES
e.g. difference between red dots in the attached
Then ADD them up
Trapezoid rule
Where is usually the Y and X axis on a chart?
Y-axis: vertical axis, left side of a chart,
x-axis: horizontal axis , bottom.
First pass metabolism
First pass metabolism:
- Gut lumen
- Gut wall
- Portal vein
- Liver
- Metabolism
- Biliary excretion
- Faeces
Disposition = what combination?
Distribution + elemination
What is disposition influenced by?
- Organ blood flow
- Organ size
- Binding of drug to blood proteins & tissues
- Membrane transport
What regulates penetration of a drug?
Surface area x permeability of the membrane
e.g. size, proteins, concentration gradient, lipophilic?? etc
(plasma vs tissue gradient)
Disposition to the tissue cycles
What is a common error when thinking about ELIMINATION?
ERROR: That elimination ONLY refers to excretion
FACT: ELIMINATION = metabolism + excretion
How would the evaluation of a drugs metabolism be recognised in urine?
- % of drug UNCHANGES IN URINE
- % of METABOLITES in urine
What does pKa stand for?
pKa stands for “acid dissociation constant” or “dissociation constant of an acid.
50% of the molecule is IONISED & 50% of the molecule is UN-IONISED
What’s the difference between ionised and un-ionised drugs?
Un-ionised: cross membranes
Ionised drugs: do not cross membranes
e.g. un-ionised drugs are more potent as they have more exposure to cytosol
Is a weak base ionised or unionised?
Mostly unionised
The lower the pKa value, the more ionized or unionised the base will be?
ionized
What pH level or above does it need to be ionised?
11 - 14 pH scale
What are the 3 ways that you discover and develop new drugs?
- Drug modification (build on excisting drugs)
- Natural product chemistry
- Ethnopharmacology (indigenous groups and asking what they use for ancient traditions)
