Lec. 4 - Pharmacokinetics (cont'd) Flashcards
Why are some 3 components that effect magnitude of drug effect
Pharmacodynamics
Pharmacokinetics
Individual properties (is individual user of said drug already? Age? Sex? Etc.)
What is the Vad?
Volume of apparent distribution:
Amount of drug in the body, basically a description of where drug goes
How do plasma proteins affect Vad?
If drug clusters to plasma proteins (ex. Albumin) -> smaller AVD (stays in bloodstream)
If drug diffuses right away -> larger AVD (starts having effect)
What is elimination?
The conversion of drug to less active (or inactive) metabolite, which is usually more water soluble too.
Where is the principal site of metabolism?
Liver
Where else can we find drug metabolizing enzymes (other than liver)
Small intestine
Lungs
Brain
What is the pathway of a drug when entering the liver?
Enters through the portal vein, then flows through sinusoid
What are the 2 phases of drug metabolism?
Phase 1: Oxidation/Reduction/Hydrolysis
Phase2: Conjugation
What enzymes mediate oxydation of metabolism?
Cytochrome P450 (CYP450)
What is the nomenclature for CYP450s?
Ex. CYP3A4
CYP- Cytochrome 450
3 - Family
A - Subfamily
4 - Gene
What are the main families of CYP450 mediating drug and xenobiotic breakdown?
CYP1, CYP2, CYP3
What is enzyme induction/inhibition
Exposure to certain chemicals/drugs/environmental factors can trigger induction/inhibitions of enzyme production
Why is pharmacogenetics an important area of study?
Depending on individual genetic variation, we may see significantly different responses
What is polymorphic distribution?
Give an example
A trait that has differential expression in >1% of the population
CYP2D6 -> absent in 7% of Caucasian’s and 1-2% of non-caucasians
What is the second phase of metabolism?
Conjugation
Describe conjugation
Transfer a chemical group onto the metabolite from phase 1 (oxidation)
What molecule mediates conjugation?
Transferase enzymes
“Metabolism creates an inactive metabolite”. Is this always true?
Give an example
No, in some cases the metabolite is still biologically active.
Ex. Codeine -(phase 1)-> Morphine
What organ is generally the site of excretion?
Kidney
What are the 3 phases of kidney excretion?
Filtration
Secretion
Réabsorption
How does Vad relate to excretion?
If a drug has a low Vad due to being albumin-bound, it’s rate of excretion will be lower (because the albumin won’t pass into the glomerulus)
What is drug clearance?
Volume of body fluid cleared per time. Quantifies the elimination.
What is the equation for total body clearance?
Cl(total) = Cl(hepatic) + Cl(renal) + Cl(pulmonary) + Cl(other)
How is time course of elimination usually denoted?
the half life (t1/2)
How does the initial dose affect the rate of elimination?
It doesn’t, it’s a rate of decay
How long does it take to eliminate a drug from a system?
4 x t1/2
How can overdose affect rate of drug elimination?
Usually, drugs follow first order kinetics, ie a constant fraction metabolism per unit time
However, OD can kick metabolism into zero order kinetics -> constant amount of metabolism per unit time
Why does over dose cause zero order kinetics?
The enzymes mediating the metabolism are saturated
What is a steady state of drug administration?
Nice, therapeutic constant.
Attained after 4 oral administrations at t/12
