Lec. 4 - Pharmacokinetics (cont'd)

Question 1

Why are some 3 components that effect magnitude of drug effect

Answer 1

Pharmacodynamics

Pharmacokinetics

Individual properties (is individual user of said drug already? Age? Sex? Etc.)

Question 2

What is the Vad?

Answer 2

Volume of apparent distribution:

Amount of drug in the body, basically a description of where drug goes

Question 3

How do plasma proteins affect Vad?

Answer 3

If drug clusters to plasma proteins (ex. Albumin) -> smaller AVD (stays in bloodstream)

If drug diffuses right away -> larger AVD (starts having effect)

Question 4

What is elimination?

Answer 4

The conversion of drug to less active (or inactive) metabolite, which is usually more water soluble too.

Question 5

Where is the principal site of metabolism?

Answer 5

Liver

Question 6

Where else can we find drug metabolizing enzymes (other than liver)

Answer 6

Small intestine
Lungs
Brain

Question 7

What is the pathway of a drug when entering the liver?

Answer 7

Enters through the portal vein, then flows through sinusoid

Question 8

What are the 2 phases of drug metabolism?

Answer 8

Phase 1: Oxidation/Reduction/Hydrolysis

Phase2: Conjugation

Question 9

What enzymes mediate oxydation of metabolism?

Answer 9

Cytochrome P450 (CYP450)

Question 10

What is the nomenclature for CYP450s?

Answer 10

Ex. CYP3A4

CYP- Cytochrome 450
3 - Family
A - Subfamily
4 - Gene

Question 11

What are the main families of CYP450 mediating drug and xenobiotic breakdown?

Answer 11

CYP1, CYP2, CYP3

Question 12

What is enzyme induction/inhibition

Answer 12

Exposure to certain chemicals/drugs/environmental factors can trigger induction/inhibitions of enzyme production

Question 13

Why is pharmacogenetics an important area of study?

Answer 13

Depending on individual genetic variation, we may see significantly different responses

Question 14

What is polymorphic distribution?

Give an example

Answer 14

A trait that has differential expression in >1% of the population

CYP2D6 -> absent in 7% of Caucasian’s and 1-2% of non-caucasians

Question 15

What is the second phase of metabolism?

Answer 15

Conjugation

Question 16

Describe conjugation

Answer 16

Transfer a chemical group onto the metabolite from phase 1 (oxidation)

Question 17

What molecule mediates conjugation?

Answer 17

Transferase enzymes

Question 18

“Metabolism creates an inactive metabolite”. Is this always true?

Give an example

Answer 18

No, in some cases the metabolite is still biologically active.

Ex. Codeine -(phase 1)-> Morphine

Question 19

What organ is generally the site of excretion?

Answer 19

Kidney

Question 20

What are the 3 phases of kidney excretion?

Answer 20

Filtration
Secretion
Réabsorption

Question 21

How does Vad relate to excretion?

Answer 21

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)

Question 22

What is drug clearance?

Answer 22

Volume of body fluid cleared per time. Quantifies the elimination.

Question 23

What is the equation for total body clearance?

Answer 23

Cl(total) = Cl(hepatic) + Cl(renal) + Cl(pulmonary) + Cl(other)

Question 24

How is time course of elimination usually denoted?

Answer 24

the half life (t1/2)

Question 25

How does the initial dose affect the rate of elimination?

Answer 25

It doesn’t, it’s a rate of decay

Question 26

How long does it take to eliminate a drug from a system?

Answer 26

4 x t1/2

Question 27

How can overdose affect rate of drug elimination?

Answer 27

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

Question 28

Why does over dose cause zero order kinetics?

Answer 28

The enzymes mediating the metabolism are saturated

Question 29

What is a steady state of drug administration?

Answer 29

Nice, therapeutic constant.

Attained after 4 oral administrations at t/12