Pharmacokinetics

Question 1

What are the 4 stages of pharmacokinetics?

Answer 1

Absorption, distribution, metabolism, elimination

Question 2

Where does the most drug absorption take place?

Answer 2

Most in SI: 6-7m, 3-5 hrs, pH 6-7. SA ~ 30-35m2

Question 3

In the absorption stage how does facilitated diffusion take place?

Answer 3

Solute carrier (SLC) transport = either OATs or OCT = organic anion/cation transporters. Ionic +ve or –ve charge carried across

Question 4

When is passive diffusion used in pharmacokinetics?

Answer 4

Common mechanism for absorption for lipophilic drugs weak acids/ bases: Lipophilic drugs e.g. steroids diffuse directly down conc gradient into GI capillaries, Weak acids/bases protonated/deprotonated species can diffuse

Question 5

What are the factors affecting absorption?

Answer 5

Physicochemical factors = drug lipophilicity, pKa, density of SLC.

GI physiology = blood flow, motility, pH

Question 6

What is bioavailability and how is it calculated?

Answer 6

fraction of a defined dose which reaches its way into a specific body compartment. IV = 100%.

For other routes we compare against IV.

oral = Area under curve oral / AUC IV (answer in decimal)

Question 7

How are drugs distributed?

Answer 7

Bulk flow = large distance, via arteries

Diffusion = capillaries (diff levels of permeability) - interstitial fluid - cell membrane – target

Question 8

What is Vd?

Answer 8

Volume of distribution

represents degree to which a drug is distributed in the body tissue rather than the plasma

= drug dose / [plasma drug]t=0 (smaller value = lower penetration)

Question 9

What are the factors affecting distribution?

Answer 9

Vd

Drug molecule lipophilicity/hydrophilicity = if lipophilic it can move across plasma membrane.

Degree of binding to plasma/tissue proteins = only free drugs can bind targets, binding plasma decreases availability – plasma/tissue act as drug reservoir

Question 10

What happens in phase I metabolism?

Answer 10

enzyme cytochrome p450, metabolise wide range, increase ionic charge of drug = increase renal elimination. Can activate pro-drug = codeine to morphine

Question 11

What happens in phase II metabolism?

Answer 11

cytosolic enzymes – more rapid kinetics, further increase ionic charge = increase renal elimination

Question 12

What is cytochrome p450?

Answer 12

3 superfamilies’ CYP 1, 2, 3, six isoenzymes met ~90% prescription drugs.

Can be induced = plasma levels decrease, can be inhibited = plasma levels increase

Question 13

What are the factors affecting metabolism?

Answer 13

age, sex (alcohol met slower in F), general health (especially hepatic disease), CYP450 inhibition, genetic variation of enzymes (poor, normal/high, ultrarapid metabolisers)

Question 14

Where does drug metabolism take place?

Answer 14

Liver

Question 15

Where does the majority of drug elimination take place?

Answer 15

kidney

Question 16

What can the drug elimination stage remove?

Answer 16

Removes both exogenous (introduced from outside) and endogenous (originate within) molecule species. Recognises xenobiotics = foreign chemical substance

Question 17

What are the three stages of drug elimination?

Answer 17

1) Glomerular Filtration –> 20% renal blood.
2) Active tubular secretion –> Proximal tubular secretion = 80% blood = High OAT/OCTs, active transport of ionised molecules out.
3) Passive tubular reabsorption –> Distal tubular reabsorption = passive reabsorption of unionised drugs, OAT/OCTs

Question 18

What is total body clearance and how is it calculated?

Answer 18

CL: volume of plasma that is completely cleared of the drug per unit time = hepatic clearance + renal clearance.

Predicts how long drug will stay in the body. Plasma can never be fully cleared

Question 19

Define drug half-life

Answer 19

t1/2 = amount of time over which the conc of a drug in the plasma decreases to one half of that conc value it had when it was first measured

Question 20

What is drug half-life dependent on?

Answer 20

Vd and CL

Question 21

What is pharmacokinetics?

Answer 21

what the body does to the drug

Question 22

What are the 2 types of drug administration?

Answer 22

enteral and parenteral

Question 23

What is enteral drug administration?

Answer 23

oral, sublingual, rectal

Question 24

What is parenteral drug administration?

Answer 24

IV, subcutaneous, intramuscular

Question 25

What are the 3 methods for drug absorption?

Answer 25

passive diffusion, facilitated diffusion, active transport

Question 26

What is first pass metabolism?

Answer 26

drugs travel to liver via hepatic portal vein, metabolised before reaching systemic circulation

It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall

Question 27

What genetic factor do CYP enzymes show?

Answer 27

genetic polymorphism

some CYP enzymes are expressed more than others in differing nationalities

Question 28

When does zero kinetics occur?

Answer 28

when there is full saturation of CYPs or transporters

Unequal half-life

Question 29

What does polypharmacy lead to?

Answer 29

zero kinetics as there is more competition for active sites

Question 30

In pharmacokinetics what type of graph shows linear kinetics?

Answer 30

log graph of time vs drug conc in plasma

Question 31

In pharmacokinetics what is the advantage of linear graphs?

Answer 31

can determine half-lives easier

Question 32

How does CYP450 metabolise drugs?

Answer 32

Oxidation, hydrolysis, hydroxylation