Pharmokinetics 2

Question 1

How is SA maximised in SI?

Answer 1

Plicae circularis
Villi
Microvilli

(30-35m2)

Question 2

What is bioavailibility?

Answer 2

Fraction of defined dose which reaches specific body compartment
(circulation cost common ref compartment)

Question 3

What is IV reference value bioavailabilty CVS?

Answer 3

100% - all reaches CVS

Question 4

How are other routes of bioavailability compared?

Answer 4

Reference intravenous bioavailability (eg oral/IV)

Question 5

Factors affecting drug absorption

Answer 5

Physiochemical
GI Physiology
First pass metabolism - GI and Liver

determine proportion of drug entering systemic circulation

Question 6

How do measure bioavailability?

Answer 6

Plot plasma conc against time post dose
Calculate area under curve

for oral - area under oral curve/area under IV curve

Question 7

Oral availability equation

Answer 7

F = amount reaching systemic/drug given IV

AUC

Question 8

Where does F (bioavailability) lie?

Answer 8

Between 0 and 1

1 = all to systemic
0 = none to systemic

Question 9

Drug distribution

Answer 9

How drugs travel through the body

• therapeutic/non therapeutic (side effects) interactions
• Interactions with other molecules

Question 10

First stage - 3 parts distribution

Answer 10

Bulk flow: large distance via arteries –> capillaries

Diffusion: capillaries –> interstitial fluid –> cell membrane targets

Barriers to diffusion: Interactions/permeability/non target binding

Question 11

Diffusion across capillaries affected by

Answer 11

Level of permeability

Expression of endogenous transporter/OAT, OCT

Question 12

3 types capillaries

Answer 12

Continuous (closed, tight gap junctions, tight intercellular cleft)

Fenestrated (less tight cleft. fenestrations)

Sinusoid (leaky sinuses. big fenestrations)

Question 13

Continuous found

Answer 13

BBB
CNS
Muscle
Skin
Fat

Question 14

Fenestrated found

Answer 14

Intestinal
Endocrine/exocrine glands
Kidney glomeruli

Question 15

Sinusoidal found

Answer 15

Bone marrow
Lymph
Liver
Spleen

(allow cells out)

Question 16

Large effect on pharmacokinetics is…

Answer 16

Heterogenous structures/tissues of body

Different body types

Question 17

Major factors affecting drug distribution

Answer 17

Lipophilicity/Hydrophilicity

Degree of drug binding to plasma/tissue proteins

Question 18

Lipophilicity/Hydrophilicity

Answer 18

If lipophilic - easily move across membrane

if hydrophilic - barriers are related to absorption barriers (capillary permeabilty, drug pKa, pH, OAT/OCT density)

Question 19

Degree of drug binding to plasma/tissue proteins

Answer 19

Drugs bind to proteins in circulation

eg. Albumin (globulin)
Lipoproteins (acid glycoproteins)

Question 20

Example albumin

Answer 20

If drug bound to albumin acts as ‘dynamic reservoir’ of drug
ONLY FREE DRUG can bind to targets
If drug binds to protein = decreased free drug available

Question 21

Binding to albumin

Answer 21

Binding not strong (equilibrium)

Multiple drugs can bind - competition for binding sites (affects pharmacokinetics)

Question 22

3 body fluid compartments

Answer 22

Plasma water (3L)
Extracellular water (plasma (3) + interstitial (11) 14L)
Total body water (extracellular + intracellular 42L)

Question 23

Barriers at compartments

Answer 23

Capillary membrane barriers (between plasma and interstitial)

Target tissue membrane barriers (between interstitial and intracellular)

Question 24

What does increasing penetration of drug do?

Answer 24

Drug moves more readily from plasma –> interstitial –> intracellular

= decreased plasma drug concentration 
Increased Vd (volume distribution)

Question 25

Where are most drug targets located?

Answer 25

Membrane of intracellular cells Only need to penetrate to interstitial to have effect

Question 26

Why is volume distribution (Vd) apparent?

Answer 26

Group all main fluid compartments as ONE compartment = summary of drug through plasma, interstitial and intracellular Pretend concept

Question 27

What is Vd usually referenced to?

Answer 27

Plasma concentration | dependent on push/pull factors

Question 28

What do values of Vd mean?

Answer 28

small Vd: less penetration of interstitial/intracellular compartment large Vd: greater penetration of interstitial/intracellular compartment

Question 29

Vd units

Answer 29

litres (70kg standard assumed) | Litres/kg (affected by weight)

Question 30

Vd equation

Answer 30

Drug dose/plasma drug (at time =0)

Question 31

What can Vd be affected by?

Answer 31

``` Blood flow Hypoalbuminemia Body weight changes (increased lipid, more to pass through) Other drugs Renal failure - drug excreted slower Pregnancy Paeds Geriatrics Cancer ```