56. Movement of drugs through the body: Drug absorption and distribution

Question 1

what is Pharmacodynamics

Answer 1

what the drug does to the body.
drug acting at a particular drug target resulting in the activation or inhibition of a cellular signalling pathway and eventually resulting in a change in a physiological process.

Question 2

what is Pharmacokinetics

Answer 2

what the body does to the drug!

how easily the drug is absorbed in the body, is the drug distributed in certain tissue more than others, how the body metabolises the drug or eventually excretes it.

Question 3

affinity

Answer 3

Ki

Question 4

Potency

Answer 4

EC50

Question 5

efficacy

Answer 5

Emax

Question 6

absorption rate constant

Answer 6

Ka

Question 7

If you have a very high Plasma Concentration of a drug what does this do

Answer 7

toxic effects

Question 8

if you have a very low Plasma Concentration of a drug what does this do

Answer 8

Sub-Therapeutic effect

Question 9

if you have a middle of the road Plasma Concentration of a drug what does this do

Answer 9

therapeutic effects - THIS IS WHAT WE WANT

Question 10

so why is pharmacokinetic analysis important

Answer 10

helps us determine a dose of drug that will result in the appropriate blood plasma conc. to be safe and effective

Question 11

what is ADME

Answer 11

absorption
distribution
metabolism
excretion

Question 12

how do drugs move around in the body

Answer 12

Bulk Flow- this would be via the circulatory system (blood stream)

Diffusion of drug molecules over short distances

Solubility is important- lipid soluble drugs are more likely to diffuse across lipid bilayer membranes

Question 13

how fast do large drug molecules move in comparison to small ones

Answer 13

Large drug molecules move more slowly than small one

Question 14

Name the 4 ways in which drugs can cross cell membranes

Answer 14

Passive diffusion
facilitated diffusion
Active transport
Endocytosis(Pinocytosis)

More info down here
1. Passive Diffusion directly through the lipid or through aqueous pores formed by aquaporins that transverse the lipid bilayer. Many lipid soluble drugs cross cell membranes in this way.
2. Facilitated Diffusion via specialised carrier proteins that bind the drug on one side of the bind molecule on one side of the membrane then change conformation and release on the other side. Does not require energy, but does require a concentration gradient
3. Active Transport via specialised carrier proteins Requires Energy and can move drug molecules against the concentration gradient.
4. Endocytosis (pinocytosis)- invagination of a part of the membrane. The drug is encased in a small vesicle then ‘released’ inside the cell.

Question 15

the ……. the log p the greater the lipid solubility

Answer 15

greater

Question 16

what are the principal sites of carrier mediated drug transport (both facilitated diffusion and active transport)

Answer 16

1. Blood brain barrier
   
   2. Gastrointestinal Tract
   3. Placenta
   4. Renal Tubule
   5. Biliary Tract

Question 16

Many drugs are ‘…….’ acids or ‘……’ bases

Answer 16

weak

Question 17

endocytosis transports what kind of drugs and give an example

Answer 17

large drugs eg vitamin B12

Question 18

the proportion of ionisation of a drug depends upon both the ‘’’’’’ of the drug and the local ‘’’’’’’

Answer 18

pKa
pH

Question 19

what are the base and acid ionisation equations

Answer 19

BH+ <—> B + H+
AH <—> A- + H+

Question 20

The ………… equation can be used to determine proportions of ionised and un-ionised drugs in a given pH environment

Answer 20

Henderson-Hasselbalch

Question 21

what are the Henderson Hasselbalch equations for acids and bases

Answer 21

pKa= pH+log(AH/A-)
pKa= pH+log(BH+/B)

Question 22

what is aspirins pKa

Answer 22

3.5

Question 23

negatively charged aspirin diffuses across the membrane of th egastric mucosa and gets……….

Answer 23

trapped in the plasma
good absorption

Question 24

absorption of weak acids is facilitated where

Answer 24

pH of the stomach lumen

Question 25

absorption of weak bases and majority of absorption (even weak acids) happens where

Answer 25

small intestine

Question 26

if they have a pKa above 10 or below 3 (aka strong acids/bases) they are

Answer 26

poorly absorbed

Question 27

Ionised (Charged): These forms are usually ……. (hydrophilic) and find its easy/hard cross lipid cell membranes.

Answer 27

water-soluble (hydrophilic)
hard to cross lipid cell membranes.

Question 28

Unionised (Uncharged): These forms are typically ……(lipophilic) and can/can’t cross cell membranes

Answer 28

lipid-soluble
can

Question 29

where does most oral route drug absorption occur and why

Answer 29

in the small intestine due to the large surface area

Question 30

The Apparent Volume of Distribution (Vd) equation

Answer 30

Vd = dose/drug(plasma)

Question 31

Lipophilic drugs cross membranes easily and Vd is generally ………..than total body volume.

Answer 31

greater

Question 32

It is more difficult for hydrophilic or ionized drugs to cross membranes so Vd is closer to total body volume of water. what is the total body volume of water

Answer 32

42 L

Question 33

If you have a low Vd what does this mean

Answer 33

drugs are retained in vacular compartments

Question 34

If you have a high Vd this means?

Answer 34

it has spread to tissues and non vascular compartments, muscle and adipose

Question 35

give an example of a drug which is hydrophilic or ionised with a Vd=10

Answer 35

aspirin

Question 36

give an example of a drug which is lipophilic or unionised with a Vd of 1221

Answer 36

Amitriptyline

Question 37

if two drugs have equal potency which drug will need a larger dose. the drug with a high Vd or a low Vd

Answer 37

high

Question 38

what is the most abundant plasma protein that binds to mostly acidic drugs.

Answer 38

Albumin

Question 38

what other plasma proteins bind drugs

Answer 38

Beta globulin and acid glycoprotein

Question 39

High protein binding can slow drug elimination by….

Answer 39

preventing metabolism in the liver and glomerular filtration

Question 40

Plasma protein binding reduces what

Answer 40

the availability of the drug for diffusion to the drug target organ

Question 41

what is pKa

Answer 41

the measure of acidity or basicity of a drug molecule
It is also the pH of the solution at which 50% of the drug will be ionised and 50% will be unionised.