Pharmokinetics

Question 1

What does ADME stand for

Answer 1

absorption, distribution, metabolism, excretion

Question 2

2 different types of administration?

Answer 2

Administration can be systemic, where the entire organism is exposed to the drug, or local, where it is restricted to one area of the organism

Question 3

3 different routes of administration?

Answer 3

Routes of administration can also be enteral, so through the GI tract, or parenteral, via everything but the GI tract, inhalational

Question 4

2 examples of sites of parenteral administration

Answer 4

Intraperitoneal (because the peritoneum has a rich blood supply) or intravenous

Question 5

Two ways drugs move around the body?

Answer 5

Bulk flow transfer and diffusion transfer

Question 6

What is bulk flow transfer? When is it used? Example of bulk flow transfer

Answer 6

in the bloodstream where it will move in bulk to the tissues. E.g. intravenous injection. This is when treatment is needed immediately

Question 7

What is diffusion transfer? When is it used? Example of bulk flow transfer

Answer 7

molecule by molecule over short distances. This is for slower, controlled and over a longer period of time administration. This is what happens with tablets and creams etc

Question 8

Methods for crossing barriers that drugs use

Answer 8

diffusing (if the drug is lipid), diffusing through aqueous pores in the lipid (if the drug is polar), carrier molecules and pinocytosis

Question 9

What is the pH of aspirin

Answer 9

Acidic

Question 10

How will an acidic drug fare in the stomach

Answer 10

when acid enters the stomach where the acidity is around pH 1 then it is more likely to stay unionised and non-polar due to the equilibrium. This means in this state it can cross the lipid bilayer and so there is a lot absorbed in the stomach (this can irritate the stomach)

Question 11

How will an acidic drug fare in the small intestine

Answer 11

When the aspirin moves to the small intestine, the pH is much more basic meaning a lot more of the aspirin is likely to become ionised. This makes it a lot more difficult for it to get through the membrane as it is a non-polar phospholipid barrier. This leads to slower absorption in the small intestines

Question 12

What is ion trapping

Answer 12

The unionised form of the drug is mopped up by proteins in the blood. They are basically trapped as such and this is known as ION TRAPPING. This provides another obstacle preventing the drug from being absorbed into tissues.

Question 13

What to do with aspirin to prevent stomach irritation

Answer 13

Enteric coating

Question 14

What are the benefits of enteric coating for acidic drugs

Answer 14

it will resist the stomach acid and only be broken down in the small intestine. Here it can give a prolonged slow release and absorption of the drug, which is useful for treating chronic conditions

Question 15

what does the ratio of ionised:unionised drugs depend on

Answer 15

Transport proteins, and pH

Question 16

4 factors affecting drug distribution

Answer 16

Regional blood flow, extracellular plasma protein binding, capillary permeability and localisation in tissues

Question 17

Explain how localisation in tissues affects drug distibution

Answer 17

fat doesn’t perfuse very well usually (are poorly perfused) so it is found in very lipophilic environments; therefore, drugs that are lipophilic tend to localise and partition themselves into fatty tissues (brain, testes…). This means the drug will persist in the tissue and continue its pharmacological activity in that tissue, e.g. marijuana

Question 18

Explain how Regional blood flow affects drug distibution

Answer 18

tissues well perfused are likely to be exposed to a higher conc. of the drug. Some tissues may increase in perfusion when their activity increases, e.g. skeletal muscle. Highly metabolically active tissues need to be well perfused with a higher blood flow and denser capillary network than less active tissues

Question 19

Explain how extracellular plasma protein binding affects drug distibution

Answer 19

anything bound to a plasma protein is not bioactive and is unavailable for absorption. 50-80% of acidic drugs tend to bind to plasma proteins establishing a dynamic equilibrium. Albumin can bind both ionised and non-ionised drugs

Question 20

Explain how capillary permeability affects drug distibution

Answer 20

small gaps exist between endothelial cells allowing ionised forms of drugs (e.g. aspirin) to pass through. These gaps are aqueous. Capillary architecture can have a significant impact on how well these drugs can travel through (fenestrated/continuous/discontinuous). Also the tissue composition effects absorption, e.g. the brain has a thick lipid blood brain barrier which only allows certain drugs through

Question 21

what’re the 2 main routes of excretion

Answer 21

liver and kidney

Question 22

what are the minor routes of excretion

Answer 22

lungs, skin, GI secretions, saliva, sweat, milk and genital secretions (every body fluid can constrain drugs as drugs partition themselves into it)

Question 23

which organ holds the majority of the responsibility of excreting a drug

Answer 23

Kidnet

Question 24

What does the kidney do to a drug

Answer 24

converts it into something water soluble which is then urinated

Question 25

how do drugs enter the kidney and why

Answer 25

Through active secretion as most drugs are too big to enter through ultrafiltration

Question 26

what happens to drugs regarding excretion in the glomerulus

Answer 26

nothing, drugs aren’t filtered as they’re too big

Question 27

what happens to drugs regarding excretion in the proximal tubule

Answer 27

active secretion of drugs and reabsorption of lipid soluble drugs

Question 28

what happens to drugs regarding excretion in the distal tubule

Answer 28

reabsorption of lipid soluble drugs

Question 29

where are lipid soluble drugs reabsorbed and why/how

Answer 29

in the proximal and distal tubules of the kidneys as urine is an aqueous environment and the drug may have become more unionised and more lipid in the pH of the urine allowing it to be reabsorbed easily

Question 30

what type of drugs are actively reabsorbed in the kidney

Answer 30

Drugs that look like amino acids or glucose

Question 31

why might treatment with sodium bicarbonate cause increased excretion of aspirin

Answer 31

IV sodium bicarbonate will make urine pH higher, this means aspirin is more ionised in the urine, this makes it less lipid soluble and so it is less reabsorbed in the proximal and distal tubules

Question 32

how does the liver contribute to drug excretion

Answer 32

liver picks up drugs from the GI tract, drugs are concentrated in the bile which is then excreted into the intestines

Question 33

What drugs are likely to be disposed of by the liver

Answer 33

drugs with an Mr of 1050 or greater

Question 34

what transport mechanism does the liver employ to get drugs into bile, what is this method meant for and how do drugs get involved

Answer 34

Active transport, meant for transporting bile acids and glucoronides into bile but drugs can hitch a ride as they have a high Mr and can be non-polar

Question 35

What poses a problem for excretion via the liver? what’re the consequences of this problem? what can stop this problem?

Answer 35

the enterohepatic circulation; leads to drug persistence and prolongs the half-life of the drug. This does not go on forever however as every time the drug enters the liver it could be metabolised where it will then be sent off on a different route

Question 36

what does bioavailability mean

Answer 36

proportion of the administered drug that is available within the body to exert its pharmacological effect. This is regarding post-hepatic concentration, the amount that leaves the liver to enter systemic circulation. (the amount of drug that gets into the systemic circulation).

Question 37

what is the apparent volume of distribution

Answer 37

the volume in which a drug appears to be distributed, an indicator of the pattern of distribution. Polar drugs won’t be distributed very far as they are more likely to just remain in the blood. It is a theoretical mathematical concept

Question 38

what is a biological half-life

Answer 38

time taken for the concentration of the drug in the blood/plasma to fall to half its original value

Question 39

what is clearance

Answer 39

the volume of plasma cleared of a drug per unit time. This relates to both the volume of distribution and the rate at which the drug is eliminated. This is incorporating excretion through the bile and the kidneys and all other routes

Question 40

what are first order kinetics of a drug

Answer 40

The rate of elimination of a drug where the amount of drug decreases at a rate that is proportional to the concentration of drug remaining in the body

Question 41

What are zero order kinetics of a drug

Answer 41

A constant amount of drug is removed per unit time

Question 42

What drugs follow first order kinetics

Answer 42

Most drugs

Question 43

An example of a drug that follows zero order kinetics?

Answer 43

Alcohol