week 2

Question 1

list the four stages of drug disposition

Answer 1

1. Absorption
2. Distribution (plasma/tissue distribution)
3. Metabolise (biotransformation)
4. Excretion = out of body (different to elimination which means not active anymore)

Question 2

list the three basic movements of substances across a cell membrane

Answer 2

1. passive movement

• paracellular transport
• diffusion
• facilitate diffusion (carrier)

2. active transport

• movement against gradient
• uses carriers & energy

3. pinocytosis

• fluid endocytosis
• also internalise small particles suspended in extracellular fluids

Question 3

define SLC

Answer 3

= solute carriers co-transporter = use gradient not energy to co-transport solutes e.g. inorganic ions, amino acids, lipids. Sugars, neurotransmitters, drugs

Question 4

define absorption of drug

Answer 4

= movement from site of administration into plasma

Question 5

factors that effect absorption of drug x9

Answer 5

1. lipid solubility (molecular weight & structure pKa)
2. surface area
3. gut content
4. GI transit time (food, dioheara, vomiting)
5. blood flow at site of administration
6. drug interaction
7. age
8. health status
9. genetic polymorphisms

Question 6

what type of molecules can freely cross a membrane

Answer 6

molecules in which electrons are uniformly distributed = unionised

Question 7

if the pKa of acetic acid is 5 and the pH of the environment is 1 is the environment basic or acidic

Answer 7

protonated = acidic - drug can cross the membrane

Question 8

if the pKa of acetic acid is 5 and the pH of the environment is 8 is the environment acidic or basic

Answer 8

deprotonated = basic - drug can’t cross membrane

Question 9

if the drug is more basic is it able to travel through the membrane

Answer 9

no

Question 10

why do weak acids get trapped in the cell

Answer 10

because it means they usually have a pKa of around 4.4 meaning the environment pH is usually higher at around 7 which means they are trapped because it is in the ionised form as a basic acids

Question 11

the higher the pH

Answer 11

facilitates dissociation

Question 12

the lower the pH

Answer 12

reduces dissociation

Question 13

what does the Henderson-Hasselbalch equation allow us to predict

Answer 13

we can calculate the unionised amount of the drug which means we can predict the absorption of the drug, and where the drug can be trapped depending on the pH of the environment

Question 14

routes of administration

Answer 14

o	Oral 
o	Sublingual 
o	Rectal 
o	Application to other epithelial surfaces (e.g., skin, cornea & vagina)
o	Inhalation (pulmonary)
o	Injection 
o	Subcutaneous (SC) – insulin 
o	Intramuscular (IM) – covid 
o	Intravenous (IV)
o	Intra-arterial 
o	Intrathecal & intravitreal

Question 15

define parameter

Answer 15

a measurable factor forming one of a set that defines a system or sets the conditions of its operation

Question 16

what are the parameters in pharmacokinetics

Answer 16

1. C max
2. T max
3. peak absorption phase
4. peak elimination phase
5. above therapeutic range
6. bioavailability
7. volume of distribution

Question 17

define area under a curve

Answer 17

provides a measure of drug exposure

Question 18

define bioavailability

Answer 18

important parameter to inform the fraction of the drug that has reached the systemic circulation = blood plasma = NOT THE ACTUAL SITE = drug unaltered from entering the site of administration

Question 19

if 100% of the does of drug enters the systemic circulation the bioavailability is

Answer 19

1.0

Question 20

the fraction is equal to

Answer 20

the quantity of drug reaching the systemic circulation divided by the quantity of drug administered

Question 21

factors that may affect drug bioavailability

Answer 21

1. first-pass metabolism = broken down/altered before destination, enzymes released from bacteria could break down drugs
2. neglects rate of absorption
3. gastic pH
4. intestinal motility

Question 22

how can absorption characteristics change even though the same drug is administrated

Answer 22

the formation of the drug e.g. oral or intravenous

Question 23

factors that affect drug distribution x9

Answer 23

1. large drug
2. polar drug
3. drug enriched in fat
4. permeability across tissue barriers
5. binding within compartments
6. pH partition
7. fat: water partition
8. blood flow to the tissue = takes more to get to toes
9. protein binding

Question 24

how much of our body is water (percentage)

Answer 24

50-70%

Question 25

the four main compartments

Answer 25

1. plasma
2. interstitual fluid
3. intracellular fluid
4. transcellular fluid

Question 26

effect of drug binding to protein

Answer 26

• Only the free or unbound drug fraction exerts pharmacological effects meaning if someone is low on the protein that binds then the dose could be too much and cause toxicity
• If bound to protein more likely to stay in the blood stream

Question 27

what happens if too much drug compared to protein

Answer 27

not enough protein to bind to the drug meaning more drug is active meaning could cause toxicity

Question 28

define volume of distribution

Answer 28

= the volume of fluid into which a drug appears to be distributed or diluted

Question 29

the equation for Vd

Answer 29

Vd = amount of drug in the body (mg) divided by the plasma concentration of drug (mg/L)

Question 30

high Vd means

Answer 30

more of the drug is in the tissues

Question 31

factors affecting Vd

Answer 31

1. age
2. gender
3. body composition
4. presence of disease

Question 32

apparent plasma volume

Answer 32

about 0.5L/kg body weight (approx. 4L)

Question 33

apparent the extracellular volume

Answer 33

about 0.2L/kg

Question 34

apparent total body water

Answer 34

about 0.55 L/kg (approx. 42L)

Question 35

most drugs are designed to be…(pH level)

Answer 35

weak acids & bases

Question 36

is a drug that is protonated or deprotonated easier to cross a membrane ?

Answer 36

protonated

Question 37

when the pH is lower then the pKa of the compound does that make the environment acidic or basic ?

Answer 37

acidic

Question 38

pKa define

Answer 38

the pH at which 50% of the drug is in its ionised form

Question 39

if the drug is an acid and protonated (due to the environment) then the acid is …

Answer 39

unionised

Question 40

example of drug diffusing from gastrointestinal tract

Answer 40

if the drug is a weak acid (4.4), the gastic juice pH is high (1.2), thus, the drug can cross the membrane. however, once the drug is in the plasma, due to the low plasma pH (7.4) the drug becomes deprotonated and ionised meaning it cannot cross back, meaning the drug is trapped in plasma. this is good because then it has to then be absorbed into tissue to have effect.

Question 41

define absorption

Answer 41

refers to the ability for drug to cross the gut wall into the portal vein

Question 42

difference between poor oral availability and high first pass metabolism

Answer 42

poor oral availability - the drug isn’t absorbed from the gastrointestinal tract into the portal vein. instead it keeps going through intestines and is excreted

high first pass metabolism - the drug is absorbed into the portal vein from the gastrointestinal tract but when goes into the liver a high amount is metabolised and less leaves the liver = affects bioavailability

Question 43

vd unit

Answer 43

L