pharmacodynamics and pharmacokinetics

Question 1

examples of ways drugs can reach their target (3)

Answer 1

passively diffuse through the phospholipid bilayer of cells (lipid soluble); drug mimics natural protein and is actively transported (e.g. levodopa); via ion channels (small polar molecules e.g. Li+)

Question 2

how are most drugs generally transported in the body

Answer 2

carrier-mediated transport

Question 3

what can affect the ionisation of a drug (and thus its diffusability)

Answer 3

Ka of the drug: pH of the body fluid (favours ionisation?)

Question 4

what is given to treat an aspirin overdose

Answer 4

NaHCO3 - increases the pH resulting in ionisation of aspirin and thus it entering the urine and being excreted

Question 5

for what kind of drugs is an oral dose almost as good as IV and why

Answer 5

lipid soluble - they are non-polar molecules and so can easily pass through cell membranes to their target rather than relying on

Question 6

why is heparin safe in pregnancy

Answer 6

a very polar molecule and so cannot cross the placenta

Question 7

what is the purpose of the blood brain barrier (4)

Answer 7

protect the brain from harmful substances; allow nutrient through; tight capillary endothelia junctions; enzyme barrier

Question 8

ways drugs can be eliminated (5)

Answer 8

urine; faeces; milk; sweat; expired air

Question 9

what does zero order kinetics of a drug indicate

Answer 9

there is a limited capacity of the body to process the drug; as the dose rises above a certain level, metabolic processes cannot cope; dose increase results in sudden toxicity

Question 10

what happens if the breakdown enzyme is saturated

Answer 10

drug cannot be broken down any fast - increasing toxicity (e.g. w alcohol, will get drunk faster after enzyme saturation)

Question 11

what is bioavailability

Answer 11

the proportion of the drug that passes into the systemic circulation after administration

Question 12

what can affect the bioavailability of oral drugs

Answer 12

absorption in GI; loss in faeces; breakdown by gastric acid; liver metabolism

Question 13

what is used to calculate oral bioavailability

Answer 13

amount in circulation after oral dose; amount in circulation after IV dose

Question 14

how can bioavailability be improved (3 + examples)

Answer 14

change in formulation - enteric coated capsules to stop gastric acid degradation;
route - sublingual GTN avoids liver metabolism;
inhibitors - peripheral dopa decarboxylase inhibitor stops levodopa being broken down before it can reach the brain

Question 15

what is apparent volume distribution and what does it indicate

Answer 15

calculation of amount of drug in plasma after being taken up; high V indicated the drug mast have gone elsewhere e.g. fat; low V indicates drug is strongly bound to plasma proteins and not tissues

Question 16

what is clearance

Answer 16

elimination of drug from plasma - the amount of plasma totally cleared of drug

Question 17

what is half-life

Answer 17

the time taken for drug concentration to fall by half its initial value

Question 18

2 main half life determinants

Answer 18

clearance; volume of distribution (i.e. amount of drug available in plasma for kidney/liver to excrete)

Question 19

what is steady state

Answer 19

when a drug is given at a constant rate allowing the plasma conc to plateau; usually after 5 half lives

Question 20

what should be done if a drug has a short half life (to increase - 4)

Answer 20

give a larger dose frequently; inhibit clearance; reduce movement of to plasma (e.g. using adrenaline which promotes vasoconstriction so drug remains local); modify formulation (e.g. sustained release tablets)

Question 21

what is the most important factor in determining dosage regimen?

Answer 21

half life

Question 22

why might stopping a drug not stop its adverse affects

Answer 22

it has a long half life and high volume distribution meaning that it is stored in the tissue even after it has stopped being given