Drug absorption & distribution (L5)

Question 1

what is pharmacokinetics (PK)?

Answer 1

what the body does to the drug

ADME 
• absorption 
• distribution 
• metabolism 
• excretion

Question 2

what is pharmacodynamics (PD)?

Answer 2

what the drug does to the body

time course and mechanism of therapeutic effects

how the drug works

Question 3

what happens in absorption?

Answer 3

transfer of an exogenous compound from site of administration into the systemic circulation

• usually needs to pass cell membranes
• passive diffusion doen conc gradient
• active transport

Question 4

what are the 3 types of administration routes for a drug?

Answer 4

IV
oral
dermal

Question 5

how do you decide which route is best?

Answer 5

• physiochemical properties
• therapeutic aims
• patient preferences
• pharmacokinetic properties

Question 6

when is parental delivery needed?

Answer 6

• when drug is poorly absorbed
• drug is unstable or metabolised in GI tract
• rapid onset of action is needed
• high dose control is needed

Question 7

parental delivery includes…

Answer 7

intravenous - bolus or infusion

intramuscular - injected dose is stored in the muscle and diffuses over time

subcutaneous - bolus or infusion

Question 8

how is the small intestine involved in absorption?

Answer 8

site of absorption of most orally administered exogenous compounds

large, highly permeable SA
excellent blood supply

enterocytes of epithelium contain metabolic enzymes and transporters

Question 9

what is first pass metabolism?

Answer 9

a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation

Question 10

what are other absorption routes?

Answer 10

• sublingual
• inhalation
• rectal
• vaginal
• transdermal

Question 11

absorption in the sublingual route

Answer 11

under the tongue

films and sprays

excellent network of capillaries under the tongue - drug delivered directly into the blood stream

Question 12

absorption by inhalation

Answer 12

inhalation of powders, gases and suspensions

excellent network of capillaries under the tongue - drug delivered directly into the blood stream

Question 13

absorption in the rectal route

Answer 13

suppositories and enemas

useful for treating illnesses where vomiting is a symptom

good blood supply

Question 14

absorption in the vaginal route

Answer 14

gels, pessaries and rings

can ensure local drug efficacy with reduced systemic side effects

good blood supply

pH variances through the menstruation cycle may affect absorption

Question 15

absorption in the transdermal route

Answer 15

even highly lipid soluble chemicals are slow to enter the bloodstream through the skin

Question 16

what factors affect absorption via the skin?

Answer 16

• size of drug molecule
• membrane permeability of drug delivery system
• skin hydration
• pKa of drug
• drug metabolism by skin flora
• lipid solubility

Question 17

what are class I drugs?

Answer 17

high permeability and high solubility

often these drugs are absorbed faster than excreted due to their high solubility

e.g. propranolol

Question 18

what are class II drugs?

Answer 18

high permeability and low solubility

bioavailability and distribution is limited by the time taken for the drug to dissolve

e.g. naproxen

Question 19

what are class III drugs?

Answer 19

low permeability and high solubility

a very solvent drug that is limited by its ability to pass through membranes

e.g. ranitidine

Question 20

what are class IV drugs?

Answer 20

low permeability and low solubility

drugs with very low bioavailability - not good at crossing membranes or being dissolved

e.g. paclitaxel

Question 21

what factors affect absorption?

Answer 21

• blood flow
• absorptive SA
• contact time at absorptive surface
• gastric emptying

Question 22

what is Cmax?

Answer 22

maximum concentration of compound after dosing

Question 23

what is Tmax?

Answer 23

time taken to reach maximum drug conc

Question 24

what is the area under the curve (AUC)?

Answer 24

considered a measure of systemic exposure

Question 25

what is bioavailability (F)?

Answer 25

the extent of absorption - how much is available to have an effect on the body

comparison using IV dosing

Question 26

what do you need to know to work out bioavailability?

Answer 26

• how much exposure using IV route
• how much exposure using oral route
• IV dose administered
• oral dose administered

Question 27

equation for bioavailability

Answer 27

F = (AUCoral/AUCiv) x (DOSEiv/DOSEoral)

lower bioavailability means more of the oral dose is lost

Question 28

how is IV and oral bioavailability different?

Answer 28

IV administration - whole dose goes straight into the bloodstream

oral administration - some drug lost to first pass metabolism, lower overall exposure (lower AUC)