Drug absorption and Bioavaliability

Question 1

is intramuscular intravascular or extravascular

Answer 1

extravascular

Question 2

for drugs administered extravacularily, do they act systemically or locally?

Answer 2

systemically

Question 3

if drugs are intended for local use, what can be a concern?

Answer 3

systemic absorption

Question 4

define bioavailability?

Answer 4

refers to the extent of absorption of intact drug. Fraction of an extravascularly administered dose that reaches the systemic circulation intact

Question 5

what is bioavaliability important for?

Answer 5

knowing the dosage of drug, if poor bioavailability, you will increase the dose

Question 6

when is absolute bioavailability used?

Answer 6

with reference to an intravenous dose- if you give it IV, you have 100% absorption

Question 7

what is relative bioavailability

Answer 7

comparison of the bioavailability between formulations of a drug given either by the same or different routes of administration
can then choose the drug with the highest bioavailability

Question 8

what is bioequivalence?

Answer 8

formulations containing the same dose of same chemical entity, generally in the same dosage form, intended to be interchangeable

Comparing formulations that have the same dose (and dosage forms) and see if they are equivalent and can be used interchangeably

Question 9

how can we see differences in bioequivalence?

Answer 9

looking at the concentration time profile

Question 10

if 2 bioequivalent drugs have a similar plasma concentration time profile what does this mean?

Answer 10

less likely to cause clinically relevant differences in therapeutic and adverse effects

Question 11

rate limiting steps for oral absorption?

Answer 11

Disintegration time and dissolution rate 
Gastric emptying and intestinal transit 
Movement through membranes 
o	Perfusion 
o	Permeability limitations 
First-pass metabolism in the gut/liver

Question 12

factors affecting intestinal absorption?

Answer 12

surface area
blood flow
permeability

Question 13

why does gastric emptying control

Answer 13

emptying controls the delivery of drug to small intestine and affects the rate of absorption [Some of the drug can be absorbed in the stomach but that is a minor contributor]

Question 14

factors affecting gastric emptying

Answer 14

age
coadministration with another drug
food

Question 15

effect of anticholinergic drugs on gastric emptying

Answer 15

anticholinergic react the smooth muscles in the stomach, so gastric emptying is delayed

Question 16

if you give a drug on a fasted stomach the transit time is….

Answer 16

very short so will be quickly delivered to the SI

fast delivery to the upper SI

Question 17

does food effect small intestine transit time?

Answer 17

no not really

Question 18

does particle size make a difference in the SI

Answer 18

no difference between particle sizes in the SI

Question 19

enteric coated should be given on a what stomach? why?

Answer 19

FASTED
so they reach the SI as fast as possible to avoid the possibility that the EC will be damaged by sitting in the stomach [omeprazole, erythromycin]

Question 20

poorly soluble drugs should be given on a what stomach? why?

Answer 20

FED
food deliberately delaying gastric emptying which will increase the time for dissolution of the molecule allowing more time for the molecule to be absorbed

Question 21

risks associated with raised BMI

Answer 21

↑ Cardiovascular disease
↑ Diabetes
↑ Muscoskeletal disorders
↑ Some forms of cancer

Question 22

what is gastric bypass

Answer 22

reduction in surface area of stomach, pH changes. Connected to distal region of the small intestine

Question 23

does gastric bypass change pH

Answer 23

yes

Question 24

how is drug absorption affected with gastric bypass?

Answer 24

Bypass of main areas of drug absorption – e.g., duodenum and the jejunum (~75cm bypassed) as the new stomach is connected to the further region of the SI

Question 25

how does coeliac disease effect drug absorption?

Answer 25

Expression of intestinal CYP3A reduced on average to 15% of expression levels in healthy subjects

Question 26

does coeliac disease effect first pass and bioavailability

Answer 26

yes

Question 27

how does liver cirrhosis effect drug absorption?

Answer 27

intestinal enzymes may be affected

Question 28

effect of liver cirrhosis on F and first pass?

Answer 28

reduced F

Reduced activity of many metabolic enzymes, extent depends on severity of disease

Question 29

effect of chronic kidney disease on stomach?

Answer 29

increased gastric emptying time

increased pH

Question 30

chronic kidney disease effects on metabolism and elimination

Answer 30

reduced renal elimination

expression of CYP450 enzymes changed for metabolism