Lecture 2 - Translocation of drugs

Question 1

What are the two fundamental processes that determine drug concentrations in different body compartments?

Answer 1

-Translocation of drug molecules
- chemical transformation

Question 2

what is translocation of drugs? 2 types transfer

Answer 2

drug movement around the body
- bulk flow
- diffusional transfer

Question 3

What is bulk flow transfer? (blood stream)

Answer 3

chemical nature of drug has no effect

Question 4

what is diffusional transfer? (molecule by molecule over short distances)

Answer 4

• hydrophobic diffusion barrier
• aqueous diffusion

differes markebly between drug with different chemical properties

Question 5

theory of a compartmentalised body?

Answer 5

‘Body made of inter-connected compartments separated by cell
membranes’

Question 6

what does the ability of drugs and other chemicals to move between these
compartments depend on?

Answer 6

selectivity of the membranes and the
chemical properties of the drug

Question 7

What type of membrane does the epithelial barrier have in the GI and kidneys ?

Answer 7

single layer

Question 8

what is a vascular endothelium ?

Answer 8

non selective mostly
- acts as a filter

Question 9

what are the gaps between cells filled with in VE ?

Answer 9

protein matrix - tightly packed
- acts as MW filters

Question 10

Large _____ allow drugs to exchange
____ between _____ and _______ in the
liver

Answer 10

fenestrations
freely
blood
interstitium

Question 11

In liver and spleen, e__othelium is
______

Answer 11

end
discontinuous

Question 12

_____ junctions in CNS and placenta

Answer 12

Tight junctions in CNS and placenta
- only way chemicals go through is lipid soluble

Question 13

Give ways drug can transverse across cell membrane

Answer 13

• diffuse direct through the lipid
• diff through aqueous pores
• combination with transmembrane carrier protein
• pinocytosis (for macromolecuels e.g. insulin)

Question 14

which ways are important for drug pharmacokinetics across membranes?

Answer 14

• diffusing direct through the lipid
• combination with a transmembrane carrier protein
• maybe pinocytosis

Question 15

Describe diffusion through lipid

Answer 15

• non-polar substances dissolve readily in non-polar solvents - cell membranes are lipid - rich environments
• nonpolar substances can penetrate cell membranes very freely (permable)

Question 16

what is the permability coefficient (P) determined by?

Answer 16

1. number of molecules crossing the membrame per unit area in unit time (J)
2. concentration difference across the membrane (change C)

• J= P difference C

Question 17

____ correlation between lipid solubility and permeability of cell membrane to different substances

Answer 17

Close

Question 18

what can be predicted from measuring / predicting lipability?

Answer 18

-rate of absorbion from gut
- penetration into brain and other tissues
- extent of renal elimination

Question 19

many drugs are either _____ acids or ____ bases

Answer 19

weak

Question 20

Many drugs are either ____ acids or ____ bases
They exist in both ____ and ____ forms.
The ____ form is much less able to penetrate cell membranes

Answer 20

weak
inionsed
unionised
ionised

Question 21

Ratio of Charged Drug/Uncharged Drug concns is determined by the __ of the compartment

Answer 21

pH

Question 22

For many drugs the _____ species is sufficiently lipid
soluble (except e.g. aminoglycosides)

Answer 22

uncharged

Question 23

which has a greater surface area for absorption … sml intes vs stomach?

Answer 23

Small intestine

Question 24

what is aspirin absorption increased by?

Answer 24

metoclopramide

Question 25

what is aspirin absorption decreased by?

Answer 25

propantheline

Question 26

Urinary acidification

Answer 26

^ extretion of weak bases v excretion of weak acids

Question 27

Urinary alkalinisation

Answer 27

v excretion of weak bases ^ excretion of weak acids

Question 28

What does increased plasma pH cause?

Answer 28

extraction of weakly acidic drugs from CNS into plasma

Question 29

what does decreased plasma pH cause ?

Answer 29

weakly acidic drugs to accumulate in the CNS

Question 30

if we increase plasma pH - weak _____ are ___

Answer 30

acids charged

Question 31

What increased excretion of aspirin?

Answer 31

urinary alkalinsation

Question 32

Passive transport::

Answer 32

move molecules in the direction of electrochemical gradient (facilitated diffusion)

Question 33

Active transport:

Answer 33

Movement against an electrochemical gradient, coupled to an energy source by: Direct use of ATP or electrochemical gradient of another species (e.g. Na+) (active transport)

Question 34

Carrier-mediated transport is:

Answer 34

* Saturable * Can be inhibited (competitive inhibition) Carrier-mediated transport

Question 35

higher exposure of Cisplatin results in distructrion of what incracellular thing?

Answer 35

Mitochondria >> proximal tubular cell death

Question 36

Levodopa 'hitches a ride' on which system?

Answer 36

carrier responsible for phenylalanine (L-amino acid transporter) - blood to brain

Question 37

Where is iron absorbed ?

Answer 37

jejunum (sml intest) - using a specific carrier system

Question 38

what does calcium absorption depend on and where does it activate a specific transporter ?

Answer 38

calcium absorption depends on vitamin D vitamin D helps activate transporter in intestine to absorb calcium

Question 39

what are other factors affecting drug pharmacokinetics?

Answer 39

- binding to plasma protein - partition into body fat and other tissues

Question 40

what percentage of H2O and solutes are reabsorbed in the proximal tubule?

Answer 40

70%

Question 41

Function of distal tubule collecting duct ?

Answer 41

control of Na and h2o balance

Question 42

Function of loop of henle?

Answer 42

urinary concentration

Question 43

Function of glomerulus ?

Answer 43

renal blood flow filtration

Question 44

how many L is filtered a day in nephron ?

Answer 44

180

Question 45

What happens at normal pH with salicylate?

Answer 45

a proportion of salicylate is unionised -- can be absorbed back into the SYSTEMIC circulation in the NEPHRON

Question 46

what happens when urine is alkaline with salicylate?

Answer 46

salicylate is charged --- reabsorption is much more reduced

Question 47

why is cisplatin nephrotoxic to certain individuals?

Answer 47

because - efficiently taken up into proximal tubule but - rate of secretion into urine is lower

Question 48

what is Fanconi syndrome

Answer 48

organic solutes lost to urine increased Na loss increased H2O

Question 49

Cisplatin enters cells using a specific transporter. If you block this transporter with a non-toxic blocker, cisplatin can't get into the kidney’s proximal tubule cells, preventing it from building up and causing kidney damage.