ADME 8

Question 1

DEFINE excretion

Answer 1

Physical removal of drug from body
•Competes against drug absorption
•Terminates biological activity

Question 2

what does excretion prevent?

Answer 2

accumulation of foreign metabolites/ drugs

Question 3

what does excretion maintain?

Answer 3

volume and composition of body fluids

Controls acid-base balance

Question 4

which routes are the major and minor routes of excretion?

Answer 4

major- kidney

minor- bilary/ skin/lung/ ovaliary

Question 5

define clearance

Answer 5

Measure of the body’s ability to eliminate a drug

Question 6

what are the barriers in clearance?

Answer 6

cell membranes

Question 7

is clearance additive?

Answer 7

yes

Question 8

what is the calculation for clearnace?

Answer 8

Ltotal= Clrenal+ CLhepatic+ CLother

Question 9

what determines most drugs duration of action?

Answer 9

rate of renal elimination

Question 10

what are drugs that are excreted 75-100% uncganged?

Answer 10

atenolol, benzylpenicillin, cimetidine, digoxin, frusemide, gentamicin, methotrexate, neostigmine, oxytetracycline

Question 11

how does passive reabsorption occur?

Answer 11

Lipid soluble compounds move back into blood

Polar and ionised remain in the urine

Question 12

what does rate of administration equal in celarance?

Answer 12

Rate of ‘administration’ equals rate of elimination

Question 13

what does the rate of clearance dictate?

Answer 13

Rate of clearance dictates interval of administration

Question 14

what needs to be known in clearnace?

Answer 14

the volume of distribution/ blood concentrations of drug

Question 15

what is the calculation for renal clearance?

Answer 15

urinary conc- rate of flow of urine/plasma conc

Question 16

define clearnace

Answer 16

Describes efficiency of irreversible elimination of drug from body
Useful to plan dosage regimen

Question 17

what factors could influence half life?

Answer 17

Liver/kidney impairment
Pregnancy
Urinary pH
Drug interactions
Age

Question 18

what is steady state concentration?

Answer 18

Rate entering systemic circulation= rate of elimination

Question 19

how much of cardiac output does the kidneys receive?

Answer 19

Kidneys receive ~1/5thcardiac output (~650 mL min-1)

Question 20

how does renal filtration occur?

Answer 20

Occurs by hydrostatic pressure gradient
•Glomeruli filtration ~125 mL min-1(volume independent of drug plasma concentration)•Blood pressure dependant (individual dependant)

Question 21

do drugs who have a lot of protein bound subsituents filter quicker or slower?

Answer 21

slower

Question 22

why does passive reabsorption through the distal tubules occur?

Answer 22

to maintain homeostasis

large concentration gradient between drug in tubular lumen and plasma

Question 23

if urine flow increases, time drug is exposed to reabsorbtive surface decreases- what occurrences could this be of use?

Answer 23

–basis of treatment in some cases of drug overdose–forced diuresis with large volumes of fluids

Question 24

where does active tubular secretion occur?

Answer 24

Active transport from plasma to urine across proximal renal tubule epithelial cells

Question 25

how does the active reabsorption of water take place?

Answer 25

–aquaporins–concentrates urine causing concentration gradient

Question 26

what is the equation for renal excretion?

Answer 26

Renal Excretion : filtration rate + secretion rate –renal reabsorption rate

Question 27

what is the equation for free plasma concentration?

Answer 27

Free plasma concentration: = Fu x plasma conc

Question 28

what is the equation for filtration rate?

Answer 28

Filtration rate : = GF x Free plasma conc

Question 29

what is the equation for secretion rate?

Answer 29

Secretion rate : = Measured excretion rate –filtration rate

Question 30

why is the reabsorption rate negilible in some cases?

Answer 30

Reabsorption :fu: fi= 0.001:0.999•Reabsorption rate is negligible so not a significant contributor to excretion profile (< 1 mg min-1)

Question 31

what is the equation for renal clearance?

Answer 31

Renal clearance = excretion rate / plasma drug concentration

Question 32

what happens if you modify the urinary ph?

Answer 32

Modification of urinary pH in tubules has toxicological implications –reabsorption in kidney tubules is possible –unionised drug crossing a biological membrane

Question 33

what are the benefits of modification of urinary ph?

Answer 33

``` if ionised cannot be reasborbed in toxic overdoses acidify urine (ammonium chloride) Basify urine (sodium bicarbonate, IV every 3-4 h) shifts equilibrium ```

Question 34

what are the two ways which it can be excreted via bile?

Answer 34

Excreted as parent or metabolite | Phase II metabolism aids biliary excretion

Question 35

what route can large polar molecules be excreted in?

Answer 35

excreted via bile- too large for re-uptake | excreted via feces

Question 36

where is the possibility for reabsorption after secretion in the bile?

Answer 36

Enterohepatic Recycling

Question 37

how does Enterohepatic Recycling occur?

Answer 37

Drug conjugates may be cleaved by enzymes in the intestinal micro florato liberate the parent lipid-soluble drug, which may be reabsorbed

Question 38

what are the other possible routes to excretion

Answer 38

blood/ tears/ sweat/ alveolar/ milk/ saliva

Question 39

what is differet in a foetus?

Answer 39

The blood-brain-barrier of an infant is not often complete until 1-2 years of age •A foetus–fewer plasma proteins (more available drug for absorption to CNS)–has a greater proportion of blood flow to the brain–has lower levels of metabolic enzymes–has slower drug excretion•direct toxic effect