ADME 8 Flashcards
DEFINE excretion
Physical removal of drug from body
•Competes against drug absorption
•Terminates biological activity
what does excretion prevent?
accumulation of foreign metabolites/ drugs
what does excretion maintain?
volume and composition of body fluids
Controls acid-base balance
which routes are the major and minor routes of excretion?
major- kidney
minor- bilary/ skin/lung/ ovaliary
define clearance
Measure of the body’s ability to eliminate a drug
what are the barriers in clearance?
cell membranes
is clearance additive?
yes
what is the calculation for clearnace?
Ltotal= Clrenal+ CLhepatic+ CLother
what determines most drugs duration of action?
rate of renal elimination
what are drugs that are excreted 75-100% uncganged?
atenolol, benzylpenicillin, cimetidine, digoxin, frusemide, gentamicin, methotrexate, neostigmine, oxytetracycline
how does passive reabsorption occur?
Lipid soluble compounds move back into blood
Polar and ionised remain in the urine
what does rate of administration equal in celarance?
Rate of ‘administration’ equals rate of elimination
what does the rate of clearance dictate?
Rate of clearance dictates interval of administration
what needs to be known in clearnace?
the volume of distribution/ blood concentrations of drug
what is the calculation for renal clearance?
urinary conc- rate of flow of urine/plasma conc
define clearnace
Describes efficiency of irreversible elimination of drug from body
Useful to plan dosage regimen
what factors could influence half life?
Liver/kidney impairment Pregnancy Urinary pH Drug interactions Age
what is steady state concentration?
Rate entering systemic circulation= rate of elimination
how much of cardiac output does the kidneys receive?
Kidneys receive ~1/5thcardiac output (~650 mL min-1)
how does renal filtration occur?
Occurs by hydrostatic pressure gradient
•Glomeruli filtration ~125 mL min-1(volume independent of drug plasma concentration)•Blood pressure dependant (individual dependant)
do drugs who have a lot of protein bound subsituents filter quicker or slower?
slower
why does passive reabsorption through the distal tubules occur?
to maintain homeostasis
large concentration gradient between drug in tubular lumen and plasma
if urine flow increases, time drug is exposed to reabsorbtive surface decreases- what occurrences could this be of use?
–basis of treatment in some cases of drug overdose–forced diuresis with large volumes of fluids
where does active tubular secretion occur?
Active transport from plasma to urine across proximal renal tubule epithelial cells
how does the active reabsorption of water take place?
–aquaporins–concentrates urine causing concentration gradient
what is the equation for renal excretion?
Renal Excretion : filtration rate + secretion rate –renal reabsorption rate
what is the equation for free plasma concentration?
Free plasma concentration: = Fu x plasma conc
what is the equation for filtration rate?
Filtration rate : = GF x Free plasma conc
what is the equation for secretion rate?
Secretion rate : = Measured excretion rate –filtration rate
why is the reabsorption rate negilible in some cases?
Reabsorption :fu: fi= 0.001:0.999•Reabsorption rate is negligible so not a significant contributor to excretion profile (< 1 mg min-1)
what is the equation for renal clearance?
Renal clearance = excretion rate / plasma drug concentration
what happens if you modify the urinary ph?
Modification of urinary pH in tubules has toxicological implications
–reabsorption in kidney tubules is possible
–unionised drug crossing a biological membrane
what are the benefits of modification of urinary ph?
if ionised cannot be reasborbed in toxic overdoses acidify urine (ammonium chloride) Basify urine (sodium bicarbonate, IV every 3-4 h) shifts equilibrium
what are the two ways which it can be excreted via bile?
Excreted as parent or metabolite
Phase II metabolism aids biliary excretion
what route can large polar molecules be excreted in?
excreted via bile- too large for re-uptake
excreted via feces
where is the possibility for reabsorption after secretion in the bile?
Enterohepatic Recycling
how does Enterohepatic Recycling occur?
Drug conjugates may be cleaved by enzymes in the intestinal micro florato liberate the parent lipid-soluble drug, which may be reabsorbed
what are the other possible routes to excretion
blood/ tears/ sweat/ alveolar/ milk/ saliva
what is differet in a foetus?
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
