ELimination Flashcards
What is Elimination? Where does elimination take place for IV administration?
The removal of a drug molecule from the body without chemical modification
Following i.v administration;
No metabolism takes place
Elimination is 100% via renal excretion
What are the three elimination processes that occur via the kidney?
The kidney uses three mechanisms of drug excretion: glomerular filtration, active secretion through the proximal tubules, or distal tubule reabsorption.
What is Glomerular Filtration? Which molecules are filtered and what type of transport is used?
The glomerular filtration rate (GFR) shows how well the kidneys are filtering
Passive process (Pressure driven)
20% of plasma volume is filtered
Small molecules - Yes
Large molecules - No
Most proteins not filtered. Drugs which are extensively protein bound will also not be filtered.
What is Active Secretion?
The majority of drugs do not enter the kidney tubule by glomerular filtration but do so by tubule secretion. This is an active process since drugs are carried against a favourable chemical gradient from the capillary network into the tubule.
Energy requiring
Can generate positive concentration
gradients
Two separate mechanisms for acids & bases
Saturable
Possible interactions
Give example of active secretion acidic drugs?
Furosemide (diuretic) , Penicillins, Probenecid (for gout)
Penicillin and Probenecid share same mechanism
Probenecid competes with penicillins
Penicillin clearance reduced
Give examples of active secretion bases?
Quinine, Quaternary ammonium salts
What molecules are reabsorbed and what molecules can be efficiently excreted by the kidneys?
99% of water is reabsorbed
Lipid soluble drugs reabsorbed along with the water.
Only very water soluble molecules can
be efficiently excreted by the kidneys.
What is ion trapping?
ion trapping is the build-up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane. This results in basic chemicals accumulating in acidic bodily fluids such as the cytosol, and acidic chemicals accumulating in basic fluids.
What is given when a barbiturate overdose?
Urine pH varies (4.5 - 8.0). Consider a barbiturate overdose. Sodium bicarbonate may be given to make the urine alkaline
Barbiturate moves into urine - eliminated from body
What is High Renal Clearance?
If renal clearance is greater than G.F.R. then there must be active secretion
Max possible renal clearance is approx.
650 ml/min (All plasma cleared)
e.g. Aminohippuric acid
What is Low renal clearance?
If clearance is much less than G.F.R. then either:
Not filtered or
Extensively reabsorbed
e.g. antipyrine, thiopental
What is creatine and creatine clearance?
Creatinine is a waste product formed continuously by muscle.
Filtered by kidneys
Almost no active secretion
Almost no reabsorption
Creatine clearance approx equals filtration rate (G.F.R.)
Creatinine clearance used as an estimate of G.F.R.
Why are creatinine clearance and GFR important in ADME?
The clearances of many renally excreted drugs are closely linked to GFR
e.g. The clearance of gentamicin approximately equals GFR and therefore also approximates to creatinine clearance.
When calculating a dosage regime we can assume that gentamicin clearance will equal creatinine clearance
What are Factors influencing serum creatinine concentration
1) Creatinine production rate
depends upon muscle mass, which in turn depends upon:
Body weight
Age (% muscle declines with age)
Gender (Men have higher % muscle than women)
2) Creatinine clearance rate
What are routes of excretion?
Biliary
Pulmonary
Mammary
Salivary
First Pass Metabolism
