Pharmacokinetics 4: Drug Excretion Flashcards
What is drug excretion?
The process whereby an unchanged drug undergoes permanent removal from the body via kidneys or hepatobiliary system.
How is drug elimination different to excretion?
Irreversible removal of the drug + drug lost through biotransformation
Which organs are the main excretory organs? What other organs can be used for excretion?
The kidneys and the liver are the primary excreting organs.
Sweat and tears
Saliva (most is swallowed though)
Breast milk (basic lipophilic drugs)
Hairs, nails, skin minor overall
What kinds of drugs can be excreted in breast milk?
Basic lipophilic drugs (eg cocaine)
What are the main ways for drug to be removed?
Metabolism within the liver and gut wall is the primary route (>75% of drugs)
Renal clearance is less common but also a route (20%)
Bile excretion (4- 5%)
Why are the kidneys such a large site of drug excretion?
They receive a large blood flow (1L/min which is 25% of CO at rest) 10% of this is filtered at the glomerulus.
What percentage of drugs use the kidneys as their primary route of excretion?
25%
Do kidneys remove the parent drug or the metabolite from the blood?
Both (Drugs that are excreted unchanged in urine are called renally cleared drugs)
Examples of renally cleared drugs:
Penicillins
Digoxin
Cephalosporins
Antifungals
Metformin
What drugs are filtered at the glomerulus?
Drugs that are unbound pass through glomerular pores.
Protein bound drugs are inhibited and stay in the blood.
Which drugs are reabsorbed at the proximal tubule?
Mainly small, lipophilic, neutral drugs
How can drugs move into and out of the kidneys?
Glomerular filtration (unbound drugs) Into filtrate
Passive reabsorption out of filtrate
Active transport Into filtrate
Drug excretion depends on these 3 factors.
Where does active transport of drugs into urine take place?
In the proximal tubules
What is GFR among adults?
~120ml/min [180L/day in adults]
How does active transport from the blood into the filtrate take place?
They depend on both SLC and ABC drug transporters.
SLC transporters are located on basolateral membrane.
ABC transporters pump drugs from proximal tubule cells into the urinary lumen.
True or False:
Amount of drug transported from blood to urine by transporters is constant.
True, however, theoretically these transporters can be saturated at higher drug doses.(only drug where this is known to happen is alcohol)
What causes passive reabsorption of drugs back into the blood?
The drugs must be permeant for this to take place. For this reason only small, lipophilic and neutral or nonionised drugs can be reabsorbed.
What determines how much reabsorption takes place?
Reabsorption is proportional to drug concentration in blood.
Drug pKa also matters (CLr may change with varying urine pH)
What happens to proteins bound to plasma?
Only free drug is filtered (bound drug doesn’t)
Free and bound drugs are both actively transported into the urine.
What influences urinary pH?
Diet (high protein diet = acidic urine)
How does pH affect urinary excretion?
Acidic drugs are -ve in alkaline urine = less reabsorption.
Basic drugs in acidic pH = less reabsorption
What is actual renal clearance?
It is indicated by parent drug concentrations in the urine.
Baseline renal clearance is shown by fu x GFR and secretion/reabsorption creates the actual renal clearance.
When is a drug said to be undergoing active secretion?
if RC > fu x GFR
When is a drug said to be undergoing active reabsorption?
if RC < fu x GFR
