L38 - Drug Elimination - Excretion 1 Flashcards
What is eliimation?
Irreversibe loss of drug by excretion/metabolism
What is excretion?
Irreversible loss of chemically unchanged drug (kidneys, urine and bile, sweat, saliva and air)
What is metabolism?
Conversion of the drug into a different chemical species (liver, metabolised in GI wall, blood, skin, kidney)
What is renal clearance defined as? (Proportionality)
Proportionality factor that relates the renal elimination rate of a drug with the drug concentration in blood (plasma)
What is the renal clearance defined as (volume)?
Volume of fluid that is completely clearaed of drug by the kidneys per unit time
What is the eqn for rate of renal elimination?
Rate of renal elimination = renal clearance x Cdrug
What does renal clearance measures?
Loss of drug across the kidney
What can renal clearance be defined as?
- ratio between elimination rate by kidney and the incoming concentration
- volume of blood enetering the kidney from which all the drug is remover per unit time
What is the renal clearance equation?
ClR = rate elimination / Centering
= Qr x E
When is renal extraction rate high and low?
- high - E => 0.7
- low - E =<0.3
What are the main organs invovled in renal excretion?
- kidneys
- other sites - bile, sweat, saliva, milk, air
What are the 3 processes contributing to renal excretion?
- glomerular filtration
- active tubular secretion
- passive and active reabsorption
What is renal excretion like in healthy subjects?
Less variable than hepatic metabolism
What are the 3 main reasons for variability in the renal excretion of a drug?
- renal disease
- age - decrease in renal function
- drug interactions
What is blood flow like in the kidneys?
~1.2 L/min of blood (72L/h)
What are the roles of kidneys?
- water and electrolyte balance
- hormone secretion
- blood pressure
- removal (metabois waste, foreign substances)
What are the parts of the nepthron?
- glomerulus
- PCT
- loop of henle
- DCT
- collecting tubule
What do nephrons work as?
- filters
- to converse useful materials
- to eliminate waste, toxic, foreign materials
- regulate water loss
What is glomerular filtration like?
- 10% of blood supplt filtered (unidirectional, hydraulic pressure exerted by arterial blood)
- 20-25% cardiac input (120mL/min filtered)
What happens to molecules dissolved in blood (plasma)?
- ionised and non ionised molecules filteres
- MW <2,000 filtered easy. >20,000 filtration falls
- no albumin found in ultra filtrate, only unbound drugs filtered
What are the 2 types of reabsorption in tubular reabsorption?
- passive
- active
What is passive reabsorption like?
- 99% filtered water reabsorbed
- driving force for solutes passive reabsorption
- effect of ionisation, lipophilia
What is active reabsorption like?
- mediated by transportes at the PCT
- vitamins B and C, glucose, a/a, some drugs
How does drug reabsorption affect renal clearance?
Drug reabsorption decreases the renal clearance of a drug
What are the steps in passive reabsorption?
- plasma filtered, free Cdrug is the same in plasma and filtrate
- ~99% water reabsorbed, Cdrug increases in filtrate
- drug conc establised across membrane = passive diffusion of drug back into body
What is tubular renal secretion mediated by?
Active process mediated by carriers
What are carriers like in tubular renal secretion?
- not specific
- anions secreting systems (acids)
- cation secreting systems (bases)
What are processes like in tubular renal secretion?
- highly efficient and fast
- completely removed from drug even if bound
- dependent on renal blood flow
What are carrier systems like?
- interactions - probenecid competes with penicillin for same carrier = decreases active secretion and CI renal of the drug
- transportes beomce saturated (non linear kinetics)
What do each process do in renal excretion?
- add drug to lumen, increase renal elim - glomerular filtration, tubular active secretion
- moves drug back to blood, decreases renal elim - tubular reabsorption
What do the 3 mechs affect renal excretion?
- glomerulal filtration - inc ClR
- reabsorption - dec ClR
- secretion - inc ClR
What is the eqn for ClR using the 3 mechs?
ClR = Clfiltration + Clsecretion - Clreabsorption
What drugs are considered for ClR?
- not bound in blood
- only eliminted by glomerular filtration
What is creatinine?
- waste product procuded by muscle metabolism
- completely unbound in plasma
What does creatinine conc in serum depend on?
- rate in - muscle metabolism (age,sec)
- rate out - renal excretion by glomerular filtration
What is creatinine production rate like in eq?
Creatinine production rate = Clcreatinine x Ccretinine,serum
Eq = dec x inc
How is creatinine used to look into renal failure?
As the kidneys fail, creatinine decreases
What is the eqn for ClR when GFR considered?
ClR = funbound x GFR
= funbound x Clcr
