5. Pharmacokinetics 3 Flashcards
What is drug excretion?
Which are the main organs involved?
Where else can they be excreted?
Drug Excretion
- Involves the excretion (elimination) of both active drug and drug metabolites from the body
- The kidneys are the main organs involved in the excretion of active drug and drug metabolites from the body
- Drugs and their metabolites may also be excreted by the gastrointestinal tract (faeces) and to a far lesser extent by some other organs e.g. the lungs (some general anaesthetics)
What is Glomerular Filtration?
What percentage of cardiac output is received by the kidneys?
How much filtrate is made each day?
Glomerular Filtration = the process by which the kidneys filter the blood and remove waste products and fluid
- The kidneys receive approximately 25% of the cardiac output
- Approximately 180 litres of filtrate are produced each day
- Many ions are also filtered e.g. sodium
- Over 99% of water and sodium are reabsorbed
How much Fluid and Solute is filtered/excreted/% reabsorbed in the Kidney?
Reabsorption of Fluid and Solute in the Kidney
What are the main processes involved in renal excretion?
Renal Excretion
The main processes involved in renal excretion are:
- Glomerular filtration
- Tubular secretion and reabsorption of drug and drug metabolites
- Can be by passive (simple) transfer or by active transport
What happens to drugs during glomerular filtration?
Which drugs do not pass into glomerular filtrate?
Glomerular Filtration
- Blood entering the glomerulus is under pressure and plasma is forced through pores in the capillary walls into the nephron (becomes the filtrate)
- The plasma forced through the pores in the capillary walls (filtrate) carries with it any free drug or free drug metabolites which are present
- Plasma proteins and blood cells are too large to pass through the pores and do not enter the filtrate
- Glomerular filtration enables drugs and their metabolites to move from the blood into the glomerular filtrate
- Most drugs and their metabolites pass very easily from the blood into the glomerular filtrate
- Exceptions are
- very large molecules
- drugs which are highly protein bound
What is the impact of protein binding on drug excretion?
Excretion - Protein Binding
- It is only the free drug which can move from the blood into the glomerular filtrate
- Drugs bound to plasma proteins e.g. albumin cannot be filtered
- Highly protein bound drugs are filtered slowly e.g. naproxen (99% protein binding)
- Some of the drug is always unbound, and naproxen is also metabolised
What are 3 examples of drugs that can be moved into or out of the renal tubules by carrier systems?
Renal Excretion - Carrier Systems
- Some drugs can also be moved into and out of the renal tubules by carrier systems
- This can be by facilitated diffusion, or by processes which require energy e.g. p- glycoprotein
- Examples of drugs moved by carrier systems include
- Digoxin
- Frusemide
- Penicillin
What is the clinical significance of drugs which aren’t metabolised or are metabolised into an active metabolite?
Renal Excretion
- Examples of drugs not metabolised include
- digoxin
- gentamicin
- An example of a drug which is metabolised to an active metabolite which is not further metabolised is
- allopurinol and the active metabolite oxypurinol
- If patients with renal impairment are taking these types of drugs, consideration must always be given to reducing the dose, or increasing the dosage interval, to avoid possible accumulation of the active drug/active metabolite in the body and adverse events
What are 2 ways of estimating renal function?
eGFR = Estimated Glomerular Filtration Rate
eGFR estimates renal function using the patient’s age, gender and serum creatinine level (weight is not included)
The Cockcroft-Gault equation is used to estimate creatinine clearance
- Creatinine clearance is an estimate of the glomerular filtration rate (GFR) and renal function
- The Cockcroft-Gault equation calculates creatinine clearance using the patient’s age, gender, serum creatinine level and weight
Difference with eGFR = weight included here
What is Creatinine?
Creatinine
- Creatinine is primarily produced by the metabolism of creatine phosphate which is used by skeletal muscle as an energy source
- Creatinine production is determined primarily by a person’s skeletal muscle mass
- Because the skeletal muscle mass in the body is relatively constant from day to day, the creatinine production normally remains essentially unchanged on a daily basis
How is Creatinine excreted and how does this make it a good approximation of GFR?
Creatinine and Creatinine Clearance
- Creatinine is not bound to plasma proteins and is excreted almost exclusively by glomerular filtration (it is secreted to a limited extent in the nephron)
- Because of this creatinine clearance is a good approximation of glomerular filtration rate (GFR) - it may overestimate by 10%
What are the 2 Cockcroft - Gault equations tht can be used to estimate renal function?
Cockcroft - Gault
Two Equations can be Used
What creatinine clearance value is associated with different degrees of renal impairment/failure?
How is it that a patient with significant renal impairment may still have a serum creatinine level within the normal range?
Creatinine Clearance - Elderly Patients
- Elderly patients have reduced skeletal muscle mass
- Their creatinine production is thus reduced
- Their kidneys do not have to handle a normal creatinine load
- An elderly patient with significant renal impairment may still have a serum creatinine level within the normal range
